Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure

By L. Kucirka, S. Lauer, O. Laeyendecker, D. Boon, Justin Lessler. Annals of Internal Medicine, 2020

1,300 citations recorded by the source corpus.

Background: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse transcriptase polymerase chain reaction (RT-PCR) are being used to “rule out” infection among high-risk persons, such as exposed inpatients and health care workers. It is critical to understand how the predictive value of the test varies with time from exposure and symptom onset to avoid being falsely reassured by negative test results. Objective: To estimate the false-negative rate by day since infection. Design: Literature review and pooled analysis. Setting: 7 previously published studies providing data on RT-PCR performance by time since symptom onset or SARS-CoV-2 exposure using samples from the upper respiratory tract (n = 1330). Patients: A mix of inpatients and outpatients with SARS-CoV-2 infection. Measurements: A Bayesian hierarchical model was fitted to estimate the false-negative rate by day since exposure and symptom onset. Results: 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 decreases from 100% (95% CI, 100% to 100%) on day 1 to 67% (CI, 27% to 94%) on day 4. On the day of symptom onset, the median false-negative rate was 38% (CI, 18% to 65%). This decreased to 20% (CI, 12% to 30%) on day 8 (3 days after symptom onset) then began to increase again, from 21% (CI, 13% to 31%) on day 9 to 66% (CI, 54% to 77%) on day 21. Limitation: Imprecise estimates due to heterogeneity in the design of studies on which results were based. Conclusion: Care must be taken in interpreting RT-PCR tests for SARS-CoV-2 infection—particularly early in the course of infection—when using these results as a basis for removing precautions intended to prevent onward transmission. If clinical suspicion is high, infection should not be ruled out on the basis of RT-PCR alone, and the clinical and epidemiologic situation should be carefully considered. Primary Funding Source: National Institute of Allergy and Infectious Diseases, Johns Hopkins Health System, and U.S. Centers for Disease Control and Prevention.

Subfields: Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/121370fcecf53173fa237e0607a84d0058bed85a

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Citations in the corpus

Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients (2020, positive): “RT-PCR based detection of SARS-CoV-2 is sensitive early in the first week after the onset of symptoms (13), and our results suggest that the detection of antibodies against the SARS-CoV-2 RBD by ELISA, even when utilizing all isotypes, is not likely to contribute significantly to the early…”
Characterizing long COVID in an international cohort: 7 months of symptoms and their impact (2020, background): “Furthermore, the likelihood of false negatives increases after day 3 of symptom onset, when the false negative rate is 20%, reaching 66% by day 21[40].”