Abstract

BackgroundReverse-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.AimTo determine how the probability of obtaining a false-negative test in infected patients is affected by time since symptom onset and swab type.MethodsWe 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.ResultsThe 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.ConclusionNP 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.

Highlights

  • Most SARS-CoV-2 infected individuals are identified by successful amplification of the virus from nasopharyngeal or oropharyngeal swabs using a reverse-transcription PCR (RT-PCR) assay

  • Liu et al [8] and Zhao et al [7] demonstrated that the proportion of positive tests among infected patients reduced with each week after symptom onset, and Luo et al [11] reported that the initial sensitivity of oropharyngeal swabs in secondary contacts was 71%

  • Days since symptom onset GAMM: generalised additive mixed models; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2. a Data were obtained from published studies on patients from China, United States, France and Singapore

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Summary

Introduction

Most SARS-CoV-2 infected individuals are identified by successful amplification of the virus from nasopharyngeal or oropharyngeal swabs using a reverse-transcription PCR (RT-PCR) assay. These tests are highly specific but there are many reasons why sensitivity is imperfect [1]. Fang et al [3] found that RT-PCR was only able to identify 36/51 (71%) of SARS-CoV-2 infected patients when using swabs taken 0–6 days after 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. This has implications for identifying infected patients, contact tracing and discharging convalescing patients who are potentially still infectious

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