| 데이터등록일 | 데이터 수정일 | 데이터 이용기한 | 판매제공처 |
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| 2023-07-06 | 2023-07-06 | 무기한 | 비네아 |
| 데이터 제공포맷 | 데이터 제공방식 | 데이터 파일용량 | 데이터 상품구분 |
| json/zip | 다운로드 | 358.00 KB | dataset |
● 데이터 상품명 치료법 데이터셋 ● 데이터 상품 부제 COVID-19의 임상 관련 치료법 데이터셋 ● 데이터 상품 요약 인용지수 상위 의학저널에 게재된 COVID-19의 치료법에 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
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카테고리ID
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카테고리명
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키워드명
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키워드속성
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대체키워드명
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키워드출처
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키워드대역어
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논문DOI명
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논문제목
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논문저자
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논문발행연월
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논문유형
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논문출처
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논문초록
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논문URL
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저널ISSN명
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| 30471 | 901 | 치료법 | SARS-CoV-2 IgG | Term | sars-cov-2 igg | abstract | None | 8848 | 10.1128/Spectrum.00733-21 | Serological Assays for Assessing Postvaccination SARS-CoV-2 Antibody Response | Sally A. Mahmoud@@@Subhashini Ganesan@@@Shivaraj Naik@@@Safaa Bissar@@@Isra Al Zamel@@@KN Warren@@@Walid A. Zaher@@@Gulfaraz Khan | 202109 | Research Article | PMC | ABSTRACT Serological assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have crucial applications in the control and surveillance of the current COVID-19 pandemic. A large number of such assays have been developed and are now commercially available. However, there are limited studies evaluating the performance of these tests. We evaluated the performances of the following six commercially available serological assays for detecting SARS-CoV-2 antibodies: (i) Genscript cPass surrogate virus neutralization test (Genscript cPass), (ii) Diasorin-SARS-CoV-2 S1/S2 IgG detection (Diasorin-S1/S2 IgG), (iii) Alinity SARS-CoV-2 IgG II (Alinity IgG II), (iv) Diasorin-SARS-CoV-2 TrimericS IgG (Diasorin-TrimericS IgG), (v) Roche Elecsys anti-SARS-CoV-2-cobas (Roche Elecsys), and (vi) AESKU enzyme linked immunosorbent assay (AESKULISA). The results of these tests were compared against the gold standard plaque reduction neutralization test (PRNT). Roche Elecsys had the highest sensitivity, and the Genscript cPass had the highest specificity. Diasorin-TrimericS IgG had the best overall performance with the highest agreement with the PRNT results. Parallel testing of Genscript cPass with Diasorin-TrimericS IgG and Diasorin-S1/S2 IgG had the optimum performance. Based on the receiver operating characteristic (ROC) curve, lowering the cutoff from 30% to 20% in the Genscript cPass significantly increased the sensitivity and the overall agreement with the PRNT results. Commercially available serological assays are good alternatives to the standard PRNT. However, further studies on larger sample numbers are required for optimization of the assay cutoff values and for evaluation of cost effectiveness. IMPORTANCE Commercial serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available. This study adds new knowledge regarding the optimization of these assays for evaluating postvaccination antibodies status. It highlights the positive and negative aspects of each assay in terms of sensitivity, specificity, and positive and negative predictive values, compared to the gold standard neutralization test. When using serological assays to assess postvaccine immune status, a balance of all parameters needs to be considered and not simply the high specificity. This balance is particularly relevant in the current situation where countries are aiming to mass vaccinate their populations and bring this pandemic under control. Assays with good sensitivity will have a lower percentage of false negatives and thus provide confidence for vaccination. Understanding the strengths and limitations of commercially available serological assays is important, not only for better application of these tests but also to understand the immune response and the duration of protection postvaccination. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557923/ | 180 | 2165-0497 | Microbiology Spectrum | Washington, DC : ASM Press | |
| 16787 | 901 | 치료법 | positive | Action | positive | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 30472 | 901 | 치료법 | sensitivity | Term | sensitivity | abstract | 민감도 | 8848 | 10.1128/Spectrum.00733-21 | Serological Assays for Assessing Postvaccination SARS-CoV-2 Antibody Response | Sally A. Mahmoud@@@Subhashini Ganesan@@@Shivaraj Naik@@@Safaa Bissar@@@Isra Al Zamel@@@KN Warren@@@Walid A. Zaher@@@Gulfaraz Khan | 202109 | Research Article | PMC | ABSTRACT Serological assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have crucial applications in the control and surveillance of the current COVID-19 pandemic. A large number of such assays have been developed and are now commercially available. However, there are limited studies evaluating the performance of these tests. We evaluated the performances of the following six commercially available serological assays for detecting SARS-CoV-2 antibodies: (i) Genscript cPass surrogate virus neutralization test (Genscript cPass), (ii) Diasorin-SARS-CoV-2 S1/S2 IgG detection (Diasorin-S1/S2 IgG), (iii) Alinity SARS-CoV-2 IgG II (Alinity IgG II), (iv) Diasorin-SARS-CoV-2 TrimericS IgG (Diasorin-TrimericS IgG), (v) Roche Elecsys anti-SARS-CoV-2-cobas (Roche Elecsys), and (vi) AESKU enzyme linked immunosorbent assay (AESKULISA). The results of these tests were compared against the gold standard plaque reduction neutralization test (PRNT). Roche Elecsys had the highest sensitivity, and the Genscript cPass had the highest specificity. Diasorin-TrimericS IgG had the best overall performance with the highest agreement with the PRNT results. Parallel testing of Genscript cPass with Diasorin-TrimericS IgG and Diasorin-S1/S2 IgG had the optimum performance. Based on the receiver operating characteristic (ROC) curve, lowering the cutoff from 30% to 20% in the Genscript cPass significantly increased the sensitivity and the overall agreement with the PRNT results. Commercially available serological assays are good alternatives to the standard PRNT. However, further studies on larger sample numbers are required for optimization of the assay cutoff values and for evaluation of cost effectiveness. IMPORTANCE Commercial serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available. This study adds new knowledge regarding the optimization of these assays for evaluating postvaccination antibodies status. It highlights the positive and negative aspects of each assay in terms of sensitivity, specificity, and positive and negative predictive values, compared to the gold standard neutralization test. When using serological assays to assess postvaccine immune status, a balance of all parameters needs to be considered and not simply the high specificity. This balance is particularly relevant in the current situation where countries are aiming to mass vaccinate their populations and bring this pandemic under control. Assays with good sensitivity will have a lower percentage of false negatives and thus provide confidence for vaccination. Understanding the strengths and limitations of commercially available serological assays is important, not only for better application of these tests but also to understand the immune response and the duration of protection postvaccination. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557923/ | 180 | 2165-0497 | Microbiology Spectrum | Washington, DC : ASM Press | |
| 30473 | 901 | 치료법 | Serological assay | Term | serological assay | abstract | 혈청 학적 분석 | 8848 | 10.1128/Spectrum.00733-21 | Serological Assays for Assessing Postvaccination SARS-CoV-2 Antibody Response | Sally A. Mahmoud@@@Subhashini Ganesan@@@Shivaraj Naik@@@Safaa Bissar@@@Isra Al Zamel@@@KN Warren@@@Walid A. Zaher@@@Gulfaraz Khan | 202109 | Research Article | PMC | ABSTRACT Serological assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have crucial applications in the control and surveillance of the current COVID-19 pandemic. A large number of such assays have been developed and are now commercially available. However, there are limited studies evaluating the performance of these tests. We evaluated the performances of the following six commercially available serological assays for detecting SARS-CoV-2 antibodies: (i) Genscript cPass surrogate virus neutralization test (Genscript cPass), (ii) Diasorin-SARS-CoV-2 S1/S2 IgG detection (Diasorin-S1/S2 IgG), (iii) Alinity SARS-CoV-2 IgG II (Alinity IgG II), (iv) Diasorin-SARS-CoV-2 TrimericS IgG (Diasorin-TrimericS IgG), (v) Roche Elecsys anti-SARS-CoV-2-cobas (Roche Elecsys), and (vi) AESKU enzyme linked immunosorbent assay (AESKULISA). The results of these tests were compared against the gold standard plaque reduction neutralization test (PRNT). Roche Elecsys had the highest sensitivity, and the Genscript cPass had the highest specificity. Diasorin-TrimericS IgG had the best overall performance with the highest agreement with the PRNT results. Parallel testing of Genscript cPass with Diasorin-TrimericS IgG and Diasorin-S1/S2 IgG had the optimum performance. Based on the receiver operating characteristic (ROC) curve, lowering the cutoff from 30% to 20% in the Genscript cPass significantly increased the sensitivity and the overall agreement with the PRNT results. Commercially available serological assays are good alternatives to the standard PRNT. However, further studies on larger sample numbers are required for optimization of the assay cutoff values and for evaluation of cost effectiveness. IMPORTANCE Commercial serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available. This study adds new knowledge regarding the optimization of these assays for evaluating postvaccination antibodies status. It highlights the positive and negative aspects of each assay in terms of sensitivity, specificity, and positive and negative predictive values, compared to the gold standard neutralization test. When using serological assays to assess postvaccine immune status, a balance of all parameters needs to be considered and not simply the high specificity. This balance is particularly relevant in the current situation where countries are aiming to mass vaccinate their populations and bring this pandemic under control. Assays with good sensitivity will have a lower percentage of false negatives and thus provide confidence for vaccination. Understanding the strengths and limitations of commercially available serological assays is important, not only for better application of these tests but also to understand the immune response and the duration of protection postvaccination. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557923/ | 180 | 2165-0497 | Microbiology Spectrum | Washington, DC : ASM Press | |
| 16788 | 901 | 치료법 | positive RT-PCR | Term | positive rt-pcr | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 16789 | 901 | 치료법 | reduce | Action | reduce | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 18483 | 901 | 치료법 | positive sample | Term | positive sample | abstract | None | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 30474 | 901 | 치료법 | serological assays | Term | serological assay | author,abstract | 혈청 학적 분석 | 8848 | 10.1128/Spectrum.00733-21 | Serological Assays for Assessing Postvaccination SARS-CoV-2 Antibody Response | Sally A. Mahmoud@@@Subhashini Ganesan@@@Shivaraj Naik@@@Safaa Bissar@@@Isra Al Zamel@@@KN Warren@@@Walid A. Zaher@@@Gulfaraz Khan | 202109 | Research Article | PMC | ABSTRACT Serological assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have crucial applications in the control and surveillance of the current COVID-19 pandemic. A large number of such assays have been developed and are now commercially available. However, there are limited studies evaluating the performance of these tests. We evaluated the performances of the following six commercially available serological assays for detecting SARS-CoV-2 antibodies: (i) Genscript cPass surrogate virus neutralization test (Genscript cPass), (ii) Diasorin-SARS-CoV-2 S1/S2 IgG detection (Diasorin-S1/S2 IgG), (iii) Alinity SARS-CoV-2 IgG II (Alinity IgG II), (iv) Diasorin-SARS-CoV-2 TrimericS IgG (Diasorin-TrimericS IgG), (v) Roche Elecsys anti-SARS-CoV-2-cobas (Roche Elecsys), and (vi) AESKU enzyme linked immunosorbent assay (AESKULISA). The results of these tests were compared against the gold standard plaque reduction neutralization test (PRNT). Roche Elecsys had the highest sensitivity, and the Genscript cPass had the highest specificity. Diasorin-TrimericS IgG had the best overall performance with the highest agreement with the PRNT results. Parallel testing of Genscript cPass with Diasorin-TrimericS IgG and Diasorin-S1/S2 IgG had the optimum performance. Based on the receiver operating characteristic (ROC) curve, lowering the cutoff from 30% to 20% in the Genscript cPass significantly increased the sensitivity and the overall agreement with the PRNT results. Commercially available serological assays are good alternatives to the standard PRNT. However, further studies on larger sample numbers are required for optimization of the assay cutoff values and for evaluation of cost effectiveness. IMPORTANCE Commercial serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available. This study adds new knowledge regarding the optimization of these assays for evaluating postvaccination antibodies status. It highlights the positive and negative aspects of each assay in terms of sensitivity, specificity, and positive and negative predictive values, compared to the gold standard neutralization test. When using serological assays to assess postvaccine immune status, a balance of all parameters needs to be considered and not simply the high specificity. This balance is particularly relevant in the current situation where countries are aiming to mass vaccinate their populations and bring this pandemic under control. Assays with good sensitivity will have a lower percentage of false negatives and thus provide confidence for vaccination. Understanding the strengths and limitations of commercially available serological assays is important, not only for better application of these tests but also to understand the immune response and the duration of protection postvaccination. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557923/ | 180 | 2165-0497 | Microbiology Spectrum | Washington, DC : ASM Press | |
| 16790 | 901 | 치료법 | reported | Action | reported | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 69196 | 901 | 치료법 | T cell responses | Term | t cell response | abstract | T 세포 반응 | 15711 | 10.1111/cei.13627 | Human CD4 + T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential | Johan Verhagen@@@Edith D van der Meijden@@@Vanessa Lang@@@Andreas E Kremer@@@Simon V?lkl@@@Andreas Mackensen@@@Michael Aigner@@@Anita N Kremer | 202109 | Article | PMC | {{{ Abstract }}} !! Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4 + T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4 + T cell therapy of COVID-19. !!{{ Keywords: }} COVID-19; SARS-CoV-2; T cell; T cell receptor; epitope. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239517/ | 362 | 0009-9104 | Clinical and experimental immunology | Oxford : Oxford University Press. | |
| 69197 | 901 | 치료법 | T cells | Cell | t cell | abstract | T세포 | 15711 | 10.1111/cei.13627 | Human CD4 + T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential | Johan Verhagen@@@Edith D van der Meijden@@@Vanessa Lang@@@Andreas E Kremer@@@Simon V?lkl@@@Andreas Mackensen@@@Michael Aigner@@@Anita N Kremer | 202109 | Article | PMC | {{{ Abstract }}} !! Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4 + T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4 + T cell therapy of COVID-19. !!{{ Keywords: }} COVID-19; SARS-CoV-2; T cell; T cell receptor; epitope. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239517/ | 362 | 0009-9104 | Clinical and experimental immunology | Oxford : Oxford University Press. | |
| 69199 | 901 | 치료법 | therapeutic potential | Term | therapeutic potential | title | None | 15711 | 10.1111/cei.13627 | Human CD4 + T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential | Johan Verhagen@@@Edith D van der Meijden@@@Vanessa Lang@@@Andreas E Kremer@@@Simon V?lkl@@@Andreas Mackensen@@@Michael Aigner@@@Anita N Kremer | 202109 | Article | PMC | {{{ Abstract }}} !! Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4 + T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4 + T cell therapy of COVID-19. !!{{ Keywords: }} COVID-19; SARS-CoV-2; T cell; T cell receptor; epitope. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239517/ | 362 | 0009-9104 | Clinical and experimental immunology | Oxford : Oxford University Press. | |
| 69200 | 901 | 치료법 | therapy | Treatment | therapy | abstract | 치료 | 15711 | 10.1111/cei.13627 | Human CD4 + T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential | Johan Verhagen@@@Edith D van der Meijden@@@Vanessa Lang@@@Andreas E Kremer@@@Simon V?lkl@@@Andreas Mackensen@@@Michael Aigner@@@Anita N Kremer | 202109 | Article | PMC | {{{ Abstract }}} !! Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4 + T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4 + T cell therapy of COVID-19. !!{{ Keywords: }} COVID-19; SARS-CoV-2; T cell; T cell receptor; epitope. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239517/ | 362 | 0009-9104 | Clinical and experimental immunology | Oxford : Oxford University Press. | |
| 11087 | 901 | 치료법 | conserved | Term | conserved | title,abstract | None | 2765 | 10.1042/BSR20211491 | Targeting intra-viral conserved nucleocapsid (N) proteins as novel vaccines against SARS-CoVs | Min Thura@@@Joel?Xuan?En Sng@@@Koon?Hwee Ang@@@Jie Li@@@Abhishek Gupta@@@Jimmy?Ming Hong@@@Cheng?William Hong@@@Qi Zeng | 202109 | Virology | PMC | Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic of the Coronavirus disease in late 2019 (COVID-19). Vaccine development efforts have predominantly been aimed at 'Extra-viral' Spike ( S ) protein as vaccine vehicles, but there are concerns regarding ‘viral immune escape’ since multiple mutations may enable the mutated virus strains to escape from immunity against S protein. The ‘Intra-viral’ Nucleocapsid (N-protein) is relatively conserved among mutant strains of coronaviruses during spread and evolution. Herein, we demonstrate novel vaccine candidates against SARS-CoV-2 by using the whole conserved N-protein or its fragment/peptides. Using ELISA assay, we showed that high titers of specific anti-N antibodies (IgG, IgG1, IgG2a, IgM) were maintained for a reasonably long duration (> 5 months), suggesting that N-protein is an excellent immunogen to stimulate host immune system and robust B-cell activation. We synthesized three peptides located at the conserved regions of N-protein among CoVs. One peptide showed as a good immunogen for vaccination as well. Cytokine arrays on post-vaccination mouse sera showed progressive up-regulation of various cytokines such as IFN-γ and CCL5, suggesting that T H 1 associated responses are also stimulated. Furthermore, vaccinated mice exhibited an elevated memory T cells population. Here, we propose an unconventional vaccine strategy targeting the conserved N-protein as an alternative vaccine target for coronaviruses. Moreover, we generated a mouse monoclonal antibody specifically against an epitope shared between SARS-CoV and SARS-CoV-2, and we are currently developing the First-in-Class humanized anti-N-protein antibody to potentially treat patients infected by various CoVs in the future. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463655/ | 132 | 0144-8463 | Bioscience Reports | London : Portland Press on behalf of the Biochemical Society. | |
| 10406 | 901 | 치료법 | performed | Action | performed | abstract | None | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 10407 | 901 | 치료법 | Plasmid | DNA | plasmid | abstract | 플라스미드 | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 10408 | 901 | 치료법 | principle | Term | principle | abstract | None | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 18484 | 901 | 치료법 | Predictive | Term | predictive | abstract | None | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 69201 | 901 | 치료법 | the SARS-CoV-2 virus | Virus | the sars-cov-2 virus | abstract | None | 15711 | 10.1111/cei.13627 | Human CD4 + T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential | Johan Verhagen@@@Edith D van der Meijden@@@Vanessa Lang@@@Andreas E Kremer@@@Simon V?lkl@@@Andreas Mackensen@@@Michael Aigner@@@Anita N Kremer | 202109 | Article | PMC | {{{ Abstract }}} !! Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4 + T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4 + T cell therapy of COVID-19. !!{{ Keywords: }} COVID-19; SARS-CoV-2; T cell; T cell receptor; epitope. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239517/ | 362 | 0009-9104 | Clinical and experimental immunology | Oxford : Oxford University Press. | |
| 69202 | 901 | 치료법 | These data | Gene | these data | abstract | None | 15711 | 10.1111/cei.13627 | Human CD4 + T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential | Johan Verhagen@@@Edith D van der Meijden@@@Vanessa Lang@@@Andreas E Kremer@@@Simon V?lkl@@@Andreas Mackensen@@@Michael Aigner@@@Anita N Kremer | 202109 | Article | PMC | {{{ Abstract }}} !! Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4 + T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4 + T cell therapy of COVID-19. !!{{ Keywords: }} COVID-19; SARS-CoV-2; T cell; T cell receptor; epitope. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239517/ | 362 | 0009-9104 | Clinical and experimental immunology | Oxford : Oxford University Press. | |
| 69203 | 901 | 치료법 | Treatment | Treatment | treatment | abstract | 치료 | 15711 | 10.1111/cei.13627 | Human CD4 + T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential | Johan Verhagen@@@Edith D van der Meijden@@@Vanessa Lang@@@Andreas E Kremer@@@Simon V?lkl@@@Andreas Mackensen@@@Michael Aigner@@@Anita N Kremer | 202109 | Article | PMC | {{{ Abstract }}} !! Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4 + T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4 + T cell therapy of COVID-19. !!{{ Keywords: }} COVID-19; SARS-CoV-2; T cell; T cell receptor; epitope. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239517/ | 362 | 0009-9104 | Clinical and experimental immunology | Oxford : Oxford University Press. | |
| 69204 | 901 | 치료법 | Vaccine | Drug | vaccine | abstract | 백신 | 15711 | 10.1111/cei.13627 | Human CD4 + T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential | Johan Verhagen@@@Edith D van der Meijden@@@Vanessa Lang@@@Andreas E Kremer@@@Simon V?lkl@@@Andreas Mackensen@@@Michael Aigner@@@Anita N Kremer | 202109 | Article | PMC | {{{ Abstract }}} !! Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4 + T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4 + T cell therapy of COVID-19. !!{{ Keywords: }} COVID-19; SARS-CoV-2; T cell; T cell receptor; epitope. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239517/ | 362 | 0009-9104 | Clinical and experimental immunology | Oxford : Oxford University Press. | |
| 18485 | 901 | 치료법 | protocol | Term | protocol | abstract | 프로토콜 | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 69205 | 901 | 치료법 | while | Term | while | abstract | None | 15711 | 10.1111/cei.13627 | Human CD4 + T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential | Johan Verhagen@@@Edith D van der Meijden@@@Vanessa Lang@@@Andreas E Kremer@@@Simon V?lkl@@@Andreas Mackensen@@@Michael Aigner@@@Anita N Kremer | 202109 | Article | PMC | {{{ Abstract }}} !! Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4 + T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4 + T cell therapy of COVID-19. !!{{ Keywords: }} COVID-19; SARS-CoV-2; T cell; T cell receptor; epitope. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239517/ | 362 | 0009-9104 | Clinical and experimental immunology | Oxford : Oxford University Press. | |
| 10409 | 901 | 치료법 | proof | Term | proof | abstract | None | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 18486 | 901 | 치료법 | reaction | Term | reaction | abstract | None | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 10410 | 901 | 치료법 | Protein | Protein | protein | abstract | 단백질 | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 106691 | 901 | 치료법 | provided | Action | provided | abstract | None | 34774 | 10.1016/j.ejogrb.2021.10.007 | Treatment of COVID-19 in pregnant women: A systematic review and meta-analysis | Steven Giesbers@@@Edwina Goh@@@Tania Kew@@@John Allotey@@@Vanessa Brizuela@@@Edna Kara@@@Heinke Kunst@@@Mercedes Bonet@@@Shakila Thangaratinam | 202112 | Review article | Sciencedirect | Abstract!!Objective!!Clinical trials evaluating pharmacological and non-pharmacological treatment of COVID-19, either excluded pregnant women or included very few women. Unlike the numerous systematic reviews on prevalence, symptoms and adverse outcomes of COVID-19 in pregnancy, there are very few on the effects of treatment on maternal and neonatal outcomes in pregnancy. We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes.!!Data sources!!We performed a systematic literature search of the following databases: Medline, Embase, Cochrane database, WHO (World Health Organization) COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 1 December 2020.!!Study eligibility criteria!!Studies were only included if they involved pregnant or postnatal women who were exposed to pregnancy specific interventions like the mode of delivery and type of anaesthesia, pharmacological or non-pharmacological interventions.!!Study appraisal and synthesis methods!!We first screened the titles and abstracts of studies and then assessed the full text of the selected studies in detail for eligibility. Data on study design, population, type of screening for COVID-19, country, hospital, country status (high or low and middle income), treatment given (mode of delivery, type of anaesthesia, type of pharmacological and non-pharmacological treatment was extracted. The pre-defined maternal outcomes we collected were mode of delivery (vaginal or by caesarean section), severe or critical COVID-19 (as defined by the authors), symptomatic COVID-19, maternal death, maternal hospital admission, ICU admission, mechanical ventilation, ECMO and maternal pneumonia. The pre-defined neonatal outcomes we extracted were preterm birth (<37?weeks), stillbirth, neonatal death, NICU admission, neonatal COVID-19 positive, neonatal acidosis (pH?<?7.0) and Apgar scores (<8 after 5?min). Study quality assessment was performed.!!Results!!From a total of 342 potential eligible studies, we included 27 studies in our systematic review, including 4943 pregnant women (appendix 3). Sixteen studies had a retrospective cohort design and 11 a prospective cohort design. There were no randomised controlled trials. There was a significant association between caesarean section and admission to ICU (OR 4.99, 95% CI 1.24 to 20.12; 4 studies, 153 women, I2?=?0%), and diagnosis of maternal COVID-19 pneumonia as defined by study authors (OR 3.09, 95% CI 1.52 to 6.28; 2 studies, 228 women, I2?=?0%). Women who had a preterm birth were more likely to have the baby via caesarean section (OR 3.03, 95% CI 1.71 to 5.36, 12 studies; 314 women, I2?=?0%). For pharmacological and non-pharmacological we provided estimates of the expected rates of outcomes in women exposed to various treatment of COVID-19. Comparative data for pregnant women, in particular for treatments proven to be effective in the general population, however, is lacking to provide clinically meaningful interpretation.!!Conclusions!!We found associations for pregnancy specific interventions, like mode of delivery and outcomes of the disease, but there were too few data on pharmacological and non-pharmacological treatments in pregnant women with COVID-19. We report the rates of complications found in the literature. We encourage researchers to include pregnant women in their trials and report the data on pregnant women separately. | https://doi.org/10.1016/j.ejogrb.2021.10.007 | 1121 | 0301-2115 | European journal of obstetrics, gynecology, and re | Limerick : Elsevier Scientific Publishers. | |
| 106697 | 901 | 치료법 | selected | Action | selected | abstract | None | 34774 | 10.1016/j.ejogrb.2021.10.007 | Treatment of COVID-19 in pregnant women: A systematic review and meta-analysis | Steven Giesbers@@@Edwina Goh@@@Tania Kew@@@John Allotey@@@Vanessa Brizuela@@@Edna Kara@@@Heinke Kunst@@@Mercedes Bonet@@@Shakila Thangaratinam | 202112 | Review article | Sciencedirect | Abstract!!Objective!!Clinical trials evaluating pharmacological and non-pharmacological treatment of COVID-19, either excluded pregnant women or included very few women. Unlike the numerous systematic reviews on prevalence, symptoms and adverse outcomes of COVID-19 in pregnancy, there are very few on the effects of treatment on maternal and neonatal outcomes in pregnancy. We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes.!!Data sources!!We performed a systematic literature search of the following databases: Medline, Embase, Cochrane database, WHO (World Health Organization) COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 1 December 2020.!!Study eligibility criteria!!Studies were only included if they involved pregnant or postnatal women who were exposed to pregnancy specific interventions like the mode of delivery and type of anaesthesia, pharmacological or non-pharmacological interventions.!!Study appraisal and synthesis methods!!We first screened the titles and abstracts of studies and then assessed the full text of the selected studies in detail for eligibility. Data on study design, population, type of screening for COVID-19, country, hospital, country status (high or low and middle income), treatment given (mode of delivery, type of anaesthesia, type of pharmacological and non-pharmacological treatment was extracted. The pre-defined maternal outcomes we collected were mode of delivery (vaginal or by caesarean section), severe or critical COVID-19 (as defined by the authors), symptomatic COVID-19, maternal death, maternal hospital admission, ICU admission, mechanical ventilation, ECMO and maternal pneumonia. The pre-defined neonatal outcomes we extracted were preterm birth (<37?weeks), stillbirth, neonatal death, NICU admission, neonatal COVID-19 positive, neonatal acidosis (pH?<?7.0) and Apgar scores (<8 after 5?min). Study quality assessment was performed.!!Results!!From a total of 342 potential eligible studies, we included 27 studies in our systematic review, including 4943 pregnant women (appendix 3). Sixteen studies had a retrospective cohort design and 11 a prospective cohort design. There were no randomised controlled trials. There was a significant association between caesarean section and admission to ICU (OR 4.99, 95% CI 1.24 to 20.12; 4 studies, 153 women, I2?=?0%), and diagnosis of maternal COVID-19 pneumonia as defined by study authors (OR 3.09, 95% CI 1.52 to 6.28; 2 studies, 228 women, I2?=?0%). Women who had a preterm birth were more likely to have the baby via caesarean section (OR 3.03, 95% CI 1.71 to 5.36, 12 studies; 314 women, I2?=?0%). For pharmacological and non-pharmacological we provided estimates of the expected rates of outcomes in women exposed to various treatment of COVID-19. Comparative data for pregnant women, in particular for treatments proven to be effective in the general population, however, is lacking to provide clinically meaningful interpretation.!!Conclusions!!We found associations for pregnancy specific interventions, like mode of delivery and outcomes of the disease, but there were too few data on pharmacological and non-pharmacological treatments in pregnant women with COVID-19. We report the rates of complications found in the literature. We encourage researchers to include pregnant women in their trials and report the data on pregnant women separately. | https://doi.org/10.1016/j.ejogrb.2021.10.007 | 1121 | 0301-2115 | European journal of obstetrics, gynecology, and re | Limerick : Elsevier Scientific Publishers. | |
| 10411 | 901 | 치료법 | reduced | Action | reduced | abstract | None | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 18487 | 901 | 치료법 | reagent | Term | reagent | abstract | None | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 18490 | 901 | 치료법 | reverse transcriptase | Term | reverse transcriptase | abstract | None | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 18491 | 901 | 치료법 | robust | Term | robust | abstract | None | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 16791 | 901 | 치료법 | reported symptoms | Symptom | reported symptom | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 18589 | 901 | 치료법 | IgG antibody | Term | igg antibody | abstract | IgG 항체 | 6537 | 10.1371/journal.pone.0257743 | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence: Navigating the absence of a gold standard | Sahar Saeed@@@Sheila F. O’Brien@@@Kento Abe@@@Qi-Long Yi@@@Bhavisha Rathod@@@Jenny Wang@@@Mahya Fazel-Zarandi@@@Ashleigh Tuite@@@David Fisman@@@Heidi Wood@@@Karen Colwill@@@Anne-Claude Gingras@@@Steven J. Drews | 202109 | Research Article | PMC | Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence studies bridge the gap left from case detection, to estimate the true burden of the COVID-19 pandemic. While multiple anti-SARS-CoV-2 immunoassays are available, no gold standard exists. Methods This serial cross-sectional study was conducted using plasma samples from 8999 healthy blood donors between April-September 2020. Each sample was tested by four assays: Abbott SARS-Cov-2 IgG assay, targeting nucleocapsid (Abbott-NP) and three in-house IgG ELISA assays (targeting spike glycoprotein, receptor binding domain, and nucleocapsid). Seroprevalence rates were compared using multiple composite reference standards and by a series of Bayesian Latent Class Models. Result We found 13 unique diagnostic phenotypes; only 32 samples (0.4%) were positive by all assays. None of the individual assays resulted in seroprevalence increasing monotonically over time. In contrast, by using the results from all assays, the Bayesian Latent Class Model with informative priors predicted seroprevalence increased from 0.7% (95% credible interval (95% CrI); 0.4, 1.0%) in April/May to 0.7% (95% CrI 0.5, 1.1%) in June/July to 0.9% (95% CrI 0.5, 1.3) in August/September. Assay characteristics varied over time. Overall Spike had the highest sensitivity (93.5% (95% CrI 88.7, 97.3%), while the sensitivity of the Abbott-NP assay waned from 77.3% (95% CrI 58.7, 92.5%) in April/May to 64.4% (95% CrI 45.6, 83.0) by August/September. Discussion Our results confirmed very low seroprevalence after the first wave in Canada. Given the dynamic nature of this pandemic, Bayesian Latent Class Models can be used to correct for imperfect test characteristics and waning IgG antibody signals. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459951/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 79771 | 901 | 치료법 | Hospitalization | Term | hospitalization | abstract | 입원 | 16014 | 10.1016/j.dsx.2022.102396 | An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19 | Awadhesh Kumar Singh@@@Akriti Singh@@@Ritu Singh@@@Anoop Misra | 202202 | Clinical Trial | PMC | {{{ Abstract }}} !!{{ Background and aims: }} Molnupiravir is a newer oral antiviral drug that has recently received emergency use authorization (EUA) in USA, UK and India. We aim to conduct an update on our previous systematic review to provide practical clinical guideline for using molnupiravir in patients with COVID-19. !!{{ Methods: }} We systematically searched the electronic database of PubMed, MedRxiv and Google Scholar until January 5, 2022, using key MeSH keywords. !!{{ Results: }} Final result of phase 3 study in 1433 non-hospitalized COVID-19 patients showed a significant reduction in composite risk of hospital admission or death (absolute risk difference, -3.0% [95% confidence interval {CI}, -5.9 to -0.1%]; 1-sided P = 0.02) although with a non-significant 31% relative risk reduction (RRR). RRR for death alone was 89% (95% CI, 14 to 99; P-value not reported). Number needed to treat to prevent 1 death or 1 hospitalization or death composite appears to be closely competitive to other agents having EUA in people with COVID-19. However, cost-wise molnupiravir is comparatively cheaper compared to all other agents. !!{{ Conclusion: }} Molnupiravir could be a useful agent in non-pregnant unvaccinated adults with COVID-19 who are at increased risk of severity including hospitalization. However, it is effective only when used within 5-days of onset of symptoms. A 5-days course seems to be safe without any obvious short-term side effects. !!{{ Keywords: }} Bamlanivimab?etesevimab; COVID-19; Casirivimab?imdevimab; Molnupiravir; Nirmatrelvir-ritonavir; Remdesivir; SARS-CoV-2; Sotrovimab. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755553/ | 927 | 1871-4021 | Diabetes & metabolic syndrome | Amsterdam : Elsevier Ltd. | |
| 10412 | 901 | 치료법 | Remdesivir | Drug | remdesivir | abstract | 렘데시비르 | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 118793 | 901 | 치료법 | Retrospective analysis | Term | retrospective analysis | abstract | 후 향적 분석 | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 118794 | 901 | 치료법 | severe COVID-19 | Disease | severe covid-19 | abstract | 심한 코비드 -19 | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 69688 | 901 | 치료법 | binding free energy | Term | binding free energy | abstract | 결합 자유 에너지 | 15721 | 10.1080/07391102.2020.1778536 | Virtual screening and dynamics of potential inhibitors targeting RNA binding domain of nucleocapsid phosphoprotein from SARS-CoV-2 | Rohitash Yadav@@@Mohammed Imran@@@Puneet Dhamija@@@Kapil Suchal@@@Shailendra Handu | 202108 | Article | PMC | {{{ Abstract }}} !! The emergence of the coronavirus disease-2019 pandemic has led to an outbreak in the world. The SARS-CoV-2 is seventh and latest in coronavirus family with unique exonucleases for repairing any mismatches in newly transcribed genetic material. Therefore, drugs with novel additional mechanisms are required to simultaneously target and eliminate the virus. Thus, a newly deciphered N protein is taken as a target that belongs to SARS-CoV-2. They play a vital role in RNA transcription, viral replication and new virion formation. This study used virtual screening, molecular modeling and docking of the 8987 ligands from Asinex and PubChem databases against this novel target protein. Three hotspot sites having DScore ≥1 (Site 1, Site 2 and Site 3) for ligand binding were selected. Subsequently, high throughput screening, standard precision and extra precision docking process and molecular dynamics concluded three best drugs from two libraries. Two antiviral moieties from Asinex databases (5817 and 6799) have docking scores of -10.29 and -10.156; along with their respective free binding energies (Δ G bind) of -51.96 and -64.36 on Site 3. The third drug, Zidovudine, is from PubChem database with docking scores of -9.75 with its binding free energies (Δ G bind) of -59.43 on Site 3. The RMSD and RMSF were calculated for all the three drugs through molecular dynamics simulation studies for 50 ns. Zidovudine shows a very stable interaction with fluctuation starting at 2.4 ? on 2 ns and remained stable at 3 ? from 13 to 50 ns. Thus, paving the way for further biological validation as a potential treatment.Communicated by Ramaswamy H. Sarma. !!{{ Keywords: }} COVID-19; SARS-CoV-2; docking; molecular dynamics; nucleocapsid phosphoprotein. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332875/ | 219 | 0739-1102 | Journal of biomolecular structure & dynamics | June 2012- : Oxon, UK : Taylor & Francis. | |
| 118795 | 901 | 치료법 | severe disease | Disease | severe disease | abstract | None | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 69689 | 901 | 치료법 | calculated | Action | calculated | abstract | None | 15721 | 10.1080/07391102.2020.1778536 | Virtual screening and dynamics of potential inhibitors targeting RNA binding domain of nucleocapsid phosphoprotein from SARS-CoV-2 | Rohitash Yadav@@@Mohammed Imran@@@Puneet Dhamija@@@Kapil Suchal@@@Shailendra Handu | 202108 | Article | PMC | {{{ Abstract }}} !! The emergence of the coronavirus disease-2019 pandemic has led to an outbreak in the world. The SARS-CoV-2 is seventh and latest in coronavirus family with unique exonucleases for repairing any mismatches in newly transcribed genetic material. Therefore, drugs with novel additional mechanisms are required to simultaneously target and eliminate the virus. Thus, a newly deciphered N protein is taken as a target that belongs to SARS-CoV-2. They play a vital role in RNA transcription, viral replication and new virion formation. This study used virtual screening, molecular modeling and docking of the 8987 ligands from Asinex and PubChem databases against this novel target protein. Three hotspot sites having DScore ≥1 (Site 1, Site 2 and Site 3) for ligand binding were selected. Subsequently, high throughput screening, standard precision and extra precision docking process and molecular dynamics concluded three best drugs from two libraries. Two antiviral moieties from Asinex databases (5817 and 6799) have docking scores of -10.29 and -10.156; along with their respective free binding energies (Δ G bind) of -51.96 and -64.36 on Site 3. The third drug, Zidovudine, is from PubChem database with docking scores of -9.75 with its binding free energies (Δ G bind) of -59.43 on Site 3. The RMSD and RMSF were calculated for all the three drugs through molecular dynamics simulation studies for 50 ns. Zidovudine shows a very stable interaction with fluctuation starting at 2.4 ? on 2 ns and remained stable at 3 ? from 13 to 50 ns. Thus, paving the way for further biological validation as a potential treatment.Communicated by Ramaswamy H. Sarma. !!{{ Keywords: }} COVID-19; SARS-CoV-2; docking; molecular dynamics; nucleocapsid phosphoprotein. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332875/ | 219 | 0739-1102 | Journal of biomolecular structure & dynamics | June 2012- : Oxon, UK : Taylor & Francis. | |
| 69690 | 901 | 치료법 | coronavirus | Virus | coronavirus | abstract | 코로나바이러스 | 15721 | 10.1080/07391102.2020.1778536 | Virtual screening and dynamics of potential inhibitors targeting RNA binding domain of nucleocapsid phosphoprotein from SARS-CoV-2 | Rohitash Yadav@@@Mohammed Imran@@@Puneet Dhamija@@@Kapil Suchal@@@Shailendra Handu | 202108 | Article | PMC | {{{ Abstract }}} !! The emergence of the coronavirus disease-2019 pandemic has led to an outbreak in the world. The SARS-CoV-2 is seventh and latest in coronavirus family with unique exonucleases for repairing any mismatches in newly transcribed genetic material. Therefore, drugs with novel additional mechanisms are required to simultaneously target and eliminate the virus. Thus, a newly deciphered N protein is taken as a target that belongs to SARS-CoV-2. They play a vital role in RNA transcription, viral replication and new virion formation. This study used virtual screening, molecular modeling and docking of the 8987 ligands from Asinex and PubChem databases against this novel target protein. Three hotspot sites having DScore ≥1 (Site 1, Site 2 and Site 3) for ligand binding were selected. Subsequently, high throughput screening, standard precision and extra precision docking process and molecular dynamics concluded three best drugs from two libraries. Two antiviral moieties from Asinex databases (5817 and 6799) have docking scores of -10.29 and -10.156; along with their respective free binding energies (Δ G bind) of -51.96 and -64.36 on Site 3. The third drug, Zidovudine, is from PubChem database with docking scores of -9.75 with its binding free energies (Δ G bind) of -59.43 on Site 3. The RMSD and RMSF were calculated for all the three drugs through molecular dynamics simulation studies for 50 ns. Zidovudine shows a very stable interaction with fluctuation starting at 2.4 ? on 2 ns and remained stable at 3 ? from 13 to 50 ns. Thus, paving the way for further biological validation as a potential treatment.Communicated by Ramaswamy H. Sarma. !!{{ Keywords: }} COVID-19; SARS-CoV-2; docking; molecular dynamics; nucleocapsid phosphoprotein. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332875/ | 219 | 0739-1102 | Journal of biomolecular structure & dynamics | June 2012- : Oxon, UK : Taylor & Francis. | |
| 79635 | 901 | 치료법 | elevated | Action | elevated | abstract | None | 15973 | 10.1016/j.mehy.2020.110468 | The plausible mechanisms of tramadol for treatment of COVID-19 | Nahla E El-Ashmawy@@@Abdel-Halim A Lashin@@@Kamal M Okasha@@@Amal M Abo Kamer@@@Tarek M Mostafa@@@Mona El-Aasr@@@Ahmed E Goda@@@Yusuf A Haggag@@@Haytham O Tawfik@@@Mariam A Abo-Saif | 202101 | Review | PMC | {{{ Abstract }}} !! Currently, no single medication has been approved for the management of coronavirus disease-2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, drug repositioningby investigating the use of existing drugs for management of COVID-19 patients is considered a desperate need. Tramadol is a commonly prescribed analgesic drug for treatment of moderate to severe pain with less potential for dependence and respiratory depression. Multiple evidence support that tramadol is a promising drug for treatment of COVID-19 patients. Herein, we discuss the possible beneficial effects of using tramadol against SARS-CoV-2 infection and their underlying mechanism of action. The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Besides, tramadol activates natural killer (NK) and T-cells and enhances IL-2 secretion, which produce immune-enhancing effect against SARS-CoV-2. Recent studies confirmed that COVID-19 patients with acute respiratory failure showed increased fibrin formation and polymerization that may lead to thrombosis. Tramadol owing to its hypocoagulable effect may protect against venous thromboembolism in these patients. Moreover, tramadol can exert a cardioprotective effect via decreasing lactate dehydrogenase (LDH) level which is elevated in most of patients with COVID-19. Furthermore, the severity and mortality of COVID-19 have been correlated with old age patients, which may be due to the lack of antioxidant mechanisms and increased oxidative damage. Tramadol could protect COVID-19 patient from disease complications by increases the antioxidant enzymes superoxide dismutase and glutathione peroxidase while diminished malondialdehyde. More interestingly, tramadol as an effective analgesic and antitussive may have a beneficial effect on COVID-19 patients suffering from cough, headache, ache, and pain. The tramadol anti-psychotic effect may also protect against psychiatric disorders associated with SARS-CoV-2 infection. Moreover, tramadol has bactericidal activity against a wide range of pathogens including Pseudomonas aeruginosa which is common in severe COVID-19 patients leading to pneumonia with worse clinical outcomes. Therefore, we hypothesize that tramadol might be a promising adjuvant therapeutic option against SARS-CoV-2 infection. Based on that, tramadol should be considered as adjuvant therapy for COVID-19 clinical trials. !!{{ Keywords: }} Anti-inflammatory; COVID-19; Hypocoagulable effect; Immune-enhancing; SARS-CoV-2; Tramadol. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831961/ | 2493 | 0306-9877 | Medical Hypotheses | Penrith, Eng., Eden Press. | |
| 79636 | 901 | 치료법 | ENhance | Action | enhance | abstract | None | 15973 | 10.1016/j.mehy.2020.110468 | The plausible mechanisms of tramadol for treatment of COVID-19 | Nahla E El-Ashmawy@@@Abdel-Halim A Lashin@@@Kamal M Okasha@@@Amal M Abo Kamer@@@Tarek M Mostafa@@@Mona El-Aasr@@@Ahmed E Goda@@@Yusuf A Haggag@@@Haytham O Tawfik@@@Mariam A Abo-Saif | 202101 | Review | PMC | {{{ Abstract }}} !! Currently, no single medication has been approved for the management of coronavirus disease-2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, drug repositioningby investigating the use of existing drugs for management of COVID-19 patients is considered a desperate need. Tramadol is a commonly prescribed analgesic drug for treatment of moderate to severe pain with less potential for dependence and respiratory depression. Multiple evidence support that tramadol is a promising drug for treatment of COVID-19 patients. Herein, we discuss the possible beneficial effects of using tramadol against SARS-CoV-2 infection and their underlying mechanism of action. The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Besides, tramadol activates natural killer (NK) and T-cells and enhances IL-2 secretion, which produce immune-enhancing effect against SARS-CoV-2. Recent studies confirmed that COVID-19 patients with acute respiratory failure showed increased fibrin formation and polymerization that may lead to thrombosis. Tramadol owing to its hypocoagulable effect may protect against venous thromboembolism in these patients. Moreover, tramadol can exert a cardioprotective effect via decreasing lactate dehydrogenase (LDH) level which is elevated in most of patients with COVID-19. Furthermore, the severity and mortality of COVID-19 have been correlated with old age patients, which may be due to the lack of antioxidant mechanisms and increased oxidative damage. Tramadol could protect COVID-19 patient from disease complications by increases the antioxidant enzymes superoxide dismutase and glutathione peroxidase while diminished malondialdehyde. More interestingly, tramadol as an effective analgesic and antitussive may have a beneficial effect on COVID-19 patients suffering from cough, headache, ache, and pain. The tramadol anti-psychotic effect may also protect against psychiatric disorders associated with SARS-CoV-2 infection. Moreover, tramadol has bactericidal activity against a wide range of pathogens including Pseudomonas aeruginosa which is common in severe COVID-19 patients leading to pneumonia with worse clinical outcomes. Therefore, we hypothesize that tramadol might be a promising adjuvant therapeutic option against SARS-CoV-2 infection. Based on that, tramadol should be considered as adjuvant therapy for COVID-19 clinical trials. !!{{ Keywords: }} Anti-inflammatory; COVID-19; Hypocoagulable effect; Immune-enhancing; SARS-CoV-2; Tramadol. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831961/ | 2493 | 0306-9877 | Medical Hypotheses | Penrith, Eng., Eden Press. | |
| 118796 | 901 | 치료법 | severe inflammation | Symptom | severe inflammation | abstract | None | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 16792 | 901 | 치료법 | respiratory | Term | respiratory | abstract | 호흡기 | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 16793 | 901 | 치료법 | respiratory symptoms | Symptom | respiratory symptom | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 16794 | 901 | 치료법 | Result | Term | result | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 16795 | 901 | 치료법 | retrospective cohort study | Term | retrospective cohort study | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 16796 | 901 | 치료법 | rhinitis | Term | rhinitis | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 29893 | 901 | 치료법 | Spread | Term | spread | abstract | 확산 | 8821 | 10.1128/Spectrum.00680-21 | Validation of Commercial SARS-CoV-2 Immunoassays in a Nigerian Population | Fehintola Ige@@@Yohhei Hamada@@@Laura Steinhardt@@@Nnaemeka C. Iriemenam@@@Mabel Uwandu@@@Stacie Marta Greby@@@Maureen Aniedobe@@@Babatunde Lawal Salako@@@Molebogeng X. Rangaka@@@Ibrahim Abubakar@@@Rosemary Audu | 202110 | Research Article | PMC | ABSTRACT Validated assays are essential for reliable serosurveys; however, most SARS-CoV-2 immunoassays have been validated using specimens from China, Europe, or U.S. populations. We evaluated the performance of five commercial SARS-CoV-2 immunoassays to inform their use in serosurveys in Nigeria. Four semiquantitative enzyme-linked immunosorbent assays (ELISAs) (Euroimmun anti-SARS-CoV-2 nucleocapsid protein [NCP] immunoglobulin G [IgG], Euroimmun spike SARS-CoV-2 IgG, Mologic Omega COVID-19 IgG, Bio-Rad Platelia SARS-CoV-2 Total Ab) and one chemiluminescent microparticle immunoassay (Abbott Architect SARS-CoV-2 IgG) were evaluated. We estimated the analytical performance characteristics using plasma from 100 SARS-CoV-2 PCR-positive patients from varied time points post-PCR confirmation and 100 prepandemic samples (50 HIV positive and 50 hepatitis B positive). The Bio-Rad assay failed the manufacturer-specified validation steps. The Euroimmun NCP, Euroimmun spike, and Mologic assays had sensitivities of 73.7%, 74.4%, and 76.9%, respectively, on samples taken 15 to 58?days after PCR confirmation and specificities of 97%, 100%, and 83.8%, respectively. The Abbott assay had 71.3% sensitivity and 100% specificity on the same panel. Parallel or serial algorithms combining two tests did not substantially improve the sensitivity or specificity. Our results showed lower sensitivity and, for one immunoassay, lower specificity compared to the manufacturers’ results and other reported validations. Seroprevalence estimates using these assays might need to be interpreted with caution in Nigeria and similar settings. These findings highlight the importance of in-country validations of SARS-CoV-2 serological assays prior to use to ensure that accurate results are available for public health decision-making to control the COVID-19 pandemic in Africa. IMPORTANCE This study used positive and negative sample panels from Nigeria to test the performance of several commercially available SARS-CoV-2 serological assays. Using these prepandemic and SARS-CoV-2-positive samples, we found much lower levels of sensitivity in four commercially available assays than most assay manufacturer reports and independent evaluations. The use of these assays with suboptimal sensitivity and specificity in Nigeria or countries with population exposure to similar endemic pathogens could lead to a biased estimate of the seroprevalence, over- or underestimating the true disease prevalence, and limit efforts to stop the spread of SARS-CoV-2. It is important to conduct in-country validations of serological SARS-CoV-2 assays prior to their widespread use, especially in countries with limited representation in published assay validations. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510257/ | 180 | 2165-0497 | Microbiology Spectrum | Washington, DC : ASM Press | |
| 30330 | 901 | 치료법 | Sensitivity and specificity | Term | sensitivity and specificity | abstract | 민감도와 특이성 | 8838 | 10.1128/spectrum.00591-21 | Accuracy of Real-Time Polymerase Chain Reaction in COVID-19 Patients | Merlin Jayalal Lawrence Panchali@@@Hyeon Jeong Oh@@@You Mi Lee@@@Choon-Mee Kim@@@Misbah Tariq@@@Jun-Won Seo@@@Da Young Kim@@@Na Ra Yun@@@Dong-Min Kim | 202202 | Research Article | PMC | ABSTRACT Coronavirus disease 2019 (COVID-19) is a mild to severe respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diagnostic accuracy of the Centers for Disease Control and Prevention (CDC)- or World Health Organization (WHO)-recommended real-time PCR (RT-qPCR) primers in clinical practice remains unproven. We conducted a prospective study on the accuracy of RT-qPCR using an in-house?designed primer set (iNP) targeting the nucleocapsid protein as well as various recommended and commercial primers. The accuracy was assessed by culturing or seroconversion. We enrolled 12 confirmed COVID-19 patients with a total of 590 clinical samples. When a cutoff value of the cycle threshold (C t ) was set to 35, RT-qPCRs with WHO RdRp primers and CDC N1, N2, and N3 primers showed sensitivity of 42.1% to 63.2% and specificity of 90.5% to 100% in sputum, and sensitivity of 65.2% to 69.6% and specificity of 65.2% to 69.6% in nasopharyngeal samples. The sensitivity and specificity of iNP RT-qPCR in sputum and nasopharyngeal samples were 94.8%/100% and 69.6%/100%, respectively. Sputum testing had the highest sensitivity, followed by nasopharyngeal testing ( P?= 0.0193); self-collected saliva samples yielded better characteristics than oropharyngeal samples ( P?= 0.0032). Our results suggest that iNP RT-qPCR has better sensitivity and specificity than RT-PCR with WHO ( P?< 0.0001) or CDC (N1: P?= 0.0012, N2: P?= 0.0013, N3: P?= 0.0012) primers. Sputum RT-qPCR analysis has the highest sensitivity, followed by nasopharyngeal, saliva, and oropharyngeal assays. Our study suggests that considerable improvement is needed for the RT-qPCR WHO and CDC primer sets for detecting SARS-CoV-2. IMPORTANCE Numerous research campaigns have addressed the vast majority of clinical and diagnostic specificity and sensitivity of various primer sets of SARS-CoV2 viral detection. Despite the impressive progress made to resolve the pandemic, there is still a need for continuous and active improvement of primers used for diagnosis in clinical practice. Our study significantly exceeds the scale of previously published research on the specificity and sensitivity of different primers comparing with different specimens and is the most comprehensive to date in terms of constant monitoring of primer sets of current usage. Henceforth, our results suggest that sputum samples sensitivity is the highest, followed by nasopharyngeal, saliva, and oropharyngeal samples. The CDC recommends the use of oropharyngeal specimens, leading to certain discrepancy between the guidelines set forth by the CDC and IDSA. We proved that the oropharyngeal samples demonstrated the lowest sensitivity for the detection of SARS-CoV-2. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849071/ | 180 | 2165-0497 | Microbiology Spectrum | Washington, DC : ASM Press | |
| 18492 | 901 | 치료법 | RT-PCR | Term | rt-pcr | abstract | 실시간 중합효소연쇄반응 | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 18493 | 901 | 치료법 | RT-PCR assay | Term | rt-pcr assay | abstract | RT-PCR 검사 | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 29894 | 901 | 치료법 | Total | Term | total | abstract | None | 8821 | 10.1128/Spectrum.00680-21 | Validation of Commercial SARS-CoV-2 Immunoassays in a Nigerian Population | Fehintola Ige@@@Yohhei Hamada@@@Laura Steinhardt@@@Nnaemeka C. Iriemenam@@@Mabel Uwandu@@@Stacie Marta Greby@@@Maureen Aniedobe@@@Babatunde Lawal Salako@@@Molebogeng X. Rangaka@@@Ibrahim Abubakar@@@Rosemary Audu | 202110 | Research Article | PMC | ABSTRACT Validated assays are essential for reliable serosurveys; however, most SARS-CoV-2 immunoassays have been validated using specimens from China, Europe, or U.S. populations. We evaluated the performance of five commercial SARS-CoV-2 immunoassays to inform their use in serosurveys in Nigeria. Four semiquantitative enzyme-linked immunosorbent assays (ELISAs) (Euroimmun anti-SARS-CoV-2 nucleocapsid protein [NCP] immunoglobulin G [IgG], Euroimmun spike SARS-CoV-2 IgG, Mologic Omega COVID-19 IgG, Bio-Rad Platelia SARS-CoV-2 Total Ab) and one chemiluminescent microparticle immunoassay (Abbott Architect SARS-CoV-2 IgG) were evaluated. We estimated the analytical performance characteristics using plasma from 100 SARS-CoV-2 PCR-positive patients from varied time points post-PCR confirmation and 100 prepandemic samples (50 HIV positive and 50 hepatitis B positive). The Bio-Rad assay failed the manufacturer-specified validation steps. The Euroimmun NCP, Euroimmun spike, and Mologic assays had sensitivities of 73.7%, 74.4%, and 76.9%, respectively, on samples taken 15 to 58?days after PCR confirmation and specificities of 97%, 100%, and 83.8%, respectively. The Abbott assay had 71.3% sensitivity and 100% specificity on the same panel. Parallel or serial algorithms combining two tests did not substantially improve the sensitivity or specificity. Our results showed lower sensitivity and, for one immunoassay, lower specificity compared to the manufacturers’ results and other reported validations. Seroprevalence estimates using these assays might need to be interpreted with caution in Nigeria and similar settings. These findings highlight the importance of in-country validations of SARS-CoV-2 serological assays prior to use to ensure that accurate results are available for public health decision-making to control the COVID-19 pandemic in Africa. IMPORTANCE This study used positive and negative sample panels from Nigeria to test the performance of several commercially available SARS-CoV-2 serological assays. Using these prepandemic and SARS-CoV-2-positive samples, we found much lower levels of sensitivity in four commercially available assays than most assay manufacturer reports and independent evaluations. The use of these assays with suboptimal sensitivity and specificity in Nigeria or countries with population exposure to similar endemic pathogens could lead to a biased estimate of the seroprevalence, over- or underestimating the true disease prevalence, and limit efforts to stop the spread of SARS-CoV-2. It is important to conduct in-country validations of serological SARS-CoV-2 assays prior to their widespread use, especially in countries with limited representation in published assay validations. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510257/ | 180 | 2165-0497 | Microbiology Spectrum | Washington, DC : ASM Press | |
| 29895 | 901 | 치료법 | validation | Term | validation | author | 확인 | 8821 | 10.1128/Spectrum.00680-21 | Validation of Commercial SARS-CoV-2 Immunoassays in a Nigerian Population | Fehintola Ige@@@Yohhei Hamada@@@Laura Steinhardt@@@Nnaemeka C. Iriemenam@@@Mabel Uwandu@@@Stacie Marta Greby@@@Maureen Aniedobe@@@Babatunde Lawal Salako@@@Molebogeng X. Rangaka@@@Ibrahim Abubakar@@@Rosemary Audu | 202110 | Research Article | PMC | ABSTRACT Validated assays are essential for reliable serosurveys; however, most SARS-CoV-2 immunoassays have been validated using specimens from China, Europe, or U.S. populations. We evaluated the performance of five commercial SARS-CoV-2 immunoassays to inform their use in serosurveys in Nigeria. Four semiquantitative enzyme-linked immunosorbent assays (ELISAs) (Euroimmun anti-SARS-CoV-2 nucleocapsid protein [NCP] immunoglobulin G [IgG], Euroimmun spike SARS-CoV-2 IgG, Mologic Omega COVID-19 IgG, Bio-Rad Platelia SARS-CoV-2 Total Ab) and one chemiluminescent microparticle immunoassay (Abbott Architect SARS-CoV-2 IgG) were evaluated. We estimated the analytical performance characteristics using plasma from 100 SARS-CoV-2 PCR-positive patients from varied time points post-PCR confirmation and 100 prepandemic samples (50 HIV positive and 50 hepatitis B positive). The Bio-Rad assay failed the manufacturer-specified validation steps. The Euroimmun NCP, Euroimmun spike, and Mologic assays had sensitivities of 73.7%, 74.4%, and 76.9%, respectively, on samples taken 15 to 58?days after PCR confirmation and specificities of 97%, 100%, and 83.8%, respectively. The Abbott assay had 71.3% sensitivity and 100% specificity on the same panel. Parallel or serial algorithms combining two tests did not substantially improve the sensitivity or specificity. Our results showed lower sensitivity and, for one immunoassay, lower specificity compared to the manufacturers’ results and other reported validations. Seroprevalence estimates using these assays might need to be interpreted with caution in Nigeria and similar settings. These findings highlight the importance of in-country validations of SARS-CoV-2 serological assays prior to use to ensure that accurate results are available for public health decision-making to control the COVID-19 pandemic in Africa. IMPORTANCE This study used positive and negative sample panels from Nigeria to test the performance of several commercially available SARS-CoV-2 serological assays. Using these prepandemic and SARS-CoV-2-positive samples, we found much lower levels of sensitivity in four commercially available assays than most assay manufacturer reports and independent evaluations. The use of these assays with suboptimal sensitivity and specificity in Nigeria or countries with population exposure to similar endemic pathogens could lead to a biased estimate of the seroprevalence, over- or underestimating the true disease prevalence, and limit efforts to stop the spread of SARS-CoV-2. It is important to conduct in-country validations of serological SARS-CoV-2 assays prior to their widespread use, especially in countries with limited representation in published assay validations. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510257/ | 180 | 2165-0497 | Microbiology Spectrum | Washington, DC : ASM Press | |
| 18494 | 901 | 치료법 | Sample size | Term | sample size | abstract | None | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 29896 | 901 | 치료법 | widespread | Term | widespread | abstract | abnormality | 8821 | 10.1128/Spectrum.00680-21 | Validation of Commercial SARS-CoV-2 Immunoassays in a Nigerian Population | Fehintola Ige@@@Yohhei Hamada@@@Laura Steinhardt@@@Nnaemeka C. Iriemenam@@@Mabel Uwandu@@@Stacie Marta Greby@@@Maureen Aniedobe@@@Babatunde Lawal Salako@@@Molebogeng X. Rangaka@@@Ibrahim Abubakar@@@Rosemary Audu | 202110 | Research Article | PMC | ABSTRACT Validated assays are essential for reliable serosurveys; however, most SARS-CoV-2 immunoassays have been validated using specimens from China, Europe, or U.S. populations. We evaluated the performance of five commercial SARS-CoV-2 immunoassays to inform their use in serosurveys in Nigeria. Four semiquantitative enzyme-linked immunosorbent assays (ELISAs) (Euroimmun anti-SARS-CoV-2 nucleocapsid protein [NCP] immunoglobulin G [IgG], Euroimmun spike SARS-CoV-2 IgG, Mologic Omega COVID-19 IgG, Bio-Rad Platelia SARS-CoV-2 Total Ab) and one chemiluminescent microparticle immunoassay (Abbott Architect SARS-CoV-2 IgG) were evaluated. We estimated the analytical performance characteristics using plasma from 100 SARS-CoV-2 PCR-positive patients from varied time points post-PCR confirmation and 100 prepandemic samples (50 HIV positive and 50 hepatitis B positive). The Bio-Rad assay failed the manufacturer-specified validation steps. The Euroimmun NCP, Euroimmun spike, and Mologic assays had sensitivities of 73.7%, 74.4%, and 76.9%, respectively, on samples taken 15 to 58?days after PCR confirmation and specificities of 97%, 100%, and 83.8%, respectively. The Abbott assay had 71.3% sensitivity and 100% specificity on the same panel. Parallel or serial algorithms combining two tests did not substantially improve the sensitivity or specificity. Our results showed lower sensitivity and, for one immunoassay, lower specificity compared to the manufacturers’ results and other reported validations. Seroprevalence estimates using these assays might need to be interpreted with caution in Nigeria and similar settings. These findings highlight the importance of in-country validations of SARS-CoV-2 serological assays prior to use to ensure that accurate results are available for public health decision-making to control the COVID-19 pandemic in Africa. IMPORTANCE This study used positive and negative sample panels from Nigeria to test the performance of several commercially available SARS-CoV-2 serological assays. Using these prepandemic and SARS-CoV-2-positive samples, we found much lower levels of sensitivity in four commercially available assays than most assay manufacturer reports and independent evaluations. The use of these assays with suboptimal sensitivity and specificity in Nigeria or countries with population exposure to similar endemic pathogens could lead to a biased estimate of the seroprevalence, over- or underestimating the true disease prevalence, and limit efforts to stop the spread of SARS-CoV-2. It is important to conduct in-country validations of serological SARS-CoV-2 assays prior to their widespread use, especially in countries with limited representation in published assay validations. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510257/ | 180 | 2165-0497 | Microbiology Spectrum | Washington, DC : ASM Press | |
| 16797 | 901 | 치료법 | SARS-CoV-2 | Virus | sars-cov-2 | author | 제2형 중증급성호흡기증후군 코로나바이러스 | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 18495 | 901 | 치료법 | SARS CoV | Virus | SARS cov | abstract | None | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 16798 | 901 | 치료법 | SARS-COV-2 infection | Disease | sars-cov-2 infection | abstract | SARS-COV-2 감염 | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 18496 | 901 | 치료법 | SARS CoV-2 | Virus | sars cov-2 | abstract | 사스 코로나바이러스 2 | 6524 | 10.1371/journal.pone.0247767 | Evaluation of sample pooling for screening of SARS CoV-2 | Andargachew Mulu@@@Dawit Hailu Alemayehu@@@Fekadu Alemu@@@Dessalegn Abeje Tefera@@@Sinknesh Wolde@@@Gebeyehu Aseffa@@@Tamrayehu Seyoum@@@Meseret Habtamu@@@Alemseged Abdissa@@@Abebe Genetu Bayih@@@Getachew Tesfaye Beyene@@@Etsuro Ito@@@Etsuro Ito@@@Etsuro Ito | 202102 | Research Article | PMC | Background The coronavirus disease 2019 (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability, an efficient method is urgently needed. Objectives To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2. Methods We evaluated pooling approach on both direct clinical and NA samples. The standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 was employed targeting the nucleocapsid (N) and open reading frame (ORF1ab) genomic region of the virus. The experimental pools were created using SARS CoV-2 positive clinical samples and extracted RNA spiked with up to 9 negative samples. For the direct clinical samples viral NA was extracted from each pool to a final extraction volume of 200μL, and subsequently both samples tested using the SARS CoV-2 RT-PCR assay. Results We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the cycle threshold (Ct) value of the original sample, corresponding to high, and low SARS CoV-2 viral copies per reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend pooling of 4/5 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 5 in 1 was expected to retain accuracy of the test irrespective of the Ct value samples spiked, and result in a 137% increase in testing efficiency. Conclusions The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community. We recommend clinical sample pooling of 4 or 5 in 1. However, we don’t advise pooling of clinical samples when disease prevalence is greater than 7%; particularly when sample size is large. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909632/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 10413 | 901 | 치료법 | Replication | Action | replication | abstract | 복제 | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 10414 | 901 | 치료법 | replicon | Term | replicon | author,abstract | 레플리콘 | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 10416 | 901 | 치료법 | respiratory | Term | respiratory | abstract | 호흡기 | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 10417 | 901 | 치료법 | resulting | Action | resulting | abstract | None | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 10420 | 901 | 치료법 | SARS-CoV-2 biology | Term | sars-cov-2 biology | abstract | None | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 118797 | 901 | 치료법 | significantly | Action | significantly | abstract | None | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 10421 | 901 | 치료법 | SARS-CoV-2 protein | Protein | sars-cov-2 protein | abstract | None | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 16799 | 901 | 치료법 | SARS-CoV-2 PCR | Term | sars-cov-2 pcr | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 10422 | 901 | 치료법 | SARS-CoV-2 proteins | Protein | sars-cov-2 protein | abstract | None | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 118798 | 901 | 치료법 | significantly higher | Action | significantly higher | abstract | None | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 118799 | 901 | 치료법 | specific treatment | Treatment | specific treatment | abstract | None | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 10423 | 901 | 치료법 | SARS-CoV-2 virus | Virus | sars-cov-2 virus | abstract | SARS-COV-2 바이러스 | 2436 | 10.1128/JVI.00687-21 | Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies | Hai Trong Nguyen@@@Darryl Falzarano@@@Volker Gerdts@@@Qiang Liu | 202108 | Article | PMC | {{{ Abstract }}} !! The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, resulting in global public health emergencies and economic crises. In the present study, a noninfectious and biosafety level 2 (BSL2)-compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting nonstructural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, a U.S. Food and Drug Administration-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof of principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL2-compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In the present study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level 3 (BSL3) facility, the replicon is noninfectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology. !!{{ Keywords: }} SARS-CoV-2; antivirals; nano luciferase; nonstructural protein 15; nucleocapsid protein; replicon; reverse genetics. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387049/ | 81 | 0022-538X | Journal of Virology | Washington Dc : American Society For Microbiology. | |
| 118800 | 901 | 치료법 | steroid | Term | steroid | abstract | 스테로이드 | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 118801 | 901 | 치료법 | Steroids | Term | steroid | abstract | 스테로이드 | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 18117 | 901 | 치료법 | virus | Term | virus | abstract | 바이러스 | 6476 | 10.1371/journal.pone.0249069 | Low risk of SARS-CoV-2 in blood transfusion | Michael Owusu@@@Augustina Angelina Sylverken@@@Philip El-Duah@@@Nana Kwame Ayisi-Boateng@@@Richmond Yeboah@@@Eric Adu@@@Jesse Asamoah@@@Michael Frimpong@@@Japhet Senyo@@@Godfred Acheampong@@@Mohamed Mutocheluh@@@John Amuasi@@@Ellis Owusu-Dabo@@@Yaw Adu-Sarkodie@@@Richard Odame Phillips | 202104 | Research Article | PMC | Background The novel coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to remain a global challenge. There is emerging evidence of SARS-CoV-2 virus found in the blood of patients from China and some developed countries. However, there is inadequate data reported in Ghana and other parts of Africa, where blood transfusion service heavily relies on voluntary and replacement blood donors. This study aimed to investigate whether plasma of infected individuals could pose significant transfusion transmitted risk of COVID-19 in Ghanaian populations. Methods This cross-sectional retrospective study was conducted at the Kumasi Centre for Collaborative Research into Tropical Medicine (KCCR), KNUST, Ghana. Study subjects comprised contacts of COVID-19 individuals, those with classical symptoms of COVID-19 and individuals who had recovered based on the new Ghana discharge criteria. Whole blood, sputum or deep coughed saliva samples were collected and transported to KCCR for SARS-CoV-2 testing. Viral nucleic acid was extracted from sputum/nasopharyngeal samples using Da An Gene column based kit and from plasma using LBP nucleic acid extraction kit. Real-Time PCR was performed specifically targeting the ORF1ab and Nucleocapsid (N) genomic regions of the virus. Results A total of 97 individuals were recruited into the study, with more than half being males (58; 59.7%). The mean age of all subjects was 33 years (SD = 7.7) with minimum being 22 years and maximum 56 years. Majority (76; 78.4%) of all the subjects were asymptomatic, and among the few symptomatic subjects, cough (10; 10.3%) was the most predominant symptom. Of the 97 sputum samples tested, 79 (81.4%) were positive for SARS-CoV-2. We identified SARS-CoV-2 viral RNA in the plasma of 1 (1.03%) subject who had clinically recovered. Conclusion This study reports the identification of SARS-CoV-2 viral RNA in a convalescent individual in Ghana. Due to the low prevalence observed and the marginal cycling thresholds associated, the risk of transfusion transmission of SARS-CoV-2 is negligible. Well-powered studies and advanced diagnostics to determine infectious viremia is recommended to further evaluate the potential risk of hematogenous transmission among recovered patients. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043372/ | 49 | 1932-6203 | PLoS ONE | San Francisco, CA : Public Library of Science. | |
| 118802 | 901 | 치료법 | stroke | Disease | stroke | abstract | 발작 | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 118803 | 901 | 치료법 | therapeutic | Term | therapeutic | abstract | 치료적 | 35164 | 10.1182/blood-2020-137707 | Impact of Treatment and Anticoagulation on Thrombosis in COVID-19 Patients | Surbhi Warrior MDMPH@@@Elizabeth Behrens MD@@@Joshua Thomas MD@@@Priya Rajakumar MD@@@Sefer Gezer MD@@@Parameswaran Venugopal MD@@@Shivi Jain MDMBBS | 202102 | Conference abstract | Sciencedirect | Background!!The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19.!!Methods!!A retrospective analysis was performed on all COVID-19 patients hospitalized between March 2020 and June 2020 at our institution. Patient charts were individually reviewed to ensure accuracy of data. Thromboembolic events (VTE or ATE) verified by imaging were included in the analysis. The impact of COVID-19 specific treatments such as Remdesivir, Tocilizumab, Hydroxychloroquine, and steroids on incidence of thrombosis was analyzed by using X2 testing. Using logistics regression, we analyzed the effect of prophylactic versus therapeutic anticoagulation received before development of thrombosis on mortality.!!Results!!Out of 1265 COVID-19 positive hospitalized patients during our time frame, 138 (10.9%) had thromboembolism. Incidence of 6.3% VTE, 5.6% DVT, 4.8% PE in COVID-19 patients was significantly higher than 0.24% VTE, 0.15% DVT, 0.12% PE in non COVID-19 hospitalized patients as reported by CDC (p<.0001 for all). Amongst patients with COVID-19, mortality for patients with thrombosis is significantly higher than patients without thrombosis (31.9% vs. 10%, p<0.001). Hispanic patients had a significantly higher mortality rate of 51% compared to African American 18%, other 29%, or Caucasian 20% (p=0.0020). Patients with PE had a significantly higher mortality rate than patients with non-pulmonary thrombotic events (18.0% vs. 13.7%, p=0.0412).The incidence of thrombosis was significantly less in those who received steroids at 14% as compared to other COVID-19 treatment: Tocilizumab 25% (p=0.0031), Hydroxychloroquine 42% (p<.0001), and Remdesivir 72% (p<.0001). Adjusting for gender, age, race, BMI, the mortality rate in COVID-19 patients with thrombosis was higher in patients who had COVID-19 related treatment compared to without treatment: Remdesivir OR (4.67, 95% CI 1.43- 15.2), steroids OR (4.52, 95% CI 1.82- 11.18), Tocilizumab OR (2.51, 95% CI 1.06-5.96), and Hydroxychloroquine OR (1.54, 95% CI .661- 3.59). There was no difference in mortality in patients who had prophylactic enoxaparin 40.5% compared to therapeutic enoxaparin 51.7% (p= 0.3491) (Figure 1). Adjusting for all demographics, a logistics model showed βprophylaxis anticoagulation= βTherapeutic anticoagulation showing no mortality difference in patients who had either dosing of anticoagulation (difference=0.2658, Z=.55, p=0.5810).!!Conclusion!!In Our study the incidence of thrombosis in hospitalized COVID-19 patients was significantly higher than non-COVID-19 hospitalized patients. COVID-19 patients with thrombosis had higher mortality compared to COVID-19 patient without thrombosis, particularly patients with PE. Hispanic patients with COVID-19 and thrombosis experienced a higher mortality rate compared to non-Hispanic patients. The lowest incidence of thrombosis occurred in COVID-19 patients who received steroids, followed by Tocilizumab suggesting that steroids and Tocilizumab may reduce the pro-inflammatory state leading to thrombosis. However, mortality rate was higher in patients who received COVID-19 related treatment, suggesting that these patients likely had severe disease. There was no mortality difference in patients who received prophylactic versus therapeutic anticoagulation prior to thrombosis. Randomized control trials will address the impact of anticoagulation dosing on morbidity and mortality in COVID-19 patients and study the post discharge prophylaxis and long-term outcomes in these patients.!!Download : Download high-res image (130KB)Download : Download full-size image!!Disclosures!!No relevant conflicts of interest to declare. | https://doi.org/10.1182/blood-2020-137707 | 1048 | 0006-4971 | Blood | [New York] : Elsevier. | |
| 69691 | 901 | 치료법 | coronavirus disease | Disease | coronavirus disease | abstract | 코로나바이러스 질환 | 15721 | 10.1080/07391102.2020.1778536 | Virtual screening and dynamics of potential inhibitors targeting RNA binding domain of nucleocapsid phosphoprotein from SARS-CoV-2 | Rohitash Yadav@@@Mohammed Imran@@@Puneet Dhamija@@@Kapil Suchal@@@Shailendra Handu | 202108 | Article | PMC | {{{ Abstract }}} !! The emergence of the coronavirus disease-2019 pandemic has led to an outbreak in the world. The SARS-CoV-2 is seventh and latest in coronavirus family with unique exonucleases for repairing any mismatches in newly transcribed genetic material. Therefore, drugs with novel additional mechanisms are required to simultaneously target and eliminate the virus. Thus, a newly deciphered N protein is taken as a target that belongs to SARS-CoV-2. They play a vital role in RNA transcription, viral replication and new virion formation. This study used virtual screening, molecular modeling and docking of the 8987 ligands from Asinex and PubChem databases against this novel target protein. Three hotspot sites having DScore ≥1 (Site 1, Site 2 and Site 3) for ligand binding were selected. Subsequently, high throughput screening, standard precision and extra precision docking process and molecular dynamics concluded three best drugs from two libraries. Two antiviral moieties from Asinex databases (5817 and 6799) have docking scores of -10.29 and -10.156; along with their respective free binding energies (Δ G bind) of -51.96 and -64.36 on Site 3. The third drug, Zidovudine, is from PubChem database with docking scores of -9.75 with its binding free energies (Δ G bind) of -59.43 on Site 3. The RMSD and RMSF were calculated for all the three drugs through molecular dynamics simulation studies for 50 ns. Zidovudine shows a very stable interaction with fluctuation starting at 2.4 ? on 2 ns and remained stable at 3 ? from 13 to 50 ns. Thus, paving the way for further biological validation as a potential treatment.Communicated by Ramaswamy H. Sarma. !!{{ Keywords: }} COVID-19; SARS-CoV-2; docking; molecular dynamics; nucleocapsid phosphoprotein. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332875/ | 219 | 0739-1102 | Journal of biomolecular structure & dynamics | June 2012- : Oxon, UK : Taylor & Francis. | |
| 79637 | 901 | 치료법 | enzyme | Enzyme | enzyme | abstract | None | 15973 | 10.1016/j.mehy.2020.110468 | The plausible mechanisms of tramadol for treatment of COVID-19 | Nahla E El-Ashmawy@@@Abdel-Halim A Lashin@@@Kamal M Okasha@@@Amal M Abo Kamer@@@Tarek M Mostafa@@@Mona El-Aasr@@@Ahmed E Goda@@@Yusuf A Haggag@@@Haytham O Tawfik@@@Mariam A Abo-Saif | 202101 | Review | PMC | {{{ Abstract }}} !! Currently, no single medication has been approved for the management of coronavirus disease-2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, drug repositioningby investigating the use of existing drugs for management of COVID-19 patients is considered a desperate need. Tramadol is a commonly prescribed analgesic drug for treatment of moderate to severe pain with less potential for dependence and respiratory depression. Multiple evidence support that tramadol is a promising drug for treatment of COVID-19 patients. Herein, we discuss the possible beneficial effects of using tramadol against SARS-CoV-2 infection and their underlying mechanism of action. The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Besides, tramadol activates natural killer (NK) and T-cells and enhances IL-2 secretion, which produce immune-enhancing effect against SARS-CoV-2. Recent studies confirmed that COVID-19 patients with acute respiratory failure showed increased fibrin formation and polymerization that may lead to thrombosis. Tramadol owing to its hypocoagulable effect may protect against venous thromboembolism in these patients. Moreover, tramadol can exert a cardioprotective effect via decreasing lactate dehydrogenase (LDH) level which is elevated in most of patients with COVID-19. Furthermore, the severity and mortality of COVID-19 have been correlated with old age patients, which may be due to the lack of antioxidant mechanisms and increased oxidative damage. Tramadol could protect COVID-19 patient from disease complications by increases the antioxidant enzymes superoxide dismutase and glutathione peroxidase while diminished malondialdehyde. More interestingly, tramadol as an effective analgesic and antitussive may have a beneficial effect on COVID-19 patients suffering from cough, headache, ache, and pain. The tramadol anti-psychotic effect may also protect against psychiatric disorders associated with SARS-CoV-2 infection. Moreover, tramadol has bactericidal activity against a wide range of pathogens including Pseudomonas aeruginosa which is common in severe COVID-19 patients leading to pneumonia with worse clinical outcomes. Therefore, we hypothesize that tramadol might be a promising adjuvant therapeutic option against SARS-CoV-2 infection. Based on that, tramadol should be considered as adjuvant therapy for COVID-19 clinical trials. !!{{ Keywords: }} Anti-inflammatory; COVID-19; Hypocoagulable effect; Immune-enhancing; SARS-CoV-2; Tramadol. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831961/ | 2493 | 0306-9877 | Medical Hypotheses | Penrith, Eng., Eden Press. | |
| 79638 | 901 | 치료법 | Evidence | Term | evidence | abstract | None | 15973 | 10.1016/j.mehy.2020.110468 | The plausible mechanisms of tramadol for treatment of COVID-19 | Nahla E El-Ashmawy@@@Abdel-Halim A Lashin@@@Kamal M Okasha@@@Amal M Abo Kamer@@@Tarek M Mostafa@@@Mona El-Aasr@@@Ahmed E Goda@@@Yusuf A Haggag@@@Haytham O Tawfik@@@Mariam A Abo-Saif | 202101 | Review | PMC | {{{ Abstract }}} !! Currently, no single medication has been approved for the management of coronavirus disease-2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, drug repositioningby investigating the use of existing drugs for management of COVID-19 patients is considered a desperate need. Tramadol is a commonly prescribed analgesic drug for treatment of moderate to severe pain with less potential for dependence and respiratory depression. Multiple evidence support that tramadol is a promising drug for treatment of COVID-19 patients. Herein, we discuss the possible beneficial effects of using tramadol against SARS-CoV-2 infection and their underlying mechanism of action. The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Besides, tramadol activates natural killer (NK) and T-cells and enhances IL-2 secretion, which produce immune-enhancing effect against SARS-CoV-2. Recent studies confirmed that COVID-19 patients with acute respiratory failure showed increased fibrin formation and polymerization that may lead to thrombosis. Tramadol owing to its hypocoagulable effect may protect against venous thromboembolism in these patients. Moreover, tramadol can exert a cardioprotective effect via decreasing lactate dehydrogenase (LDH) level which is elevated in most of patients with COVID-19. Furthermore, the severity and mortality of COVID-19 have been correlated with old age patients, which may be due to the lack of antioxidant mechanisms and increased oxidative damage. Tramadol could protect COVID-19 patient from disease complications by increases the antioxidant enzymes superoxide dismutase and glutathione peroxidase while diminished malondialdehyde. More interestingly, tramadol as an effective analgesic and antitussive may have a beneficial effect on COVID-19 patients suffering from cough, headache, ache, and pain. The tramadol anti-psychotic effect may also protect against psychiatric disorders associated with SARS-CoV-2 infection. Moreover, tramadol has bactericidal activity against a wide range of pathogens including Pseudomonas aeruginosa which is common in severe COVID-19 patients leading to pneumonia with worse clinical outcomes. Therefore, we hypothesize that tramadol might be a promising adjuvant therapeutic option against SARS-CoV-2 infection. Based on that, tramadol should be considered as adjuvant therapy for COVID-19 clinical trials. !!{{ Keywords: }} Anti-inflammatory; COVID-19; Hypocoagulable effect; Immune-enhancing; SARS-CoV-2; Tramadol. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831961/ | 2493 | 0306-9877 | Medical Hypotheses | Penrith, Eng., Eden Press. | |
| 16800 | 901 | 치료법 | second dose | Term | second dose | abstract | None | 5963 | 10.1186/s12879-022-07083-1 | Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine | Andrea Lombardi@@@Giulia Renisi@@@Dario Consonni@@@Massimo Oggioni@@@Patrizia Bono@@@Sara Uceda Renteria@@@Alessandra Piatti@@@Angela Cecilia Pesatori@@@Silvana Castaldi@@@Antonio Muscatello@@@Luciano Riboldi@@@Ferruccio Ceriotti@@@Andrea Gori@@@Alessandra Bandera | 202201 | Research | PMC | Background The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. Methods Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and?who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March?April 2021. Results Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4?years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2?days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2?days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55?days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. Conclusions Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795942/ | 2 | 1471-2334 | BMC Infectious Diseases | London : BioMed Central | |
| 29866 | 901 | 치료법 | nucleocapsid protein | Protein | nucleocapsid protein | abstract | 뉴클레오캡시드 단백질 | 8821 | 10.1128/Spectrum.00680-21 | Validation of Commercial SARS-CoV-2 Immunoassays in a Nigerian Population | Fehintola Ige@@@Yohhei Hamada@@@Laura Steinhardt@@@Nnaemeka C. Iriemenam@@@Mabel Uwandu@@@Stacie Marta Greby@@@Maureen Aniedobe@@@Babatunde Lawal Salako@@@Molebogeng X. Rangaka@@@Ibrahim Abubakar@@@Rosemary Audu | 202110 | Research Article | PMC | ABSTRACT Validated assays are essential for reliable serosurveys; however, most SARS-CoV-2 immunoassays have been validated using specimens from China, Europe, or U.S. populations. We evaluated the performance of five commercial SARS-CoV-2 immunoassays to inform their use in serosurveys in Nigeria. Four semiquantitative enzyme-linked immunosorbent assays (ELISAs) (Euroimmun anti-SARS-CoV-2 nucleocapsid protein [NCP] immunoglobulin G [IgG], Euroimmun spike SARS-CoV-2 IgG, Mologic Omega COVID-19 IgG, Bio-Rad Platelia SARS-CoV-2 Total Ab) and one chemiluminescent microparticle immunoassay (Abbott Architect SARS-CoV-2 IgG) were evaluated. We estimated the analytical performance characteristics using plasma from 100 SARS-CoV-2 PCR-positive patients from varied time points post-PCR confirmation and 100 prepandemic samples (50 HIV positive and 50 hepatitis B positive). The Bio-Rad assay failed the manufacturer-specified validation steps. The Euroimmun NCP, Euroimmun spike, and Mologic assays had sensitivities of 73.7%, 74.4%, and 76.9%, respectively, on samples taken 15 to 58?days after PCR confirmation and specificities of 97%, 100%, and 83.8%, respectively. The Abbott assay had 71.3% sensitivity and 100% specificity on the same panel. Parallel or serial algorithms combining two tests did not substantially improve the sensitivity or specificity. Our results showed lower sensitivity and, for one immunoassay, lower specificity compared to the manufacturers’ results and other reported validations. Seroprevalence estimates using these assays might need to be interpreted with caution in Nigeria and similar settings. These findings highlight the importance of in-country validations of SARS-CoV-2 serological assays prior to use to ensure that accurate results are available for public health decision-making to control the COVID-19 pandemic in Africa. IMPORTANCE This study used positive and negative sample panels from Nigeria to test the performance of several commercially available SARS-CoV-2 serological assays. Using these prepandemic and SARS-CoV-2-positive samples, we found much lower levels of sensitivity in four commercially available assays than most assay manufacturer reports and independent evaluations. The use of these assays with suboptimal sensitivity and specificity in Nigeria or countries with population exposure to similar endemic pathogens could lead to a biased estimate of the seroprevalence, over- or underestimating the true disease prevalence, and limit efforts to stop the spread of SARS-CoV-2. It is important to conduct in-country validations of serological SARS-CoV-2 assays prior to their widespread use, especially in countries with limited representation in published assay validations. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510257/ | 180 | 2165-0497 | Microbiology Spectrum | Washington, DC : ASM Press |
| 판매제공처 홈페이지 | 판매담당자 | 연락처 | 이메일 |
|---|---|---|---|
| www.vinea.co.kr | (주)비네아 | 010-8703-2109 | bongbong@vinea.co.kr |
| 상품명 | 가격 |
|---|---|
| COVID19 데이터셋 | 3000000 |
| 진단 데이터셋 공개데이터 | 0 |
| 신종인플루엔자 데이터셋 | 2000000 |
| 홍역 데이터셋 | 3000000 |
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| 데이터 상품은 디지털화된 상품의 특성상 반품, 취소, 환불 되지 않으나 데이터의 심각한 오류, 상이한 데이터에 한하여 구매자가 요구하는 경우 환불을 진행할 수 있습니다. |