False-Negative Rate of RT-PCR SARS-CoV-2 Tests
- Tests for SARS-CoV-2 based on RT-PCR add little diagnostic value in the first 5 days immediately after exposure.
- Decisions regarding removing contact precautions or ending quarantine should not be made on the basis of results obtained in the first 5 days post-exposure and absence of symptoms.
- Serial testing may improve test performance but needs to be studied..
What is the false-negative rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing using reverse transcriptase polymerase chain reaction (RT-PCR) according to time from exposure?
In this pooled analysis, the authors pooled data from seven previously published studies (two preprints and five peer-reviewed articles, total n = 1,330) providing results on RT-PCR testing for SARS-CoV-2 and time since onset of symptoms or exposure. Only confirmed cases and studies in which samples were collected from the upper respiratory tract (nasopharyngeal and oropharyngeal) were included. A Bayesian hierarchical model was fitted to estimate the false-negative rate by day since exposure and symptom onset. The model assumed a specificity of 100% for the RT-PCR, and a 5-day incubation period for the virus.
Over the 4 days of infection before the typical time of symptom onset (day 5), the probability of a false-negative result in an infected person decreased from 100% (95% confidence interval [CI], 100%-100%) on day 1 to 67% (CI, 27%-94%) on day 4. On the day of symptom onset, the median false-negative rate was 38% (CI, 18%-65%). This decreased to 20% (CI, 12%-30%) on day 8 (3 days after symptom onset) then began to increase again, from 21% (CI, 13%-31%) on day 9 to 66% (CI, 54%-77%) on day 21. The false-negative rate was minimized 8 days after exposure—that is, 3 days after the onset of symptoms on average.
The false-negative rate for SARS-CoV-2 RT-PCR testing is highly variable: highest within the first 5 days after exposure (up to 67%), and lowest on day 8 after exposure (21%).
Based on this analysis, the false-negative rate for SARS-CoV-2 RT-PCR is shockingly high, even at its lowest on day 8 post-exposure, or 3 days after symptoms. At its best, one out of five people suspected of COVID-19 will test negative. If clinical suspicion is high, infection should not be ruled out on the basis of RT-PCR alone. Given the importance of testing for both individual and public health and for guiding policy, the high variability and poor performance of the test should give pause to both healthcare providers and policymakers alike. Major initiatives by the National Institutes of Health and industry are underway to accelerate the development and availability of new diagnostic tests for COVID-19.
Keywords: Coronavirus, COVID-19, Diagnostic Tests, Routine, False Negative Reactions, Primary Prevention, Public Health, Reverse Transcriptase Polymerase Chain Reaction, SARS Virus, severe acute respiratory syndrome coronavirus 2
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