At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data
Abstract Background Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential...
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doaj-f3014ca9f7814ab8b99e56eedf96d1842020-11-25T04:05:57ZengBMCBMC Medicine1741-70152020-11-0118111710.1186/s12916-020-01810-8At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant dataSue Mallett0A. Joy Allen1Sara Graziadio2Stuart A. Taylor3Naomi S. Sakai4Kile Green5Jana Suklan6Chris Hyde7Bethany Shinkins8Zhivko Zhelev9Jaime Peters10Philip J. Turner11Nia W. Roberts12Lavinia Ferrante di Ruffano13Robert Wolff14Penny Whiting15Amanda Winter16Gauraang Bhatnagar17Brian D. Nicholson18Steve Halligan19Centre for Medical Imaging, University College LondonNIHR In Vitro Diagnostics Co-operative, Newcastle UniversityNIHR In Vitro Diagnostics Co-operative, Newcastle upon Tyne Hospitals NHS Foundation TrustCentre for Medical Imaging, University College LondonCentre for Medical Imaging, University College LondonNIHR In Vitro Diagnostics Co-operative, Newcastle UniversityNIHR In Vitro Diagnostics Co-operative, Newcastle UniversityExeter Test Group, Institute of Health Research, University of Exeter Medical School, University of ExeterTest Evaluation Group, Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of LeedsExeter Test Group, Institute of Health Research, University of Exeter Medical School, University of ExeterExeter Test Group, Institute of Health Research, University of Exeter Medical School, University of ExeterNuffield Department of Primary Care Health Sciences, University of OxfordCancer Services, Gastroenterology, Population Health & Primary Care, Bodleian Health Care Libraries, University of OxfordTest Evaluation Research Group, Institute of Applied Health Research, University of BirminghamKleijnen Systematic Reviews LtdBristol Medical School, University of BristolNIHR In Vitro Diagnostics Co-operative, Newcastle upon Tyne Hospitals NHS Foundation TrustFrimley Health NHS Foundation TrustNuffield Department of Primary Care Health Sciences, University of OxfordCentre for Medical Imaging, University College LondonAbstract Background Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. Methods We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. Results Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from − 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. Conclusions RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated.http://link.springer.com/article/10.1186/s12916-020-01810-8SARS-CoV-2RT-PCRCOVID-19QUADAS-2Diagnostic testAnatomical sampling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sue Mallett A. Joy Allen Sara Graziadio Stuart A. Taylor Naomi S. Sakai Kile Green Jana Suklan Chris Hyde Bethany Shinkins Zhivko Zhelev Jaime Peters Philip J. Turner Nia W. Roberts Lavinia Ferrante di Ruffano Robert Wolff Penny Whiting Amanda Winter Gauraang Bhatnagar Brian D. Nicholson Steve Halligan |
spellingShingle |
Sue Mallett A. Joy Allen Sara Graziadio Stuart A. Taylor Naomi S. Sakai Kile Green Jana Suklan Chris Hyde Bethany Shinkins Zhivko Zhelev Jaime Peters Philip J. Turner Nia W. Roberts Lavinia Ferrante di Ruffano Robert Wolff Penny Whiting Amanda Winter Gauraang Bhatnagar Brian D. Nicholson Steve Halligan At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data BMC Medicine SARS-CoV-2 RT-PCR COVID-19 QUADAS-2 Diagnostic test Anatomical sampling |
author_facet |
Sue Mallett A. Joy Allen Sara Graziadio Stuart A. Taylor Naomi S. Sakai Kile Green Jana Suklan Chris Hyde Bethany Shinkins Zhivko Zhelev Jaime Peters Philip J. Turner Nia W. Roberts Lavinia Ferrante di Ruffano Robert Wolff Penny Whiting Amanda Winter Gauraang Bhatnagar Brian D. Nicholson Steve Halligan |
author_sort |
Sue Mallett |
title |
At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data |
title_short |
At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data |
title_full |
At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data |
title_fullStr |
At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data |
title_full_unstemmed |
At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data |
title_sort |
at what times during infection is sars-cov-2 detectable and no longer detectable using rt-pcr-based tests? a systematic review of individual participant data |
publisher |
BMC |
series |
BMC Medicine |
issn |
1741-7015 |
publishDate |
2020-11-01 |
description |
Abstract Background Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. Methods We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. Results Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from − 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. Conclusions RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated. |
topic |
SARS-CoV-2 RT-PCR COVID-19 QUADAS-2 Diagnostic test Anatomical sampling |
url |
http://link.springer.com/article/10.1186/s12916-020-01810-8 |
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