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진단 데이터셋

진단 데이터셋

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● 데이터 상품명 진단 데이터셋 ● 데이터 상품 부제 COVID-19의 진단 관련 의학논문 데이터셋 ● 데이터 상품 요약 인용지수 상위 의학저널에 게재된 COVID-19의 진단에 관련된 의학 학술논문 데이터 ● 키워드 데이터셋 상품 정보 ■ 상품 설명 및 특징 - 의학논문의 저자 키워드, 초록, 제목 등에서 추출한 키워드에 키워드 속성, 대역어, 키워드 출처, 논문 DOI, 저자, 발행연월, 논문URL, 저널명, 저널 ISSN, 발행기관, Impact Factor의 정보를 매핑한 데이터 ■ 컬럼(속성) 정보 - 키워드명: 키워드 - 키워드속성: 키워드 성격 - 키워드출처: 키워드 출현 위치 - 키워드대역어: 자체 보유 의학사전 및 구글번역기에 의한 대역어 - 논문DOI명: 키워드 출현 논문의 DOI - 논문제목: 키워드 출현 논문의 제목 - 논문저자: 키워드 출현 논문의 저자 - 논문발행연월: 키워드 출현 논문의 발행연월 - 논문초록: 키워드 출현 논문의 초록 - 논문URL: 키워드 출현 논문의 URL - 저널ISSN명: 키워드 출현 논문의 저널 ISSN - 저널제목: 키워드 출현 논문의 저널명 - 저널발행기관명: 키워드 출현 논문의 발행기관명 ● 연관 데이터셋 상품 정보 ■ 상품 설명 및 특징 - 특정 키워드의 연관 키워드를 co-occurrence기법과 Latent Semantic Algorithm에 의해 추출한 데이터셋 ■ 컬럼(속성) 정보 - 키워드명: 키워드 - 키워드속성: 키워드의 성격 - 연관키워드명: 키워드와 연관된 키워드 - 연관키워드 속성: 연관키워드의 속성 - 연관중요도: 동의여 여부와 동시출현수를 지표로 하는 중요도 ● 기간 및 범위 - 2014년 5월 ~ 2022년 12월 ● 활용 예제 - 특정 주제에 해당되는 키워드의 속성별, 저널별, 연도별, 저자별 추이 - 키워드의 연관어를 속성별, 저널별, 연도별, 저자별 분석

샘플정보
ID
카테고리ID
카테고리명
키워드명
키워드속성
대체키워드명
키워드출처
키워드대역어
논문ID
논문DOI명
논문제목
논문저자
논문발행연월
논문유형
논문출처
논문초록
논문URL
저널ID
저널ISSN명
저널제목
저널발행기관명
저널ImpactFactor명
1107828 897 진단 antibody combination Term antibody combination title None 23345 10.1016/j.kint.2022.01.016 Breakthrough omicron COVID-19 infections in patients receiving the REGEN-Cov antibody combination Adrien Flahault@@@Justine Touchard@@@H?l?ne P?r?@@@Laetitia Ulrich@@@Brigitte Sabatier@@@David Veyer@@@David Lebeaux@@@Eric Thervet 202204 Article PMC None https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837470/ 1008 0085-2538 Kidney international New York : Elsevier.
1212300 897 진단 variant Term variant title 변형 11586 10.1038/s41422-022-00631-z A pan-sarbecovirus vaccine induces highly potent and durable neutralizing antibody responses in non-human primates against SARS-CoV-2 Omicron variant Zezhong Liu@@@Jasper Fuk-Woo Chan@@@Jie Zhou@@@Meiyu Wang@@@Qian Wang@@@Guangxu Zhang@@@Wei Xu@@@Kenn Ka-Heng Chik@@@Yilong Zhang@@@Youchun Wang@@@Kwok-Yung Yuen@@@Lu Lu@@@Shibo Jiang 202205 Article PMC None https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866927/ 114 1001-0602 Cell Research Basingstoke, England : Nature Publishing Group.
1212288 897 진단 severe acute respiratory syndrome coronavirus 2 Virus severe acute respiratory syndrome coronavirus 2 author 심한 급성 호흡기 증후군 코로나 바이러스 2 9506 10.3201/eid2704.204200 Increased SARS-CoV-2 Testing Capacity with Pooled Saliva Samples 202104 Dispatch PMC We analyzed feasibility of pooling saliva samples for severe acute respiratory syndrome coronavirus 2 testing and found that sensitivity decreased according to pool size: 5 samples/pool, 7.4% reduction; 10 samples/pool, 11.1%; and 20 samples/pool, 14.8%. When virus prevalence is >2.6%, pools of 5 require fewer tests; when <0.6%, pools of 20 support screening strategies . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007323/ 4 1080-6040 Emerging Infectious Diseases Atlanta, GA : National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) 3.67000
1212289 897 진단 Support Term support abstract None 9506 10.3201/eid2704.204200 Increased SARS-CoV-2 Testing Capacity with Pooled Saliva Samples 202104 Dispatch PMC We analyzed feasibility of pooling saliva samples for severe acute respiratory syndrome coronavirus 2 testing and found that sensitivity decreased according to pool size: 5 samples/pool, 7.4% reduction; 10 samples/pool, 11.1%; and 20 samples/pool, 14.8%. When virus prevalence is >2.6%, pools of 5 require fewer tests; when <0.6%, pools of 20 support screening strategies . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007323/ 4 1080-6040 Emerging Infectious Diseases Atlanta, GA : National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) 3.67000
1212290 897 진단 Testing Term testing title 검사하기 9506 10.3201/eid2704.204200 Increased SARS-CoV-2 Testing Capacity with Pooled Saliva Samples 202104 Dispatch PMC We analyzed feasibility of pooling saliva samples for severe acute respiratory syndrome coronavirus 2 testing and found that sensitivity decreased according to pool size: 5 samples/pool, 7.4% reduction; 10 samples/pool, 11.1%; and 20 samples/pool, 14.8%. When virus prevalence is >2.6%, pools of 5 require fewer tests; when <0.6%, pools of 20 support screening strategies . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007323/ 4 1080-6040 Emerging Infectious Diseases Atlanta, GA : National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) 3.67000
1212291 897 진단 virus Term virus abstract 바이러스 9506 10.3201/eid2704.204200 Increased SARS-CoV-2 Testing Capacity with Pooled Saliva Samples 202104 Dispatch PMC We analyzed feasibility of pooling saliva samples for severe acute respiratory syndrome coronavirus 2 testing and found that sensitivity decreased according to pool size: 5 samples/pool, 7.4% reduction; 10 samples/pool, 11.1%; and 20 samples/pool, 14.8%. When virus prevalence is >2.6%, pools of 5 require fewer tests; when <0.6%, pools of 20 support screening strategies . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007323/ 4 1080-6040 Emerging Infectious Diseases Atlanta, GA : National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) 3.67000
1212292 897 진단 viruses Term virus author 바이러스 9506 10.3201/eid2704.204200 Increased SARS-CoV-2 Testing Capacity with Pooled Saliva Samples 202104 Dispatch PMC We analyzed feasibility of pooling saliva samples for severe acute respiratory syndrome coronavirus 2 testing and found that sensitivity decreased according to pool size: 5 samples/pool, 7.4% reduction; 10 samples/pool, 11.1%; and 20 samples/pool, 14.8%. When virus prevalence is >2.6%, pools of 5 require fewer tests; when <0.6%, pools of 20 support screening strategies . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007323/ 4 1080-6040 Emerging Infectious Diseases Atlanta, GA : National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) 3.67000
1212293 897 진단 zoonoses Disease zoonose author zoonoses 9506 10.3201/eid2704.204200 Increased SARS-CoV-2 Testing Capacity with Pooled Saliva Samples 202104 Dispatch PMC We analyzed feasibility of pooling saliva samples for severe acute respiratory syndrome coronavirus 2 testing and found that sensitivity decreased according to pool size: 5 samples/pool, 7.4% reduction; 10 samples/pool, 11.1%; and 20 samples/pool, 14.8%. When virus prevalence is >2.6%, pools of 5 require fewer tests; when <0.6%, pools of 20 support screening strategies . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007323/ 4 1080-6040 Emerging Infectious Diseases Atlanta, GA : National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) 3.67000
1212294 897 진단 induce Action induce title None 11586 10.1038/s41422-022-00631-z A pan-sarbecovirus vaccine induces highly potent and durable neutralizing antibody responses in non-human primates against SARS-CoV-2 Omicron variant Zezhong Liu@@@Jasper Fuk-Woo Chan@@@Jie Zhou@@@Meiyu Wang@@@Qian Wang@@@Guangxu Zhang@@@Wei Xu@@@Kenn Ka-Heng Chik@@@Yilong Zhang@@@Youchun Wang@@@Kwok-Yung Yuen@@@Lu Lu@@@Shibo Jiang 202205 Article PMC None https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866927/ 114 1001-0602 Cell Research Basingstoke, England : Nature Publishing Group.
1123474 897 진단 Evidence Term evidence abstract None 23917 10.1016/j.cmi.2021.10.018 Signals were broadly positive for months, but never definitive: the tocilizumab story Alessandro Cozzi-Lepri@@@Colette Smith@@@Cristina Mussini 202203 Review PMC {{{ Abstract }}} !!{{ Background: }} Most treatment guidelines for coronavirus disease 2019 (COVID-19) currently recommend tocilizumab in combination with dexamethasone in critically ill patients who are exhibiting rapid respiratory decompensation. !!{{ Aims: }} To produce a critical review and summary of the pathway which led to the repurposing of tocilizumab for COVID-19 treatment, from in vitro observations to guidelines recommendations. !!{{ Sources: }} All studies evaluating the effectiveness of tocilizumab to treat COVID-19 disease published between July 2020 and July 2021. !!{{ Content: }} Two large and methodologically well conducted observational studies, the TESEO and the STOP COVID cohorts, showed a reduction in the risk of invasive mechanical ventilation or death in patients treated with tocilizumab as compared to standard of care in 2020. Concomitantly, and up to February 2021, a number of randomized trials (RCTs) with small sample sizes were showing discrepant results. These RCTs had a number of issues: small sample size, various designs and inclusion criteria, and different dosages of tocilizumab used. The confidence interval of the meta-analytic estimate for the RCT results was consistent with the hypothesis of no efficacy of tocilizumab. In our opinion, this was mainly because the meta-analysis included small and heterogeneous studies. These results led to a delay in the inclusion of tocilizumab in guidelines which occurred only in the summer of 2021. !!{{ Implications: }} Although observational studies are unable to control for unmeasured confounding, they can be put together quickly during a pandemic and promptly provide important information. The large sample size allows us to investigate effect measure modifiers and to better target interventions. It is key that the effect size is somewhat large (RR &gt; 2), all sources of bias are properly accounted for, and the direct evidence is weighted against these factors. It appears to us that for tocilizumab, not having dismissed the results of carefully designed and analysed observational studies in 2020 could have prevented many deaths over those months. !!{{ Keywords: }} Covid-19; Evidence-based medicine; Meta-analysis; Propensity score methods; Tocilizumab. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576060/ 884 1198-743X Clinical microbiology and infection : the official London : Elsevier. 3.11100
1112511 897 진단 ranged Action ranged abstract None 23513 10.1080/23744235.2020.1871066 A systematic review on the recurrence of SARS-CoV-2 virus: frequency, risk factors, and possible explanations Seyed Mohammad Piri@@@Maryam Edalatfar@@@Sina Shool@@@Mohammad Naser Jalalian@@@Soheil Tavakolpour 202105 Article PMC {{{ Abstract }}} !!{{ Background: }} Since late 2019, SARS-CoV-2 which leads to coronavirus disease 2019 (COVID-19), has caused thousands of deaths. There are some pieces of evidence that SARS-CoV-2 genome could be re-detectable in recovered patients. !!{{ Methods: }} We performed a systematic review in the PubMed/Medline database to address the risk of SARS-CoV-2 recurrence. The last update was for 20 November 2020. Among the 1178 initially found articles, 66 met the inclusion criteria and were considered. !!{{ Findings: }} In total, 1128 patients with at least one-time recurrence of SARS-CoV-2 were included. Recurrence rate has been reported between 2.3% and 21.4% in cohort studies, within a mean of 20 (ranged 1-98) days after discharge; younger patients are being affected more. Following the second course of disease, the disease severity decreased or remained unchanged in 97.3% while it increased in 2.6%. Anti-SARS-CoV-2 IgG and IgM were positive in 11-95% and 58.8-100%, respectively. Based on the literature, three possibilities include reactivation of previous disease, reinfection with the same virus, and false negative, which have been discussed in details. !!{{ Conclusion: }} There is a relatively notable risk of disease recurrence in previously recovered patients, even those who are immunised against the virus. More studies are required to clarify the underlying cause of this phenomenon. !!{{ Keywords: }} COVID-19; Coronavirus; PCR; SARS-CoV-2; recurrence; systematic review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852280/ 1028 2374-4235 Infectious diseases (London, England) London, England : Informa Healthcare
1115011 897 진단 age Term age abstract 오랫동안 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1114984 897 진단 randomised Term randomised title,abstract 무작위 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114985 897 진단 Randomly Term randomly abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114986 897 진단 recalled Action recalled abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114987 897 진단 receive Action receive abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114988 897 진단 Registered Action registered abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114989 897 진단 reported Action reported abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1107959 897 진단 Characteristics Term characteristic abstract 특징 23334 10.3389/fimmu.2022.770982 Evaluation of Spike Protein Epitopes by Assessing the Dynamics of Humoral Immune Responses in Moderate COVID-19 Lingyun Chen@@@Pengfei Pang@@@Huan Qi@@@Keqiang Yan@@@Yan Ren@@@Mingliang Ma@@@Ruyin Cao@@@Hua Li@@@Chuansheng Hu@@@Yang Li@@@Jun Xia@@@Danyun Lai@@@Yuliang Dong@@@Hewei Jiang@@@Hainan Zhang@@@Hong Shan@@@Shengce Tao@@@Siqi Liu 202203 Article PMC {{{ Abstract }}} !! The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike protein (S) of SARS-CoV-2 is a major target for diagnosis and vaccine development because of its essential role in viral infection and host immunity. Currently, time-dependent responses of humoral immune system against various S protein epitopes are poorly understood. In this study, enzyme-linked immunosorbent assay (ELISA), peptide microarray, and antibody binding epitope mapping (AbMap) techniques were used to systematically analyze the dynamic changes of humoral immune responses against the S protein in a small cohort of moderate COVID-19 patients who were hospitalized for approximately two months after symptom onset. Recombinant truncated S proteins, target S peptides, and random peptides were used as antigens in the analyses. The assays demonstrated the dynamic IgM- and IgG recognition and reactivity against various S protein epitopes with patient-dependent patterns. Comprehensive analysis of epitope distribution along the spike gene sequence and spatial structure of the homotrimer S protein demonstrated that most IgM- and IgG-reactive peptides were clustered into similar genomic regions and were located at accessible domains. Seven S peptides were generally recognized by IgG antibodies derived from serum samples of all COVID-19 patients. The dynamic immune recognition signals from these seven S peptides were comparable to those of the entire S protein or truncated S1 protein. This suggested that the humoral immune system recognized few conserved S protein epitopes in most COVID-19 patients during the entire duration of humoral immune response after symptom onset. Furthermore, in this cohort, individual patients demonstrated stable immune recognition to certain S protein epitopes throughout their hospitalization period. Therefore, the dynamic characteristics of humoral immune responses to S protein have provided valuable information for accurate diagnosis and immunotherapy of COVID-19 patients. !!{{ Keywords: }} AbMap; COVID-19; ELISA; S protein; SARS-CoV-2; dynamics; epitope; microarray. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971992/ 109 1664-3224 Frontiers in Immunology [Lausanne : Frontiers Research Foundation].
1123464 897 진단 COVID-19 disease Disease covid-19 disease abstract Covid-19 질병 23917 10.1016/j.cmi.2021.10.018 Signals were broadly positive for months, but never definitive: the tocilizumab story Alessandro Cozzi-Lepri@@@Colette Smith@@@Cristina Mussini 202203 Review PMC {{{ Abstract }}} !!{{ Background: }} Most treatment guidelines for coronavirus disease 2019 (COVID-19) currently recommend tocilizumab in combination with dexamethasone in critically ill patients who are exhibiting rapid respiratory decompensation. !!{{ Aims: }} To produce a critical review and summary of the pathway which led to the repurposing of tocilizumab for COVID-19 treatment, from in vitro observations to guidelines recommendations. !!{{ Sources: }} All studies evaluating the effectiveness of tocilizumab to treat COVID-19 disease published between July 2020 and July 2021. !!{{ Content: }} Two large and methodologically well conducted observational studies, the TESEO and the STOP COVID cohorts, showed a reduction in the risk of invasive mechanical ventilation or death in patients treated with tocilizumab as compared to standard of care in 2020. Concomitantly, and up to February 2021, a number of randomized trials (RCTs) with small sample sizes were showing discrepant results. These RCTs had a number of issues: small sample size, various designs and inclusion criteria, and different dosages of tocilizumab used. The confidence interval of the meta-analytic estimate for the RCT results was consistent with the hypothesis of no efficacy of tocilizumab. In our opinion, this was mainly because the meta-analysis included small and heterogeneous studies. These results led to a delay in the inclusion of tocilizumab in guidelines which occurred only in the summer of 2021. !!{{ Implications: }} Although observational studies are unable to control for unmeasured confounding, they can be put together quickly during a pandemic and promptly provide important information. The large sample size allows us to investigate effect measure modifiers and to better target interventions. It is key that the effect size is somewhat large (RR &gt; 2), all sources of bias are properly accounted for, and the direct evidence is weighted against these factors. It appears to us that for tocilizumab, not having dismissed the results of carefully designed and analysed observational studies in 2020 could have prevented many deaths over those months. !!{{ Keywords: }} Covid-19; Evidence-based medicine; Meta-analysis; Propensity score methods; Tocilizumab. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576060/ 884 1198-743X Clinical microbiology and infection : the official London : Elsevier. 3.11100
1112874 897 진단 approache Action approache abstract None 23527 10.14283/jfa.2020.41 Say Ninetynine: It's Never too Late to Recover from COVID-19 M Tosato@@@F Varone@@@A Ciccullo@@@R Calvani@@@D Moschese@@@A Potenza@@@M Siciliano@@@M Fantoni 202101 Case Reports PMC {{{ Abstract }}} !! COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, showed higher severity and lethality in male older adults . There are currently no specific treatments. Studies are evaluating the efficacy of monoclonal antibodies against interleukin-6 receptor. Here we present the case of a 98-years old man admitted to our COVID-Hospital with acute respiratory failure. Comprehensive geriatric assessment showed no signs of frailty. First-line therapy with hydroxychloroquine and anticoagulants was not effective. Patient was administered intravenous monoclonal antibodies, and he showed remarkable clinical improvement. This case suggests that age alone should not preclude access to new therapeutic approaches. Comprehensive, multisciplinary, multidomain approaches are needed to develop patient-tailored treatments against COVID-19. !!{{ Keywords: }} Frailty; aging; comprehensive geriatric assesment; covid-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412775/ 740 2260-1341 The Journal of Frailty & Aging Toulouse : Serdi Edition.
1112926 897 진단 IgG anti-spike antibody Term igg anti-spike antibody abstract None 23532 10.5144/0256-4947.2022.69 Seroprevalence of SARS-Cov-2 IgG antibodies in patients at a single center in Saudi Arabia Waleed H Mahallawi@@@Mohammad A Alsarani@@@Rami H Aljohani@@@Abdulrahman A Alluhaibi@@@Turki H Alamri@@@Nadir A Ibrahim@@@Khalid H Mahallawi@@@Omar F Khabourd 202203 Article PMC {{{ Abstract }}} !!{{ Background: }} The coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on public health as well as the economy. Understanding the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among undiagnosed individuals is important for developing an informed pandemic response. !!{{ Objective: }} Investigate the prevalence of undiagnosed COVID-19 disease. !!{{ Design: }} Cross-sectional. !!{{ Setting: }} Tertiary care center in Madinah, Saudi Arabia. !!{{ Subjects and methods: }} All participants were on follow-up visits to various clinics and had not been previously diagnosed with COVID-19. Enzyme-linked immunosorbent assay was used to specifically assess the anti-spike IgG antibody seropositivity in serum samples. We associated the seropositivity rates of the participants with age, body mass index (BMI), nationality, blood groups, and sex with uni- and multivariate analyses. !!{{ Main outcome measures: }} Seropositivity for IgG anti-spike antibodies against SARS-CoV-2. !!{{ Sample size and characteristics: }} 527 subjects, with a median (interquartile percentiles) age of the 527 subjects was 34 (24-41). !!{{ Results: }} Of the 527 samples, about one-fourth (n=124, 23.5%) were positive for anti-spike IgG antibody against SARS CoV-2. Age was associated with anti-spike IgG antibody positivity ( P &lt;.002). Participants &gt;30 years were more likely to be seropositive (28-29%) than younger participants (15.4%). Additionally, seropositivity was associated with female gender ( P &lt;.001) and a higher BMI ( P &lt;.006). In the multivariate logistic regression, age &gt;30, female gender and BMI &gt;40 were associated with seropositivity. !!{{ Conclusion: }} The percentage of seropositive individuals reflects the high level of undiagnosed COVID-19 patients among the population. Our results will help in a better evaluation of the public health measures applied during the COVID-19 pandemic and any future public health crises. !!{{ Limitations: }} Sample size was small, single-center study and no rural areas were included. !!{{ Conflict of interest: }} None. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981997/ 1335 0256-4947 Annals of Saudi medicine Riyadh : King Faisal Specialist Hospital and Research Centre.
1112909 897 진단 body mass index Term body mass index abstract 체질량지수 23532 10.5144/0256-4947.2022.69 Seroprevalence of SARS-Cov-2 IgG antibodies in patients at a single center in Saudi Arabia Waleed H Mahallawi@@@Mohammad A Alsarani@@@Rami H Aljohani@@@Abdulrahman A Alluhaibi@@@Turki H Alamri@@@Nadir A Ibrahim@@@Khalid H Mahallawi@@@Omar F Khabourd 202203 Article PMC {{{ Abstract }}} !!{{ Background: }} The coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on public health as well as the economy. Understanding the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among undiagnosed individuals is important for developing an informed pandemic response. !!{{ Objective: }} Investigate the prevalence of undiagnosed COVID-19 disease. !!{{ Design: }} Cross-sectional. !!{{ Setting: }} Tertiary care center in Madinah, Saudi Arabia. !!{{ Subjects and methods: }} All participants were on follow-up visits to various clinics and had not been previously diagnosed with COVID-19. Enzyme-linked immunosorbent assay was used to specifically assess the anti-spike IgG antibody seropositivity in serum samples. We associated the seropositivity rates of the participants with age, body mass index (BMI), nationality, blood groups, and sex with uni- and multivariate analyses. !!{{ Main outcome measures: }} Seropositivity for IgG anti-spike antibodies against SARS-CoV-2. !!{{ Sample size and characteristics: }} 527 subjects, with a median (interquartile percentiles) age of the 527 subjects was 34 (24-41). !!{{ Results: }} Of the 527 samples, about one-fourth (n=124, 23.5%) were positive for anti-spike IgG antibody against SARS CoV-2. Age was associated with anti-spike IgG antibody positivity ( P &lt;.002). Participants &gt;30 years were more likely to be seropositive (28-29%) than younger participants (15.4%). Additionally, seropositivity was associated with female gender ( P &lt;.001) and a higher BMI ( P &lt;.006). In the multivariate logistic regression, age &gt;30, female gender and BMI &gt;40 were associated with seropositivity. !!{{ Conclusion: }} The percentage of seropositive individuals reflects the high level of undiagnosed COVID-19 patients among the population. Our results will help in a better evaluation of the public health measures applied during the COVID-19 pandemic and any future public health crises. !!{{ Limitations: }} Sample size was small, single-center study and no rural areas were included. !!{{ Conflict of interest: }} None. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981997/ 1335 0256-4947 Annals of Saudi medicine Riyadh : King Faisal Specialist Hospital and Research Centre.
1112875 897 진단 caused Action caused abstract None 23527 10.14283/jfa.2020.41 Say Ninetynine: It's Never too Late to Recover from COVID-19 M Tosato@@@F Varone@@@A Ciccullo@@@R Calvani@@@D Moschese@@@A Potenza@@@M Siciliano@@@M Fantoni 202101 Case Reports PMC {{{ Abstract }}} !! COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, showed higher severity and lethality in male older adults . There are currently no specific treatments. Studies are evaluating the efficacy of monoclonal antibodies against interleukin-6 receptor. Here we present the case of a 98-years old man admitted to our COVID-Hospital with acute respiratory failure. Comprehensive geriatric assessment showed no signs of frailty. First-line therapy with hydroxychloroquine and anticoagulants was not effective. Patient was administered intravenous monoclonal antibodies, and he showed remarkable clinical improvement. This case suggests that age alone should not preclude access to new therapeutic approaches. Comprehensive, multisciplinary, multidomain approaches are needed to develop patient-tailored treatments against COVID-19. !!{{ Keywords: }} Frailty; aging; comprehensive geriatric assesment; covid-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412775/ 740 2260-1341 The Journal of Frailty & Aging Toulouse : Serdi Edition.
1114990 897 진단 resulting Action resulting abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1107956 897 진단 Assessing Term assessing title None 23334 10.3389/fimmu.2022.770982 Evaluation of Spike Protein Epitopes by Assessing the Dynamics of Humoral Immune Responses in Moderate COVID-19 Lingyun Chen@@@Pengfei Pang@@@Huan Qi@@@Keqiang Yan@@@Yan Ren@@@Mingliang Ma@@@Ruyin Cao@@@Hua Li@@@Chuansheng Hu@@@Yang Li@@@Jun Xia@@@Danyun Lai@@@Yuliang Dong@@@Hewei Jiang@@@Hainan Zhang@@@Hong Shan@@@Shengce Tao@@@Siqi Liu 202203 Article PMC {{{ Abstract }}} !! The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike protein (S) of SARS-CoV-2 is a major target for diagnosis and vaccine development because of its essential role in viral infection and host immunity. Currently, time-dependent responses of humoral immune system against various S protein epitopes are poorly understood. In this study, enzyme-linked immunosorbent assay (ELISA), peptide microarray, and antibody binding epitope mapping (AbMap) techniques were used to systematically analyze the dynamic changes of humoral immune responses against the S protein in a small cohort of moderate COVID-19 patients who were hospitalized for approximately two months after symptom onset. Recombinant truncated S proteins, target S peptides, and random peptides were used as antigens in the analyses. The assays demonstrated the dynamic IgM- and IgG recognition and reactivity against various S protein epitopes with patient-dependent patterns. Comprehensive analysis of epitope distribution along the spike gene sequence and spatial structure of the homotrimer S protein demonstrated that most IgM- and IgG-reactive peptides were clustered into similar genomic regions and were located at accessible domains. Seven S peptides were generally recognized by IgG antibodies derived from serum samples of all COVID-19 patients. The dynamic immune recognition signals from these seven S peptides were comparable to those of the entire S protein or truncated S1 protein. This suggested that the humoral immune system recognized few conserved S protein epitopes in most COVID-19 patients during the entire duration of humoral immune response after symptom onset. Furthermore, in this cohort, individual patients demonstrated stable immune recognition to certain S protein epitopes throughout their hospitalization period. Therefore, the dynamic characteristics of humoral immune responses to S protein have provided valuable information for accurate diagnosis and immunotherapy of COVID-19 patients. !!{{ Keywords: }} AbMap; COVID-19; ELISA; S protein; SARS-CoV-2; dynamics; epitope; microarray. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971992/ 109 1664-3224 Frontiers in Immunology [Lausanne : Frontiers Research Foundation].
1114243 897 진단 participant Patient participant abstract None 23573 10.1186/s12889-022-13464-7 Seroprevalence of SARS-CoV-2 antibody among urban Iranian population: findings from the second large population-based cross-sectional study Mohammad Zamani@@@Hossein Poustchi@@@Zahra Mohammadi@@@Sahar Dalvand@@@Maryam Sharafkhah@@@Seyed Abbas Motevalian@@@Saeid Eslami@@@Amir Emami@@@Mohammad Hossein Somi@@@Jamshid Yazdani-Charati@@@Nader Saki@@@Manoochehr Karami@@@Farid Najafi@@@Iraj Mohebbi@@@Nasrollah Veisi@@@Ahmad Hormati@@@Farhad Pourfarzi@@@Reza Ghadimi@@@Alireza Ansari-Moghaddam@@@Hamid Sharifi@@@Gholamreza Roshandel@@@Fariborz Mansour-Ghanaei@@@Farahnaz Joukar@@@Amaneh Shayanrad@@@Sareh Eghtesad@@@Ahmadreza Niavarani@@@Alireza Delavari@@@Soudeh Kaveh@@@Akbar Feizesani@@@Melineh Markarian@@@Fatemeh Shafighian@@@Alireza Sadjadi@@@Maryam Darvishian@@@Reza Malekzadeh 202205 Article PMC {{{ Abstract }}} !!{{ Background: }} The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. !!{{ Methods: }} This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. !!{{ Results: }} The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. !!{{ Conclusions: }} Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021. !!{{ Keywords: }} COVID-19; General population; Infection; SARS-CoV-2; Seroprevalence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125542/ 28 2474-7629 BMC Public Health London : BioMed Central
1113945 897 진단 RPR Term rpr author None 23563 10.1093/ajcp/aqac025 COVID-19 mRNA Vaccines May Cause False Reactivity in Some Serologic Laboratory Tests, Including Rapid Plasma Reagin Tests Dimitrios Korentzelos@@@Vandana Baloda@@@Yujung Jung@@@Bradley Wheeler@@@Michael R Shurin@@@Sarah E Wheeler 202208 Article PMC {{{ Abstract }}} !!{{ Objectives: }} Acute viral infections and some vaccines have been shown to increase false positivity in serologic assays. We assessed if the messenger RNA coronavirus disease 2019 (COVID-19) vaccines could cause false reactivity in common serologic assays in a pilot longitudinal cohort. !!{{ Methods: }} Thirty-eight participants with sera available prevaccination, 2 weeks after each vaccine dose, and monthly thereafter for up to 5 months were tested for common infectious disease serologies and antiphospholipid syndrome (APS) serology markers on the BioPlex 2200, Sure-Vue rapid plasma reagin (RPR), and Macro-Vue RPR. Twenty-two participants received the Moderna vaccine and 16 received the Pfizer vaccine. !!{{ Results: }} Most assays had no change in reactivity over the course of the sample draws, including APS markers. Epstein-Barr virus immunoglobulin G (IgG), measles IgG, and rubella immunoglobulin M all had possible false reactivity in one to two participants. RPR tests demonstrated false reactivity, with baseline nonreactive participant samples becoming reactive following vaccination. There were more false reactive participants (7/38) in the BioPlex RPR than in the Sure-Vue (2/38) and Macro-Vue (1/38) tests. All falsely reactive RPR tests were in participants who received the Moderna vaccine. !!{{ Conclusions: }} Serologic assays with results that do not fit the clinical picture following COVID-19 vaccination should be repeated. Effects of false reactivity can last more than 5 months in some assays. In particular, RPR is susceptible to false reactivity, and there is variability among assays. Larger longitudinal studies are needed to determine the incidence and window of false reactivity. !!{{ Keywords: }} COVID-19 vaccine; RPR; Serology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992293/ 327 0002-9173 American journal of clinical pathology Oxford : Oxford University Press.
1113946 897 진단 sera Term sera abstract 혈청 23563 10.1093/ajcp/aqac025 COVID-19 mRNA Vaccines May Cause False Reactivity in Some Serologic Laboratory Tests, Including Rapid Plasma Reagin Tests Dimitrios Korentzelos@@@Vandana Baloda@@@Yujung Jung@@@Bradley Wheeler@@@Michael R Shurin@@@Sarah E Wheeler 202208 Article PMC {{{ Abstract }}} !!{{ Objectives: }} Acute viral infections and some vaccines have been shown to increase false positivity in serologic assays. We assessed if the messenger RNA coronavirus disease 2019 (COVID-19) vaccines could cause false reactivity in common serologic assays in a pilot longitudinal cohort. !!{{ Methods: }} Thirty-eight participants with sera available prevaccination, 2 weeks after each vaccine dose, and monthly thereafter for up to 5 months were tested for common infectious disease serologies and antiphospholipid syndrome (APS) serology markers on the BioPlex 2200, Sure-Vue rapid plasma reagin (RPR), and Macro-Vue RPR. Twenty-two participants received the Moderna vaccine and 16 received the Pfizer vaccine. !!{{ Results: }} Most assays had no change in reactivity over the course of the sample draws, including APS markers. Epstein-Barr virus immunoglobulin G (IgG), measles IgG, and rubella immunoglobulin M all had possible false reactivity in one to two participants. RPR tests demonstrated false reactivity, with baseline nonreactive participant samples becoming reactive following vaccination. There were more false reactive participants (7/38) in the BioPlex RPR than in the Sure-Vue (2/38) and Macro-Vue (1/38) tests. All falsely reactive RPR tests were in participants who received the Moderna vaccine. !!{{ Conclusions: }} Serologic assays with results that do not fit the clinical picture following COVID-19 vaccination should be repeated. Effects of false reactivity can last more than 5 months in some assays. In particular, RPR is susceptible to false reactivity, and there is variability among assays. Larger longitudinal studies are needed to determine the incidence and window of false reactivity. !!{{ Keywords: }} COVID-19 vaccine; RPR; Serology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992293/ 327 0002-9173 American journal of clinical pathology Oxford : Oxford University Press.
1113947 897 진단 serologic Term serologic title,abstract 혈청 학적 23563 10.1093/ajcp/aqac025 COVID-19 mRNA Vaccines May Cause False Reactivity in Some Serologic Laboratory Tests, Including Rapid Plasma Reagin Tests Dimitrios Korentzelos@@@Vandana Baloda@@@Yujung Jung@@@Bradley Wheeler@@@Michael R Shurin@@@Sarah E Wheeler 202208 Article PMC {{{ Abstract }}} !!{{ Objectives: }} Acute viral infections and some vaccines have been shown to increase false positivity in serologic assays. We assessed if the messenger RNA coronavirus disease 2019 (COVID-19) vaccines could cause false reactivity in common serologic assays in a pilot longitudinal cohort. !!{{ Methods: }} Thirty-eight participants with sera available prevaccination, 2 weeks after each vaccine dose, and monthly thereafter for up to 5 months were tested for common infectious disease serologies and antiphospholipid syndrome (APS) serology markers on the BioPlex 2200, Sure-Vue rapid plasma reagin (RPR), and Macro-Vue RPR. Twenty-two participants received the Moderna vaccine and 16 received the Pfizer vaccine. !!{{ Results: }} Most assays had no change in reactivity over the course of the sample draws, including APS markers. Epstein-Barr virus immunoglobulin G (IgG), measles IgG, and rubella immunoglobulin M all had possible false reactivity in one to two participants. RPR tests demonstrated false reactivity, with baseline nonreactive participant samples becoming reactive following vaccination. There were more false reactive participants (7/38) in the BioPlex RPR than in the Sure-Vue (2/38) and Macro-Vue (1/38) tests. All falsely reactive RPR tests were in participants who received the Moderna vaccine. !!{{ Conclusions: }} Serologic assays with results that do not fit the clinical picture following COVID-19 vaccination should be repeated. Effects of false reactivity can last more than 5 months in some assays. In particular, RPR is susceptible to false reactivity, and there is variability among assays. Larger longitudinal studies are needed to determine the incidence and window of false reactivity. !!{{ Keywords: }} COVID-19 vaccine; RPR; Serology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992293/ 327 0002-9173 American journal of clinical pathology Oxford : Oxford University Press.
1123053 897 진단 searched Action searched abstract None 23895 10.1016/j.cmi.2021.08.016 Tocilizumab for coronavirus disease 2019 in pregnancy and lactation: a narrative review Sarah C J Jorgensen@@@Stephen E Lapinsky 202201 Review PMC {{{ Abstract }}} !!{{ Background: }} Tocilizumab is a monoclonal antibody that interrupts interleukin-6 signalling, reducing downstream effects on inflammation and the innate immune response. It was shown to reduce mortality in patients with severe or critical coronavirus disease 2019 (COVID-19). Pregnant and breastfeeding people were largely excluded from clinical trials and hence, the extent to which results can be applied to these populations is not clear. !!{{ Objectives: }} To synthesize published data on tocilizumab in pregnancy and lactation, highlight important knowledge gaps, and help inform clinical decision-making about tocilizumab's use in these populations with COVID-19. !!{{ Sources: }} PubMed was searched for studies evaluating tocilizumab in pregnancy and lactation for COVID-19 and other indications. Literature on pharmacokinetics and reproductive/fetal safety of monoclonal antibodies in general was also sought. The US Food and Drug Administration and the European Medicines Agency guidance for the industry and regulatory approval documents were reviewed. !!{{ Content: }} Published data on tocilizumab in pregnancy include 610 cases (n = 20 with COVID-19) together with seven mother-infant breastfeeding pairs. Higher rates of spontaneous abortion and premature birth have been reported compared with the general population, but multiple confounding variables limit interpretation. There is little data on tocilizumab exposure in the second and third trimesters when transplacental transport is highest. The effects of tocilizumab on the developing immune system are unclear. Pregnant patients with COVID-19 who received tocilizumab were often critically ill and corticosteroid use was uncommon. Neonatal follow up was limited. Tocilizumab appears to be compatible with breastfeeding. !!{{ Implications: }} Although the available data do not raise serious safety signals, they have significant limitations and are not sufficient to delineate the complete spectrum of potential adverse outcomes that may be associated with tocilizumab exposure during pregnancy and lactation. Diligent follow up and documentation of pregnancy outcomes will be important moving forward. A more effective regulatory framework to ensure equitable inclusion of pregnant people in research is clearly needed. !!{{ Keywords: }} Breastfeeding; COVID-19; Lactation; Pregnancy; SARS-CoV-2; Tocilizumab. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381634/ 884 1198-743X Clinical microbiology and infection : the official London : Elsevier. 3.11100
1108421 897 진단 evaluated Action evaluated abstract None 23349 10.1016/j.jim.2022.113243 Clinical and analytical evaluation of the Abbott AdviseDx quantitative SARS-CoV-2 IgG assay and comparison with two other serological tests Gabriel N Maine@@@Subhashree Mallika Krishnan@@@Kelly Walewski@@@Jillian Trueman@@@Elizabeth Sykes@@@Qian Sun 202204 Article PMC {{{ Abstract }}} !!{{ Introduction: }} Serological testing is an important tool to assist with assessing the immune response to SARS-CoV-2 infections, the causative agent of COVID-19. A quantitative assay was recently developed by Abbott Laboratories to measures antibodies against the receptor binding domain of the spike protein. In addition to assessing disease prevalence, this assay is useful towards determining the scale and duration of the humoral response to infection and vaccination. Here we evaluated the clinical and analytical performance of the quantitative Abbott AdviseDx SARS-CoV-2 IgG II assay and characterized the longitudinal dynamics of the IgG response against SARS-CoV-2 in 402 infected individuals up to 322 days post-symptom onset. !!{{ Methods: }} To assess test sensitivity, 1257 serum specimens derived from 402 patients positive for SARS-CoV-2 by RT-PCR were analyzed on the Abbott Alinity platform. To evaluate test specificity, 394 specimens were tested from patients who were symptomatic but PCR negative for SARS-CoV-2, as well as 305 archived pre-pandemic samples. To further characterize test performance metrics, we evaluated assay precision and linearity. !!{{ Results: }} The Abbott AdviseDx SARS-CoV-2 IgG II assay exhibited diagnostic specificity of 99.02% using 305 pre - COVID-19 serum specimens and 98.73% using 394 PCR negative specimens. Using 1257 sequential serum samples collected from PCR-confirmed individuals, clinical test sensitivity of the assay was 39.7% at 3-7 days, 75.9% at 8-14 days, 95.6% at 15-21 days, and 98.7% at 4-5 weeks post-symptom onset. The assay is linear across the analytical measurement range claimed by the manufacturer (22-25,000 AU/mL) and exhibited good analytical precision. The median concentration of IgG increased steadily from &lt;22 AU/mL at 3-7 days post-symptom onset, to a peak of 14,421 AU/mL at 6-7 weeks. Although antibody concentration started to decline at 8-9 weeks following symptom onset, all patients remained seropositive during the observation period. When the positivity rate of this assay was compared with the Abbott anti-NP IgG and EUROIMMUN anti-S1 IgG tests, clinical sensitivity of the Abbott AdviseDx SARS-CoV-2 IgG II assay was the highest at all time points with the exception of 4-5 weeks after symptom onset. !!{{ Conclusion: }} The Abbott AdviseDx SARS-CoV-2 IgG II assay offers high test specificity and sensitivity across a broad reportable range. We anticipate this assay will be a useful towards quantitatively assessing the humoral immune response to COVID-19 infection and vaccination. !!{{ Keywords: }} Abbott; Anti-RBD; Anti-spike; Coronavirus; SARS-CoV-2 IgG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847080/ 718 0022-1759 Journal of Immunological Methods Amsterdam : Elsevier.
1214317 897 진단 exclusion criteria Term exclusion criteria abstract 배제기준 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214318 897 진단 feedback Term feedback abstract 되먹임 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214319 897 진단 followed by Term followed by abstract None 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214320 897 진단 Follow-up Term follow-up abstract 추적 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214321 897 진단 gold Compound gold abstract 금 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214322 897 진단 gold standard Term gold standard abstract None 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214323 897 진단 Health Term health abstract 건강 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214324 897 진단 health resource Term health resource abstract None 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214325 897 진단 heart rate Term heart rate abstract 심박수 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214326 897 진단 incidence rates Term incidence rate abstract None 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214327 897 진단 Inclusion Term inclusion abstract abnormality 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1108109 897 진단 IgG1 Protein igg1 abstract None 23341 10.3389/fimmu.2022.878812 Brief Research Report: Virus-Specific Humoral Immunity at Admission Predicts the Development of Respiratory Failure in Unvaccinated SARS-CoV-2 Patients Ana Tajuelo@@@Octavio Carretero@@@Est?fani Garc?a-R?os@@@Mireia L?pez-Siles@@@Olga Cano@@@M?nica V?zquez@@@Vicente M?s@@@Isabel Rodr?guez-Goncer@@@Antonio Lalueza@@@Francisco L?pez-Medrano@@@Rafael San Juan@@@Mario Fern?ndez-Ruiz@@@Jos? M? Aguado@@@Michael J McConnell@@@Pilar P?rez-Romero 202204 Article PMC {{{ Abstract }}} !!{{ Introduction: }} There is robust evidence indicating that the SARS-CoV-2-specific humoral response is associated with protection against severe disease. However, relatively little data exist regarding how the humoral immune response at the time of hospital admission correlates with disease severity in unimmunized patients. Our goal was toidentify variables of the humoral response that could potentially serve as prognostic markers for COVID-19 progressionin unvaccinated SARS-CoV-2 patients. !!{{ Methods: }} A prospective cross-sectional study was carried out in a cohort of 160 unimmunized, adult COVID-19 patients from the Hospital Universitario 12Octubre. Participants were classified into four clinical groups based on disease severity: non-survivors with respiratory failure (RF), RF survivors, patients requiring oxygen therapy and those not receiving oxygen therapy. Serum samples were taken on admission and IgM, IgG, IgG subclass antibody titers were determined by ELISA, and neutralizing antibody titersusing a surrogate neutralization assay. The differences in the antibody titers between groups and the association between the clinical and analytical characteristics of the patients and the antibody titers were analyzed. !!{{ Results: }} Patients that developed RF and survived had IgM titers that were 2-fold higher than non-survivors ( p = 0.001), higher levels of total IgG than those who developed RF and succumbed to infection ( p &lt; 0.001), and than patients who required oxygen therapy ( p &lt; 0.05), and had 5-fold higher IgG1 titers than RF non-survivors ( p &lt; 0.001) and those who needed oxygen therapy ( p &lt; 0.001), and 2-fold higher than patients that did not require oxygen therapy during admission ( p &lt; 0.05). In contrast, RF non-survivorshad the lowest neutralizing antibodylevels, which were significantly lower compared those with RF that survived ( p = 0.03). A positive correlation was found between IgM, total IgG, IgG1 and IgG3 titers and neutralizing antibody titers in the total cohort (p ≤ 0.0036). !!{{ Conclusions: }} We demonstrate that patients with RF that survived infection had significantly higher IgM, IgG, IgG1 and neutralizing titers compared to patients with RF that succumb to infection, suggesting that using humoral response variables could be used as a prognostic marker for guiding the clinical management of unimmunized patients admitted to the hospital for SARS-CoV-2 infection. !!{{ Keywords: }} COVID disease severity; IgG; IgM 2; SARS-CoV-2; humoral response. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082065/ 109 1664-3224 Frontiers in Immunology [Lausanne : Frontiers Research Foundation].
1126072 897 진단 sequence similarity Term sequence similarity abstract None 24045 10.1021/acsinfecdis.1c00486 Microfluidic Antibody Affinity Profiling Reveals the Role of Memory Reactivation and Cross-Reactivity in the Defense Against SARS-CoV-2 Viola Denninger@@@Catherine K Xu@@@Georg Meisl@@@Alexey S Morgunov@@@Sebastian Fiedler@@@Alison Ilsley@@@Marc Emmenegger@@@Anisa Y Malik@@@Monika A Piziorska@@@Matthias M Schneider@@@Sean R A Devenish@@@Vasilis Kosmoliaptsis@@@Adriano Aguzzi@@@Heike Fiegler@@@Tuomas P J Knowles 202204 Article PMC {{{ Abstract }}} !! Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potentially beneficial and detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be reactivated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Determining the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be disentangled by surface-based assays like enzyme-linked immunosorbent assays (ELISAs), which are routinely used to assess cross-reactivity. Here, we have used microfluidic antibody affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high-affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory reactivation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2. !!{{ Keywords: }} SARS-CoV-2; antibody affinity; antibody concentration; antibody profiling; cross-reactivity; microfluidics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982494/ 565 2373-8227 ACS Infectious Diseases Washington, DC : ACS Publications
1126073 897 진단 sera Term sera abstract 혈청 24045 10.1021/acsinfecdis.1c00486 Microfluidic Antibody Affinity Profiling Reveals the Role of Memory Reactivation and Cross-Reactivity in the Defense Against SARS-CoV-2 Viola Denninger@@@Catherine K Xu@@@Georg Meisl@@@Alexey S Morgunov@@@Sebastian Fiedler@@@Alison Ilsley@@@Marc Emmenegger@@@Anisa Y Malik@@@Monika A Piziorska@@@Matthias M Schneider@@@Sean R A Devenish@@@Vasilis Kosmoliaptsis@@@Adriano Aguzzi@@@Heike Fiegler@@@Tuomas P J Knowles 202204 Article PMC {{{ Abstract }}} !! Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potentially beneficial and detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be reactivated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Determining the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be disentangled by surface-based assays like enzyme-linked immunosorbent assays (ELISAs), which are routinely used to assess cross-reactivity. Here, we have used microfluidic antibody affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high-affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory reactivation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2. !!{{ Keywords: }} SARS-CoV-2; antibody affinity; antibody concentration; antibody profiling; cross-reactivity; microfluidics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982494/ 565 2373-8227 ACS Infectious Diseases Washington, DC : ACS Publications
1126074 897 진단 seropositive Term seropositive abstract 혈청검사양성 24045 10.1021/acsinfecdis.1c00486 Microfluidic Antibody Affinity Profiling Reveals the Role of Memory Reactivation and Cross-Reactivity in the Defense Against SARS-CoV-2 Viola Denninger@@@Catherine K Xu@@@Georg Meisl@@@Alexey S Morgunov@@@Sebastian Fiedler@@@Alison Ilsley@@@Marc Emmenegger@@@Anisa Y Malik@@@Monika A Piziorska@@@Matthias M Schneider@@@Sean R A Devenish@@@Vasilis Kosmoliaptsis@@@Adriano Aguzzi@@@Heike Fiegler@@@Tuomas P J Knowles 202204 Article PMC {{{ Abstract }}} !! Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potentially beneficial and detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be reactivated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Determining the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be disentangled by surface-based assays like enzyme-linked immunosorbent assays (ELISAs), which are routinely used to assess cross-reactivity. Here, we have used microfluidic antibody affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high-affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory reactivation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2. !!{{ Keywords: }} SARS-CoV-2; antibody affinity; antibody concentration; antibody profiling; cross-reactivity; microfluidics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982494/ 565 2373-8227 ACS Infectious Diseases Washington, DC : ACS Publications
1126075 897 진단 severity Term severity abstract 중증도 24045 10.1021/acsinfecdis.1c00486 Microfluidic Antibody Affinity Profiling Reveals the Role of Memory Reactivation and Cross-Reactivity in the Defense Against SARS-CoV-2 Viola Denninger@@@Catherine K Xu@@@Georg Meisl@@@Alexey S Morgunov@@@Sebastian Fiedler@@@Alison Ilsley@@@Marc Emmenegger@@@Anisa Y Malik@@@Monika A Piziorska@@@Matthias M Schneider@@@Sean R A Devenish@@@Vasilis Kosmoliaptsis@@@Adriano Aguzzi@@@Heike Fiegler@@@Tuomas P J Knowles 202204 Article PMC {{{ Abstract }}} !! Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potentially beneficial and detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be reactivated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Determining the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be disentangled by surface-based assays like enzyme-linked immunosorbent assays (ELISAs), which are routinely used to assess cross-reactivity. Here, we have used microfluidic antibody affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high-affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory reactivation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2. !!{{ Keywords: }} SARS-CoV-2; antibody affinity; antibody concentration; antibody profiling; cross-reactivity; microfluidics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982494/ 565 2373-8227 ACS Infectious Diseases Washington, DC : ACS Publications
1126077 897 진단 the SARS-CoV-2 Virus the sars-cov-2 abstract None 24045 10.1021/acsinfecdis.1c00486 Microfluidic Antibody Affinity Profiling Reveals the Role of Memory Reactivation and Cross-Reactivity in the Defense Against SARS-CoV-2 Viola Denninger@@@Catherine K Xu@@@Georg Meisl@@@Alexey S Morgunov@@@Sebastian Fiedler@@@Alison Ilsley@@@Marc Emmenegger@@@Anisa Y Malik@@@Monika A Piziorska@@@Matthias M Schneider@@@Sean R A Devenish@@@Vasilis Kosmoliaptsis@@@Adriano Aguzzi@@@Heike Fiegler@@@Tuomas P J Knowles 202204 Article PMC {{{ Abstract }}} !! Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potentially beneficial and detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be reactivated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Determining the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be disentangled by surface-based assays like enzyme-linked immunosorbent assays (ELISAs), which are routinely used to assess cross-reactivity. Here, we have used microfluidic antibody affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high-affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory reactivation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2. !!{{ Keywords: }} SARS-CoV-2; antibody affinity; antibody concentration; antibody profiling; cross-reactivity; microfluidics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982494/ 565 2373-8227 ACS Infectious Diseases Washington, DC : ACS Publications
1126642 897 진단 measure Term measure abstract None 24077 10.1093/cid/ciaa849 Estimation of SARS-CoV-2 Infection Fatality Rate by Real-time Antibody Screening of Blood Donors Christian Erikstrup@@@Christoffer Egeberg Hother@@@Ole Birger Vestager Pedersen@@@K?re Mølbak@@@Robert Leo Skov@@@Dorte Kinggaard Holm@@@Susanne Gjørup Sækmose@@@Anna Christine Nilsson@@@Patrick Terrence Brooks@@@Jens Kjærgaard Boldsen@@@Christina Mikkelsen@@@Mikkel Gybel-Brask@@@Erik Sørensen@@@Khoa Manh Dinh@@@Susan Mikkelsen@@@Bjarne Kuno Møller@@@Thure Haunstrup@@@Lene Harritshøj@@@Bitten Aagaard Jensen@@@Henrik Hjalgrim@@@Søren Thue Lillevang@@@Henrik Ullum 202101 Article PMC {{{ Abstract }}} !!{{ Background: }} The pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has tremendous consequences for our societies. Knowledge of the seroprevalence of SARS-CoV-2 is needed to accurately monitor the spread of the epidemic and to calculate the infection fatality rate (IFR). These measures may help the authorities make informed decisions and adjust the current societal interventions. The objective was to perform nationwide real-time seroprevalence surveying among blood donors as a tool to estimate previous SARS-CoV-2 infections and the population-based IFR. !!{{ Methods: }} Danish blood donors aged 17-69 years giving blood 6 April to 3 May were tested for SARS-CoV-2 immunoglobulin M and G antibodies using a commercial lateral flow test. Antibody status was compared between geographical areas, and an estimate of the IFR was calculated. Seroprevalence was adjusted for assay sensitivity and specificity taking the uncertainties of the test validation into account when reporting the 95% confidence intervals (CIs). !!{{ Results: }} The first 20 640 blood donors were tested, and a combined adjusted seroprevalence of 1.9% (95% CI, .8-2.3) was calculated. The seroprevalence differed across areas. Using available data on fatalities and population numbers, a combined IFR in patients &lt;70 years is estimated at 89 per 100 000 (95% CI, 72-211) infections. !!{{ Conclusions: }} The IFR was estimated to be slightly lower than previously reported from other countries not using seroprevalence data. The IFR is likely severalfold lower than the current estimate. We have initiated real-time nationwide anti-SARS-CoV-2 seroprevalence surveying of blood donations as a tool in monitoring the epidemic. !!{{ Keywords: }} COVID-19; SARS-CoV-2; emerging infectious disease; epidemic monitoring; seroprevalence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337681/ 103 1058-4838 Clinical Infectious Diseases: An Official Publicat Oxford : Oxford University Press. 4.39400
1126772 897 진단 omicron Virus omicron title 오미크론 24085 10.1016/j.ccell.2022.04.012 Longitudinal COVID-19-vaccination-induced antibody responses and Omicron neutralization in patients with lung cancer Philip C Mack@@@Jorge E Gomez@@@Ananda M Rodilla@@@Juan Manuel Carre?o@@@Chih-Yuan Hsu@@@Christian Rolfo@@@Noy Meshulami@@@Amy Moore@@@Rachel I Brody@@@Jennifer C King@@@Jacquelyn Treatman@@@Sooyun Lee@@@Ariel Raskin@@@Komal Srivastava@@@Charles R Gleason@@@Diego de Miguel-Perez@@@PARIS/PSP study group@@@Johnstone Tcheou@@@Dominika Bielak@@@Rashmi Acharya@@@David E Gerber@@@Nicholas Rohs@@@Claudia I Henschke@@@David F Yankelevitz@@@Viviana Simon@@@John D Minna@@@Paul A Bunn Jr@@@Adolfo Garc?a-Sastre@@@Florian Krammer@@@Yu Shyr@@@Fred R Hirsch 202206 Article PMC None https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020481/ 928 1535-6108 Cancer cell Cambridge, Mass. : Cell Press
1214328 897 진단 inclusion criteria Term inclusion criteria abstract None 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1214329 897 진단 individual Term individual abstract None 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1104955 897 진단 Pregnancy Term pregnancy author 임신 23237 10.1016/j.celrep.2021.109959 Selective functional antibody transfer into the breastmilk after SARS-CoV-2 infection Krista M. Pullen@@@Caroline Atyeo@@@Ai-Ris Y. Collier@@@Kathryn J. Gray@@@Mandy B. Belfort@@@Douglas A. Lauffenburger@@@Andrea G. Edlow@@@Galit Alter 202110 Article PMC Summary Antibody transfer via breastmilk represents an evolutionary strategy to boost immunity in early life. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies have been observed in the breastmilk, the functional quality of these antibodies remains unclear. Here, we apply systems serology to characterize SARS-CoV-2-specific antibodies in maternal serum and breastmilk to compare the functional characteristics of antibodies in these fluids. Distinct SARS-CoV-2-specific antibody responses are observed in the serum and breastmilk of lactating individuals previously infected with SARS-CoV-2, with a more dominant transfer of immunoglobulin A (IgA) and IgM into breastmilk. Although IgGs are present in breastmilk, they are functionally attenuated. We observe preferential transfer of antibodies capable of eliciting neutrophil phagocytosis and neutralization compared to other functions, pointing to selective transfer of certain functional antibodies to breastmilk. These data highlight the preferential transfer of SARS-CoV-2-specific IgA and IgM to breastmilk, accompanied by select IgG subpopulations, positioned to create a non-pathologic but protective barrier against coronavirus disease 2019 (COVID-19). Graphical abstract Highlights ? SARS-CoV-2 induces pathogen-specific antibodies in maternal blood and breastmilk ? Breastmilk antibodies are functionally attenuated compared to serum antibodies ? Neutrophil phagocytosis and neutralization are preferentially present in breastmilk ? Disease severity, but not time since symptom onset, impacts transfer to breastmilk Pullen et?al. characterize the functionality of SARS-CoV-2-specific antibodies in maternal blood and breastmilk after SARS-CoV-2 infection. Although infection elicits polyfunctional IgG in blood, breastmilk mostly contains neutralizing and neutrophil-activating IgA, IgM, and IgG, suggesting a selection of specific, non-inflammatory antibody subsets in the breastmilk. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531199/ 872 2211-1247 Cell Reports [Cambridge, MA] : Cell Press
1104954 897 진단 positioned Action positioned abstract None 23237 10.1016/j.celrep.2021.109959 Selective functional antibody transfer into the breastmilk after SARS-CoV-2 infection Krista M. Pullen@@@Caroline Atyeo@@@Ai-Ris Y. Collier@@@Kathryn J. Gray@@@Mandy B. Belfort@@@Douglas A. Lauffenburger@@@Andrea G. Edlow@@@Galit Alter 202110 Article PMC Summary Antibody transfer via breastmilk represents an evolutionary strategy to boost immunity in early life. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies have been observed in the breastmilk, the functional quality of these antibodies remains unclear. Here, we apply systems serology to characterize SARS-CoV-2-specific antibodies in maternal serum and breastmilk to compare the functional characteristics of antibodies in these fluids. Distinct SARS-CoV-2-specific antibody responses are observed in the serum and breastmilk of lactating individuals previously infected with SARS-CoV-2, with a more dominant transfer of immunoglobulin A (IgA) and IgM into breastmilk. Although IgGs are present in breastmilk, they are functionally attenuated. We observe preferential transfer of antibodies capable of eliciting neutrophil phagocytosis and neutralization compared to other functions, pointing to selective transfer of certain functional antibodies to breastmilk. These data highlight the preferential transfer of SARS-CoV-2-specific IgA and IgM to breastmilk, accompanied by select IgG subpopulations, positioned to create a non-pathologic but protective barrier against coronavirus disease 2019 (COVID-19). Graphical abstract Highlights ? SARS-CoV-2 induces pathogen-specific antibodies in maternal blood and breastmilk ? Breastmilk antibodies are functionally attenuated compared to serum antibodies ? Neutrophil phagocytosis and neutralization are preferentially present in breastmilk ? Disease severity, but not time since symptom onset, impacts transfer to breastmilk Pullen et?al. characterize the functionality of SARS-CoV-2-specific antibodies in maternal blood and breastmilk after SARS-CoV-2 infection. Although infection elicits polyfunctional IgG in blood, breastmilk mostly contains neutralizing and neutrophil-activating IgA, IgM, and IgG, suggesting a selection of specific, non-inflammatory antibody subsets in the breastmilk. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531199/ 872 2211-1247 Cell Reports [Cambridge, MA] : Cell Press
1104953 897 진단 phagocytosis Term phagocytosis abstract 포식 23237 10.1016/j.celrep.2021.109959 Selective functional antibody transfer into the breastmilk after SARS-CoV-2 infection Krista M. Pullen@@@Caroline Atyeo@@@Ai-Ris Y. Collier@@@Kathryn J. Gray@@@Mandy B. Belfort@@@Douglas A. Lauffenburger@@@Andrea G. Edlow@@@Galit Alter 202110 Article PMC Summary Antibody transfer via breastmilk represents an evolutionary strategy to boost immunity in early life. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies have been observed in the breastmilk, the functional quality of these antibodies remains unclear. Here, we apply systems serology to characterize SARS-CoV-2-specific antibodies in maternal serum and breastmilk to compare the functional characteristics of antibodies in these fluids. Distinct SARS-CoV-2-specific antibody responses are observed in the serum and breastmilk of lactating individuals previously infected with SARS-CoV-2, with a more dominant transfer of immunoglobulin A (IgA) and IgM into breastmilk. Although IgGs are present in breastmilk, they are functionally attenuated. We observe preferential transfer of antibodies capable of eliciting neutrophil phagocytosis and neutralization compared to other functions, pointing to selective transfer of certain functional antibodies to breastmilk. These data highlight the preferential transfer of SARS-CoV-2-specific IgA and IgM to breastmilk, accompanied by select IgG subpopulations, positioned to create a non-pathologic but protective barrier against coronavirus disease 2019 (COVID-19). Graphical abstract Highlights ? SARS-CoV-2 induces pathogen-specific antibodies in maternal blood and breastmilk ? Breastmilk antibodies are functionally attenuated compared to serum antibodies ? Neutrophil phagocytosis and neutralization are preferentially present in breastmilk ? Disease severity, but not time since symptom onset, impacts transfer to breastmilk Pullen et?al. characterize the functionality of SARS-CoV-2-specific antibodies in maternal blood and breastmilk after SARS-CoV-2 infection. Although infection elicits polyfunctional IgG in blood, breastmilk mostly contains neutralizing and neutrophil-activating IgA, IgM, and IgG, suggesting a selection of specific, non-inflammatory antibody subsets in the breastmilk. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531199/ 872 2211-1247 Cell Reports [Cambridge, MA] : Cell Press
1105143 897 진단 Immune cell Cell immune cell abstract None 23236 10.1016/j.celrep.2021.108863 Metabolic programs define dysfunctional immune responses in severe COVID-19 patients Elizabeth A. Thompson@@@Katherine Cascino@@@Alvaro A. Ordonez@@@Weiqiang Zhou@@@Ajay Vaghasia@@@Anne Hamacher-Brady@@@Nathan R. Brady@@@Im-Hong Sun@@@Rulin Wang@@@Avi Z. Rosenberg@@@Michael Delannoy@@@Richard Rothman@@@Katherine Fenstermacher@@@Lauren Sauer@@@Kathyrn Shaw-Saliba@@@Evan M. Bloch@@@Andrew D. Redd@@@Aaron A.R. Tobian@@@Maureen Horton@@@Kellie Smith@@@Andrew Pekosz@@@Franco R. D’Alessio@@@Srinivasan Yegnasubramanian@@@Hongkai Ji@@@Andrea L. Cox@@@Jonathan D. Powell 202102 Article PMC Summary It is unclear why some SARS-CoV-2 patients readily resolve infection while others develop severe disease. By interrogating metabolic programs of immune cells in severe and recovered coronavirus disease 2019 (COVID-19) patients compared with other viral infections, we identify a unique population of T?cells. These T?cells express increased Voltage-Dependent Anion Channel 1 (VDAC1), accompanied by gene programs and functional characteristics linked to mitochondrial dysfunction and apoptosis. The percentage of these cells increases in elderly patients and correlates with lymphopenia. Importantly, T?cell apoptosis is inhibited in?vitro by targeting the oligomerization of VDAC1 or blocking caspase activity. We also observe an expansion of myeloid-derived suppressor cells with unique metabolic phenotypes specific to COVID-19, and their presence distinguishes severe from mild disease. Overall, the identification of these metabolic phenotypes provides insight into the dysfunctional immune response in acutely ill COVID-19 patients and provides a means to predict and track disease severity and/or design metabolic therapeutic regimens. Graphical abstract Highlights ? T cells with a unique metabolic profile are expanded in acute COVID-19 ? These T?cells are prone to mitochondrial apoptosis, correlating with lymphopenia ? Metabolically distinct myeloid-derived suppressor cells increase in acute COVID-19 ? The presence of these M-MDSCs in acute COVID-19 correlates with disease severity The precise immunological defects that correlate with disease severity in COVID-19 have yet to be determined. Based on immune-metabolic profiling, Thompson et?al. identify unique populations of T?cells and myeloid cells that correlate with disease severity. These findings highlight metabolic pathways as possible therapeutic targets for COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908880/ 872 2211-1247 Cell Reports [Cambridge, MA] : Cell Press
1108418 897 진단 Disease prevalence Term disease prevalence abstract 질병 유병률 23349 10.1016/j.jim.2022.113243 Clinical and analytical evaluation of the Abbott AdviseDx quantitative SARS-CoV-2 IgG assay and comparison with two other serological tests Gabriel N Maine@@@Subhashree Mallika Krishnan@@@Kelly Walewski@@@Jillian Trueman@@@Elizabeth Sykes@@@Qian Sun 202204 Article PMC {{{ Abstract }}} !!{{ Introduction: }} Serological testing is an important tool to assist with assessing the immune response to SARS-CoV-2 infections, the causative agent of COVID-19. A quantitative assay was recently developed by Abbott Laboratories to measures antibodies against the receptor binding domain of the spike protein. In addition to assessing disease prevalence, this assay is useful towards determining the scale and duration of the humoral response to infection and vaccination. Here we evaluated the clinical and analytical performance of the quantitative Abbott AdviseDx SARS-CoV-2 IgG II assay and characterized the longitudinal dynamics of the IgG response against SARS-CoV-2 in 402 infected individuals up to 322 days post-symptom onset. !!{{ Methods: }} To assess test sensitivity, 1257 serum specimens derived from 402 patients positive for SARS-CoV-2 by RT-PCR were analyzed on the Abbott Alinity platform. To evaluate test specificity, 394 specimens were tested from patients who were symptomatic but PCR negative for SARS-CoV-2, as well as 305 archived pre-pandemic samples. To further characterize test performance metrics, we evaluated assay precision and linearity. !!{{ Results: }} The Abbott AdviseDx SARS-CoV-2 IgG II assay exhibited diagnostic specificity of 99.02% using 305 pre - COVID-19 serum specimens and 98.73% using 394 PCR negative specimens. Using 1257 sequential serum samples collected from PCR-confirmed individuals, clinical test sensitivity of the assay was 39.7% at 3-7 days, 75.9% at 8-14 days, 95.6% at 15-21 days, and 98.7% at 4-5 weeks post-symptom onset. The assay is linear across the analytical measurement range claimed by the manufacturer (22-25,000 AU/mL) and exhibited good analytical precision. The median concentration of IgG increased steadily from &lt;22 AU/mL at 3-7 days post-symptom onset, to a peak of 14,421 AU/mL at 6-7 weeks. Although antibody concentration started to decline at 8-9 weeks following symptom onset, all patients remained seropositive during the observation period. When the positivity rate of this assay was compared with the Abbott anti-NP IgG and EUROIMMUN anti-S1 IgG tests, clinical sensitivity of the Abbott AdviseDx SARS-CoV-2 IgG II assay was the highest at all time points with the exception of 4-5 weeks after symptom onset. !!{{ Conclusion: }} The Abbott AdviseDx SARS-CoV-2 IgG II assay offers high test specificity and sensitivity across a broad reportable range. We anticipate this assay will be a useful towards quantitatively assessing the humoral immune response to COVID-19 infection and vaccination. !!{{ Keywords: }} Abbott; Anti-RBD; Anti-spike; Coronavirus; SARS-CoV-2 IgG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847080/ 718 0022-1759 Journal of Immunological Methods Amsterdam : Elsevier.
1114991 897 진단 SARS-CoV-2 Virus sars-cov-2 abstract 제2형 중증급성호흡기증후군 코로나바이러스 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114992 897 진단 Science Term science abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114993 897 진단 second dose Term second dose abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114994 897 진단 Serious Adverse Event Term serious adverse event abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114995 897 진단 seropositive Term seropositive abstract 혈청검사양성 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1214330 897 진단 individuals Patient individual abstract None 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1104952 897 진단 pathogen-specific Term pathogen-specific abstract None 23237 10.1016/j.celrep.2021.109959 Selective functional antibody transfer into the breastmilk after SARS-CoV-2 infection Krista M. Pullen@@@Caroline Atyeo@@@Ai-Ris Y. Collier@@@Kathryn J. Gray@@@Mandy B. Belfort@@@Douglas A. Lauffenburger@@@Andrea G. Edlow@@@Galit Alter 202110 Article PMC Summary Antibody transfer via breastmilk represents an evolutionary strategy to boost immunity in early life. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies have been observed in the breastmilk, the functional quality of these antibodies remains unclear. Here, we apply systems serology to characterize SARS-CoV-2-specific antibodies in maternal serum and breastmilk to compare the functional characteristics of antibodies in these fluids. Distinct SARS-CoV-2-specific antibody responses are observed in the serum and breastmilk of lactating individuals previously infected with SARS-CoV-2, with a more dominant transfer of immunoglobulin A (IgA) and IgM into breastmilk. Although IgGs are present in breastmilk, they are functionally attenuated. We observe preferential transfer of antibodies capable of eliciting neutrophil phagocytosis and neutralization compared to other functions, pointing to selective transfer of certain functional antibodies to breastmilk. These data highlight the preferential transfer of SARS-CoV-2-specific IgA and IgM to breastmilk, accompanied by select IgG subpopulations, positioned to create a non-pathologic but protective barrier against coronavirus disease 2019 (COVID-19). Graphical abstract Highlights ? SARS-CoV-2 induces pathogen-specific antibodies in maternal blood and breastmilk ? Breastmilk antibodies are functionally attenuated compared to serum antibodies ? Neutrophil phagocytosis and neutralization are preferentially present in breastmilk ? Disease severity, but not time since symptom onset, impacts transfer to breastmilk Pullen et?al. characterize the functionality of SARS-CoV-2-specific antibodies in maternal blood and breastmilk after SARS-CoV-2 infection. Although infection elicits polyfunctional IgG in blood, breastmilk mostly contains neutralizing and neutrophil-activating IgA, IgM, and IgG, suggesting a selection of specific, non-inflammatory antibody subsets in the breastmilk. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531199/ 872 2211-1247 Cell Reports [Cambridge, MA] : Cell Press
1115017 897 진단 Border Term border title 경계 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1114996 897 진단 severity Term severity abstract 중증도 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114997 897 진단 significantly increased Action significantly increased abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114998 897 진단 technology Term technology abstract 기술 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1114999 897 진단 threshold Term threshold abstract 문턱값 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1115000 897 진단 translation Action translation abstract 번역 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1115001 897 진단 Trial Term trial abstract 시험 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1115002 897 진단 vaccination Term vaccination abstract 백신 접종 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1115003 897 진단 vaccination against COVID-19 Term vaccination against COVID-19 abstract abnormality 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1108949 897 진단 positive Action positive abstract None 23373 10.1093/cid/ciab519 Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in All of Us Research Program Participants, 2 January to 18 March 2020 Keri N Althoff@@@David J Schlueter@@@Hoda Anton-Culver@@@James Cherry@@@Joshua C Denny@@@Isaac Thomsen@@@Elizabeth W Karlson@@@Fiona P Havers@@@Mine S Cicek@@@Stephen N Thibodeau@@@Ligia A Pinto@@@Douglas Lowy@@@Bradley A Malin@@@Lucila Ohno-Machado@@@Carolyn Williams@@@David Goldstein@@@Aymone Kouame@@@Andrea Ramirez@@@Adrienne Roman@@@Norman E Sharpless@@@Kelly A Gebo@@@Sheri D Schully 202203 Article PMC {{{ Abstract }}} !!{{ Background: }} With limited severe acute respiratory syndrome coronavirus (SARS-CoV-2) testing capacity in the United States at the start of the epidemic (January-March 2020), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic. !!{{ Methods: }} All of Us study participants in all 50 US states provided blood specimens during study visits from 2 January to 18 March 2020. Participants were considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies with the Abbott Architect SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. The sensitivity and specificity of these ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated, along with 95% confidence intervals (CIs). !!{{ Results: }} The estimated sensitivities of the Abbott and EUROIMMUN assays were 100% (107 of 107 [95% CI: 96.6%-100%]) and 90.7% (97 of 107 [83.5%-95.4%]), respectively, and the estimated specificities were 99.5% (995 of 1000 [98.8%-99.8%]) and 99.7% (997 of 1000 [99.1%-99.9%]), respectively. The net sensitivity and specificity of our sequential testing algorithm were 90.7% (97 of 107 [95% CI: 83.5%-95.4%]) and 100.0% (1000 of 1000 [99.6%-100%]), respectively. Of the 24 079 study participants with blood specimens from 2 January to 18 March 2020, 9 were seropositive, 7 before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. !!{{ Conclusions: }} Our findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states. !!{{ Keywords: }} All of Us Research Program; Epidemic; Immunoglobulin G antibodies; SARS-CoV-2; United States. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384413/ 103 1058-4838 Clinical Infectious Diseases: An Official Publicat Oxford : Oxford University Press. 4.39400
1115004 897 진단 vaccination schedule Term vaccination schedule abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1115005 897 진단 Vaccine Drug vaccine abstract 백신 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1115006 897 진단 virus strain Term virus strain abstract None 23591 10.1016/S1473-3099(21)00681-2 Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Gang Zeng@@@Qianhui Wu@@@Hongxing Pan@@@Minjie Li@@@Juan Yang@@@Lin Wang@@@Zhiwei Wu@@@Deyu Jiang@@@Xiaowei Deng@@@Kai Chu@@@Wen Zheng@@@Lei Wang@@@Wanying Lu@@@Bihua Han@@@Yuliang Zhao@@@Fengcai Zhu@@@Hongjie Yu@@@Weidong Yin 202204 Clinical Trial PMC {{{ Abstract }}} !!{{ Background: }} Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. !!{{ Methods: }} In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574 . !!{{ Findings: }} 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. !!{{ Interpretation: }} A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. !!{{ Funding: }} National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. !!{{ Translation: }} For the Mandarin translation of the abstract see Supplementary Materials section. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651254/ 36 1473-3099 The Lancet. Infectious Diseases New York, NY : Elsevier Science ; The Lancet Pub. Group 10.23600
1115007 897 진단 95% CI Term 95% CI abstract None 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115008 897 진단 absolute reduction Term absolute reduction abstract None 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115987 897 진단 were assessed Action were assessed abstract None 23613 10.1001/jamanetworkopen.2022.11497 Factors Associated With Serological Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Rituximab Andreas Tolf@@@Anna Wiberg@@@Malin M?ller@@@Faisal Hayat Nazir@@@Ivan Pavlovic@@@Ida Laur?n@@@Sara Mangsbo@@@Joachim Burman 202205 Article PMC {{{ Abstract }}} !!{{ Importance: }} B-cell-depleting monoclonal antibodies are widely used for treatment of multiple sclerosis but are associated with an impaired response to vaccines. !!{{ Objective: }} To identify factors associated with a favorable vaccine response to tozinameran. !!{{ Design, setting, and participants: }} This prospective cohort study was conducted in a specialized multiple sclerosis clinic at a university hospital from January 21 to December 1, 2021. Of 75 patients evaluated for participation who received a diagnosis of multiple sclerosis with planned or ongoing treatment with rituximab, 69 were included in the study, and data from 67 were analyzed. !!{{ Exposures: }} Sex, age, number of previous rituximab infusions, accumulated dose of rituximab, previous COVID-19 infection, time since last rituximab treatment, CD19+ B-cell count before vaccination, CD4+ T-cell count, and CD8+ T-cell count were considered potential factors associated with the main outcome. !!{{ Main outcomes and measures: }} Serological vaccine responses were measured by quantitation of anti-spike immunoglobulin G (IgG) antibodies, anti-receptor-binding domain (RBD) IgG antibodies, and their neutralizing capacities. Cellular responses to spike protein-derived SARS-CoV-2 peptide pools were assessed by counting interferon gamma spot-forming units in a FluoroSpot assay. !!{{ Results: }} Among 60 patients with ongoing rituximab treatment (49 women [82%]; mean (SD) age, 43 [10] years), the median (range) disease duration was 9 (1-29) years, and the median (range) dose of rituximab was 2750 (500-10 000) mg during a median (range) time of 2.8 (0.5-8.3) years. The median (range) follow-up from the first vaccination dose was 7.3 (4.3-10.0) months. Vaccine responses were determined before vaccination with tozinameran and 6 weeks after vaccination. By using established cutoff values for anti-spike IgG (264 binding antibody units/mL) and anti-RBD IgG (506 binding antibody units/mL), the proportion of patients with a positive response increased with the number of B cells, which was the only factor associated with these outcomes. A cutoff for the B-cell count of at least 40/μL was associated with an optimal serological response. At this cutoff, 26 of 29 patients (90%) had positive test results for anti-spike IgG and 21 of 29 patients (72%) for anti-RBD IgG, and 27 of 29 patients (93%) developed antibodies with greater than 90% inhibition of angiotensin-converting enzyme 2. No factor associated with the cellular response was identified. Depending on the peptide pool, 21 of 25 patients (84%) to 22 of 25 patients (88%) developed a T-cell response with interferon gamma production at the B-cell count cutoff of at least 40/μL. !!{{ Conclusions and relevance: }} This cohort study found that for an optimal vaccine response from tozinameran, rituximab-treated patients with multiple sclerosis may be vaccinated as soon as possible, with rituximab treatment delayed until B-cell counts have reached at least 40/μL. An additional vaccination with tozinameran should be considered at that point. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096596/ 71 2574-3805 JAMA Network Open Chicago, IL : American Medical Association
1115014 897 진단 bamlanivimab Drug bamlanivimab title,abstract Bamlanivimab 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115015 897 진단 BMI Term bmi abstract BMI 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115020 897 진단 chi-square test Term chi-square test abstract None 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115021 897 진단 Chronic kidney disease Disease chronic kidney disease abstract 만성 신부전 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115022 897 진단 Comorbidities Term comorbidity abstract 동반 질환 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115027 897 진단 coronavirus disease Disease coronavirus disease abstract 코로나바이러스 질환 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1126513 897 진단 conducted Action conducted abstract None 24074 10.1016/j.cmi.2021.09.036 Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review Simon Galmiche@@@Liem Binh Luong Nguyen@@@Eric Tartour@@@Xavier de Lamballerie@@@Linda Wittkop@@@Paul Loubet@@@Odile Launay 202202 Review PMC {{{ Abstract }}} !!{{ Background: }} Available data show that COVID-19 vaccines may be less effective in immunocompromised populations, who are at increased risk of severe COVID-19. !!{{ Objectives: }} We conducted a systematic review of literature to assess immunogenicity, efficacy and effectiveness of COVID-19 vaccines in immunocompromised populations. !!{{ Data sources: }} We searched Medline and Embase databases. !!{{ Study eligibility criteria, patients, interventions: }} We included studies of COVID-19 vaccines after complete vaccination in immunocompromised patients until 31 August 2021. Studies with &lt;10 patients, safety data only and case series of breakthrough infections were excluded. !!{{ Methods: }} Risk of bias was assessed via the tool developed by the National Institutes of Health on interventional and observational studies. Immunogenicity was assessed through non-response rate defined as no anti-SARS-CoV-2 spike protein antibodies, efficacy and effectiveness by the relative reduction in risk of SARS-CoV-2 infection or COVID-19. We collected factors associated with the risk of non-response. We presented collected data by immunosuppression type. !!{{ Results: }} We screened 5917 results, included 162 studies. There were 157 on immunogenicity in 25 209 participants, including 7835 cancer or haematological malignancy patients (31.1%), 6302 patients on dialysis (25.0%), 5974 solid organ transplant recipients (23.7%) and 4680 immune-mediated disease patients (18.6%). Proportion of non-responders seemed higher among solid organ transplant recipients (range 18-100%) and patients with haematological malignancy (range 14-61%), and lower in patients with cancer (range 2-36%) and patients on dialysis (range 2-30%). Risk factors for non-response included older age, use of corticosteroids, immunosuppressive or anti-CD20 agent. Ten studies evaluated immunogenicity of an additional dose. Five studies evaluated vaccine efficacy or effectiveness: three on SARS-CoV-2 infection (range 71-81%), one on COVID-19-related hospitalization (62.9%), one had a too small sample size. !!{{ Conclusions: }} This systematic review highlights the risk of low immunogenicity of COVID-19 vaccines in immunocompromised populations, especially solid organ transplant recipients and patients with haematological malignancy. Despite lack of vaccine effectiveness data, enhanced vaccine regimens may be necessary. !!{{ Keywords: }} COVID-19; Cancer; Dialysis; Effectiveness; Efficacy; Immunogenicity; SARS-CoV-2 immunocompromised; Solid organ transplant; Vaccine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595936/ 884 1198-743X Clinical microbiology and infection : the official London : Elsevier. 3.11100
1115028 897 진단 COVID-19 Disease covid-19 title,abstract 코로나-19 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115029 897 진단 COVID-19 patient Term covid-19 patient abstract None 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115030 897 진단 criteria Term criteria abstract 기준 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115031 897 진단 death Term death abstract 사망 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1115032 897 진단 demographics Term demographic abstract None 23592 10.5811/westjem.2021.10.52668 Bamlanivimab Reduces ED Returns and Hospitalizations and May Reduce COVID-19 Burden on Low-resource Border Hospitals Faith C Quenzer@@@Andrew T Lafree@@@Londyn Grey@@@Sukhdeep Singh@@@Cameron Smyers@@@Bruce Balog@@@Henry Montilla Guedez@@@Kaitlin McIntyre@@@Sharon Wulfovich@@@Juli Ramirez@@@Talia Saikhon@@@Christian Tomaszewski 202203 Article PMC {{{ Abstract }}} !!{{ Introduction: }} To evaluate the effectiveness of bamlanivimab at reducing return emergency department (ED) visits in primarily Latinx/Hispanic patients with mild or moderate coronavirus disease 2019 (COVID-19). Secondary aims were to evaluate the prevention of subsequent hospitalizations and deaths in a resource-limited United States (U.S.)-Mexico border hospital. !!{{ Methods: }} We conducted a retrospective, open-label interventional study on 270 eligible adult patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met criteria for receiving bamlanivimab from November 1, 2020 to January 31, 2021. The main outcomes of 14-day return visits to the ED and hospitalizations due to COVID-19 were compared between two groups - those who received bamlanivimab (exposed group) and those who did not receive bamlanivimab (unexposed group). Outcomes were analyzed through chi-square tests followed by multivariate regression modeling to adjust for patient demographics, characteristics, and comorbidities. !!{{ Results: }} There were 136 COVID-19 patients who received bamlanivimab in the ED prior to discharge and an unexposed group of 134 COVID-19 patients who were evaluated and discharged from the ED without receiving bamlanivimab. Overall, mean age was 61.7 (S.D. +/-13.9) years, mean body mass index (BMI) 31.0 (S.D. +/-6.6) kg/m 2 , 91.5% identified as Latinx/Hispanic, 51.9% male, and 80.7% reported at least one comorbidity. Most commonly reported comorbidities were obesity (22.6%), hypertension (59.6%), and diabetes (41.1%). The bamlanivimab group had a 22.8% (mean estimate = 0.7717, 95% CI [0.6482, 0.8611]) risk reduction or 84.4% (0.3030, 95% CI = 0.166, 0.554, p=.0001) absolute reduction of ED return visits within 14 days compared to controls after adjusting for chronic kidney disease. The bamlanivimab group had 19.0% (mean estimate=0.8097, 95% CI [0.6451, 0.9087]) risk reduction or 96.2% (0.235, 95% CI 0.100, 0.550, p=0.0008) absolute reduction of subsequent hospitalizations compared to unexposed patients after adjusting for diabetes status. !!{{ Conclusion: }} Bamlanivimab infusions for high-risk COVID-19 patients in the ED substantially reduced the risk of return visits to the ED and hospitalizations in our primarily Latinx/Hispanic population. Monoclonal antibody infusions may help reduce hospital utilization during COVID-19 surges at U.S.-Mexico border hospitals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183783/ 598 1936-900X Western Journal of Emergency Medicine Irvine, CA : Department of Emergency Medicine, University of California, Irvine.
1214331 897 진단 infected individual Patient infected individual abstract None 3548 10.1186/s13063-021-05241-5 A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial 202106 Letter PMC Objectives It is currently thought that most?but not all?individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. Trial design The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. Participants The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. Inclusion criteria: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet’s User Manual; self-reported) Staff involved in the management or conduct of this study Intervention and comparator All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app’s underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Main outcomes The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called “COVID-positive” mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. Randomisation All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. Blinding (masking) In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. Numbers to be randomised (sample size) 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. Trial Status Protocol version: 1.2, dated January 22 nd , 2021 Start of recruitment: February 22 nd , 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 Trial registration The trial has been registered at the Netherlands Trial Register on the 18 th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05241-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218271/ 54 1745-6215 Trials [London] : BioMed Central
1123061 897 진단 Coagulation Term coagulation title 응고물 23896 10.1111/jth.15275 Antibody-mediated platelet activation in COVID-19: A coincidence or a new mechanism of the dysregulated coagulation system? Karina Althaus@@@Jan Zlamal@@@Tamam Bakchoul 202105 Comment PMC None https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250340/ 344 1538-7933 Journal of thrombosis and haemostasis : JTH Oxford : Blackwell Pub.
1114214 897 진단 asked Action asked abstract None 23573 10.1186/s12889-022-13464-7 Seroprevalence of SARS-CoV-2 antibody among urban Iranian population: findings from the second large population-based cross-sectional study Mohammad Zamani@@@Hossein Poustchi@@@Zahra Mohammadi@@@Sahar Dalvand@@@Maryam Sharafkhah@@@Seyed Abbas Motevalian@@@Saeid Eslami@@@Amir Emami@@@Mohammad Hossein Somi@@@Jamshid Yazdani-Charati@@@Nader Saki@@@Manoochehr Karami@@@Farid Najafi@@@Iraj Mohebbi@@@Nasrollah Veisi@@@Ahmad Hormati@@@Farhad Pourfarzi@@@Reza Ghadimi@@@Alireza Ansari-Moghaddam@@@Hamid Sharifi@@@Gholamreza Roshandel@@@Fariborz Mansour-Ghanaei@@@Farahnaz Joukar@@@Amaneh Shayanrad@@@Sareh Eghtesad@@@Ahmadreza Niavarani@@@Alireza Delavari@@@Soudeh Kaveh@@@Akbar Feizesani@@@Melineh Markarian@@@Fatemeh Shafighian@@@Alireza Sadjadi@@@Maryam Darvishian@@@Reza Malekzadeh 202205 Article PMC {{{ Abstract }}} !!{{ Background: }} The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. !!{{ Methods: }} This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. !!{{ Results: }} The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. !!{{ Conclusions: }} Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021. !!{{ Keywords: }} COVID-19; General population; Infection; SARS-CoV-2; Seroprevalence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125542/ 28 2474-7629 BMC Public Health London : BioMed Central
1114250 897 진단 seropositive individual Term seropositive individual abstract None 23573 10.1186/s12889-022-13464-7 Seroprevalence of SARS-CoV-2 antibody among urban Iranian population: findings from the second large population-based cross-sectional study Mohammad Zamani@@@Hossein Poustchi@@@Zahra Mohammadi@@@Sahar Dalvand@@@Maryam Sharafkhah@@@Seyed Abbas Motevalian@@@Saeid Eslami@@@Amir Emami@@@Mohammad Hossein Somi@@@Jamshid Yazdani-Charati@@@Nader Saki@@@Manoochehr Karami@@@Farid Najafi@@@Iraj Mohebbi@@@Nasrollah Veisi@@@Ahmad Hormati@@@Farhad Pourfarzi@@@Reza Ghadimi@@@Alireza Ansari-Moghaddam@@@Hamid Sharifi@@@Gholamreza Roshandel@@@Fariborz Mansour-Ghanaei@@@Farahnaz Joukar@@@Amaneh Shayanrad@@@Sareh Eghtesad@@@Ahmadreza Niavarani@@@Alireza Delavari@@@Soudeh Kaveh@@@Akbar Feizesani@@@Melineh Markarian@@@Fatemeh Shafighian@@@Alireza Sadjadi@@@Maryam Darvishian@@@Reza Malekzadeh 202205 Article PMC {{{ Abstract }}} !!{{ Background: }} The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. !!{{ Methods: }} This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. !!{{ Results: }} The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. !!{{ Conclusions: }} Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021. !!{{ Keywords: }} COVID-19; General population; Infection; SARS-CoV-2; Seroprevalence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125542/ 28 2474-7629 BMC Public Health London : BioMed Central
1114251 897 진단 seroprevalence. Term seroprevalence author None 23573 10.1186/s12889-022-13464-7 Seroprevalence of SARS-CoV-2 antibody among urban Iranian population: findings from the second large population-based cross-sectional study Mohammad Zamani@@@Hossein Poustchi@@@Zahra Mohammadi@@@Sahar Dalvand@@@Maryam Sharafkhah@@@Seyed Abbas Motevalian@@@Saeid Eslami@@@Amir Emami@@@Mohammad Hossein Somi@@@Jamshid Yazdani-Charati@@@Nader Saki@@@Manoochehr Karami@@@Farid Najafi@@@Iraj Mohebbi@@@Nasrollah Veisi@@@Ahmad Hormati@@@Farhad Pourfarzi@@@Reza Ghadimi@@@Alireza Ansari-Moghaddam@@@Hamid Sharifi@@@Gholamreza Roshandel@@@Fariborz Mansour-Ghanaei@@@Farahnaz Joukar@@@Amaneh Shayanrad@@@Sareh Eghtesad@@@Ahmadreza Niavarani@@@Alireza Delavari@@@Soudeh Kaveh@@@Akbar Feizesani@@@Melineh Markarian@@@Fatemeh Shafighian@@@Alireza Sadjadi@@@Maryam Darvishian@@@Reza Malekzadeh 202205 Article PMC {{{ Abstract }}} !!{{ Background: }} The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. !!{{ Methods: }} This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. !!{{ Results: }} The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. !!{{ Conclusions: }} Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021. !!{{ Keywords: }} COVID-19; General population; Infection; SARS-CoV-2; Seroprevalence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125542/ 28 2474-7629 BMC Public Health London : BioMed Central
1114252 897 진단 Seroprevalence Term seroprevalence title,abstract 혈청 유병률 23573 10.1186/s12889-022-13464-7 Seroprevalence of SARS-CoV-2 antibody among urban Iranian population: findings from the second large population-based cross-sectional study Mohammad Zamani@@@Hossein Poustchi@@@Zahra Mohammadi@@@Sahar Dalvand@@@Maryam Sharafkhah@@@Seyed Abbas Motevalian@@@Saeid Eslami@@@Amir Emami@@@Mohammad Hossein Somi@@@Jamshid Yazdani-Charati@@@Nader Saki@@@Manoochehr Karami@@@Farid Najafi@@@Iraj Mohebbi@@@Nasrollah Veisi@@@Ahmad Hormati@@@Farhad Pourfarzi@@@Reza Ghadimi@@@Alireza Ansari-Moghaddam@@@Hamid Sharifi@@@Gholamreza Roshandel@@@Fariborz Mansour-Ghanaei@@@Farahnaz Joukar@@@Amaneh Shayanrad@@@Sareh Eghtesad@@@Ahmadreza Niavarani@@@Alireza Delavari@@@Soudeh Kaveh@@@Akbar Feizesani@@@Melineh Markarian@@@Fatemeh Shafighian@@@Alireza Sadjadi@@@Maryam Darvishian@@@Reza Malekzadeh 202205 Article PMC {{{ Abstract }}} !!{{ Background: }} The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. !!{{ Methods: }} This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. !!{{ Results: }} The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. !!{{ Conclusions: }} Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021. !!{{ Keywords: }} COVID-19; General population; Infection; SARS-CoV-2; Seroprevalence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125542/ 28 2474-7629 BMC Public Health London : BioMed Central
1114253 897 진단 Serosurvey Term serosurvey abstract 세로 비 23573 10.1186/s12889-022-13464-7 Seroprevalence of SARS-CoV-2 antibody among urban Iranian population: findings from the second large population-based cross-sectional study Mohammad Zamani@@@Hossein Poustchi@@@Zahra Mohammadi@@@Sahar Dalvand@@@Maryam Sharafkhah@@@Seyed Abbas Motevalian@@@Saeid Eslami@@@Amir Emami@@@Mohammad Hossein Somi@@@Jamshid Yazdani-Charati@@@Nader Saki@@@Manoochehr Karami@@@Farid Najafi@@@Iraj Mohebbi@@@Nasrollah Veisi@@@Ahmad Hormati@@@Farhad Pourfarzi@@@Reza Ghadimi@@@Alireza Ansari-Moghaddam@@@Hamid Sharifi@@@Gholamreza Roshandel@@@Fariborz Mansour-Ghanaei@@@Farahnaz Joukar@@@Amaneh Shayanrad@@@Sareh Eghtesad@@@Ahmadreza Niavarani@@@Alireza Delavari@@@Soudeh Kaveh@@@Akbar Feizesani@@@Melineh Markarian@@@Fatemeh Shafighian@@@Alireza Sadjadi@@@Maryam Darvishian@@@Reza Malekzadeh 202205 Article PMC {{{ Abstract }}} !!{{ Background: }} The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. !!{{ Methods: }} This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. !!{{ Results: }} The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. !!{{ Conclusions: }} Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021. !!{{ Keywords: }} COVID-19; General population; Infection; SARS-CoV-2; Seroprevalence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125542/ 28 2474-7629 BMC Public Health London : BioMed Central
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