Estimating the false-negative test probability of SARS-CoV-2 by RT-PCR

BACKGROUND: Reverse-transcription PCR (RT-PCR) assays are used to test for infection with the SARS-CoV-2 virus. RT-PCR tests are highly specific and the probability of false positives is low, but false negatives are possible depending on swab type and time since symptom onset. AIM: To determine how the probability of obtaining a false-negative test in infected patients is affected by time since symptom onset and swab type. METHODS: We used generalised additive mixed models to analyse publicly available data from patients who received multiple RT-PCR tests and were identified as SARS-CoV-2 positive at least once. RESULTS: The probability of a positive test decreased with time since symptom onset, with oropharyngeal (OP) samples less likely to yield a positive result than nasopharyngeal (NP) samples. The probability of incorrectly identifying an uninfected individual due to a false-negative test was considerably reduced if negative tests were repeated 24 hours later. For a small false-positive test probability (<0.5%), the true number of infected individuals was larger than the number of positive tests. For a higher false-positive test probability, the true number of infected individuals was smaller than the number of positive tests. CONCLUSION: NP samples are more sensitive than OP samples. The later an infected individual is tested after symptom onset, the less likely they are to test positive. This has implications for identifying infected patients, contact tracing and discharging convalescing patients who are potentially still infectious.