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 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. Findings 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 to 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. Interpretation RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond ten 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.

SARS-CoV-2 RNA and antibody dynamics in a Dutch household study with dense sampling frame

“…For SARS-CoV-2 diagnostics late in infection or in past infections, RT-PCR on feces and oral fluid specimens are more valuable than NP and OP specimens, since the presence of viral RNA in especially feces remain present over a longer time compared to NP and OP swab specimens. This is in line with findings of other studies that indicate that SARS-CoV-2 RNA can be detected up to 126 days in feces compared to 83 days in respiratory specimens and that beyond 10 dps, feces sampling may be preferred [22,24,25]. Although SARS-CoV-2 RNA can remain present in respiratory and feces specimens for a long time, the duration of presence of viable virus is relatively short-lived [26,27].…”

Diagnostic accuracy of point-of-care tests in acute community-acquired lower respiratory tract infections. A systematic review and meta-analysis

“…More methodologically rigorous studies conducted at different community settings and in LMICs may contribute to better define LUS's potential at POC. Molecular tests were confirmed as the most accurate pathogen-based diagnostic tests currently available, with considerably higher accuracy compared with the other pathogen-based tests, despite several factors that could have been negatively affecting the results, as the timing of sampling -both since the infection and the onset of symptoms -and the location of the sampling (38). Nonetheless, the applicability of molecular tests at POC is limited due to the need for laboratory infrastructure, expensive equipment, skilled personnel and prolonged turn-around times.…”

Setting minimum clinical performance specifications for tests based on disease prevalence and minimum acceptable positive and negative predictive values: Practical considerations applied to COVID-19 testing

“…Most NAATs and serology tests for COVID-19 performed on the modern generation of analyzers claim clinical specificity of ≥95%, but with varying clinical sensitivity [16] . However, given high risk of bias in most diagnostic accuracy studies published to date, a range of clinical specificity beyond those claimed by the manufacturer should be allowed for when setting the minimum required clinical sensitivity [17] , [18] .…”

“…This may open the possibility of selecting tests characterized by rapid turnaround time but having lower clinical sensitivity 19 or using combination testing. Importantly, the clinical performance of a test may change dynamically throughout the course of the infection [18] , [19] , [20] , [21] . Practitioners should therefore apply the test within the time window where the clinical sensitivity is highest to optimize the desired post-test probability.…”