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

Author:

Mallett SueORCID,Allen A. Joy,Graziadio Sara,Taylor Stuart A.,Sakai Naomi S.,Green Kile,Suklan Jana,Hyde Chris,Shinkins Bethany,Zhelev Zhivko,Peters Jaime,Turner Philip J.,Roberts Nia W.,di Ruffano Lavinia Ferrante,Wolff Robert,Whiting Penny,Winter Amanda,Bhatnagar Gauraang,Nicholson Brian D.,Halligan Steve

Abstract

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.

Funder

National Institute of Health Research

UCL/UCLH Biomedical Research Centre

NIHR senior investigator

NIHR Newcastle In Vitro Diagnostics Co-operative

NIHR Leeds In Vitro Diagnostic Co-operative

National Institute for Health Research (NIHR) Community Healthcare MedTech and In Vitro Diagnostics Co-operative at Oxford Health NHS Foundation Trust.

NIHR Academic Clinical Lecturer

National Institute for Health Research

Publisher

Springer Science and Business Media LLC

Subject

General Medicine

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