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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

Journal

BMC MEDICINE
Volume 18, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12916-020-01810-8

Keywords

SARS-CoV-2; RT-PCR; COVID-19; QUADAS-2; Diagnostic test; Anatomical sampling; IPD; Duration virus detection; Systematic review

Funding

  1. National Institute for Health Research (NIHR)
  2. UCL/UCLH Biomedical Research Centre
  3. NIHR Newcastle In Vitro Diagnostics Co-operative
  4. NIHR Leeds In Vitro Diagnostic Co-operative
  5. National Institute for Health Research (NIHR) Community Healthcare MedTech and In Vitro Diagnostics Co-operative at Oxford Health NHS Foundation Trust

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BackgroundTests 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.MethodsWe 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.ResultsOf 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from -6 to 66days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14days. 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 46days post-symptom onset.ConclusionsRT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10days 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.

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