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
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
Affiliations
Sue Mallett
Centre for Medical Imaging, University College London
A. Joy Allen
NIHR In Vitro Diagnostics Co-operative, Newcastle University
Sara Graziadio
NIHR In Vitro Diagnostics Co-operative, Newcastle upon Tyne Hospitals NHS Foundation Trust
Stuart A. Taylor
Centre for Medical Imaging, University College London
Naomi S. Sakai
Centre for Medical Imaging, University College London
Kile Green
NIHR In Vitro Diagnostics Co-operative, Newcastle University
Jana Suklan
NIHR In Vitro Diagnostics Co-operative, Newcastle University
Chris Hyde
Exeter Test Group, Institute of Health Research, University of Exeter Medical School, University of Exeter
Bethany Shinkins
Test Evaluation Group, Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds
Zhivko Zhelev
Exeter Test Group, Institute of Health Research, University of Exeter Medical School, University of Exeter
Jaime Peters
Exeter Test Group, Institute of Health Research, University of Exeter Medical School, University of Exeter
Philip J. Turner
Nuffield Department of Primary Care Health Sciences, University of Oxford
Nia W. Roberts
Cancer Services, Gastroenterology, Population Health & Primary Care, Bodleian Health Care Libraries, University of Oxford
Lavinia Ferrante di Ruffano
Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham
Robert Wolff
Kleijnen Systematic Reviews Ltd
Penny Whiting
Bristol Medical School, University of Bristol
Amanda Winter
NIHR In Vitro Diagnostics Co-operative, Newcastle upon Tyne Hospitals NHS Foundation Trust
Gauraang Bhatnagar
Frimley Health NHS Foundation Trust
Brian D. Nicholson
Nuffield Department of Primary Care Health Sciences, University of Oxford
Steve Halligan
Centre for Medical Imaging, University College London
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.
