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

• Published in: BMC medicine Vol. 18; no. 1; p. 346
• Main Authors: Mallett, Sue, 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04-11-2020; BioMed Central; BMC
• Subjects: Accuracy; Analysis; Anatomical sampling; Betacoronavirus - genetics; Betacoronavirus - isolation & purification; Bias; Clinical Laboratory Techniques; Confidence intervals; Coronaviridae; Coronavirus Infections - diagnosis; Coronavirus Infections - genetics; Coronaviruses; Correlation analysis; COVID-19; COVID-19 diagnostic tests; COVID-19 Testing; Data analysis; Diagnosis; Diagnostic test; DNA-directed RNA polymerase; Genetic aspects; Hospitals; Humans; Identification and classification; Infections; Infectivity; Longitudinal Studies; Medical diagnosis; Pandemics; Pneumonia, Viral - diagnosis; Pneumonia, Viral - genetics; Polymerase chain reaction; QUADAS-2; Respiratory diseases; Respiratory tract; Reverse Transcriptase Polymerase Chain Reaction - methods; Reverse Transcriptase Polymerase Chain Reaction - standards; Reverse transcription; Ribonucleic acid; Risk assessment; RNA; RT-PCR; Sampling; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Systematic review; Viral diseases; Viral load; Viruses; United Kingdom; COVID-19; Diagnostic test; SARS-CoV-2; QUADAS-2; RT-PCR; Anatomical sampling; Duration virus detection; Systematic review; IPD
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-020-01810-8

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.
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.
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.
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.