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Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure.
Ann Intern Med. 2020 08 18; 173(4):262-267.AIM

Abstract

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.

Links

PMC Free PDF

Authors+Show Affiliations

Kucirka LM
Johns Hopkins School of Medicine, Baltimore, Maryland (L.M.K.).
Lauer SA
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (S.A.L., D.B., J.L.).
Laeyendecker O
Johns Hopkins School of Medicine, Johns Hopkins Bloomberg School of Public Health, and National Institute of Allergy and Infectious Diseases, Baltimore, Maryland (O.L.).
Boon D
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (S.A.L., D.B., J.L.).
Lessler J
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (S.A.L., D.B., J.L.).

MeSH

Bayes TheoremBetacoronavirusCOVID-19Coronavirus InfectionsFalse Negative ReactionsHumansPandemicsPneumonia, ViralReproducibility of ResultsReverse Transcriptase Polymerase Chain ReactionRisk FactorsSARS-CoV-2

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Review

Language

eng

PubMed ID

32422057

Clinical Trial Links

Evaluation of the AudibleHealth Dx AI/ML-Based Dx SaMD Using FCV-SDS in the Diagnosis of COVID-19 Illness: Clinical Validation
A Clinical Evaluation of COVID-19 Rapid Point of Care Antigen Tests
Evaluation of the AudibleHealth Dx AI/ML-Based Dx SaMD Using FCV-SDS in the Diagnosis of COVID-19 Illness
Wearable Diagnostic for Detection of COVID-19 Infection

Citation

Kucirka, Lauren M., et al. "Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests By Time Since Exposure." Annals of Internal Medicine, vol. 173, no. 4, 2020, pp. 262-267.
Kucirka LM, Lauer SA, Laeyendecker O, et al. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Ann Intern Med. 2020;173(4):262-267.
Kucirka, L. M., Lauer, S. A., Laeyendecker, O., Boon, D., & Lessler, J. (2020). Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Annals of Internal Medicine, 173(4), 262-267. https://doi.org/10.7326/M20-1495
Kucirka LM, et al. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests By Time Since Exposure. Ann Intern Med. 2020 08 18;173(4):262-267. PubMed PMID: 32422057.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. AU - Kucirka,Lauren M, AU - Lauer,Stephen A, AU - Laeyendecker,Oliver, AU - Boon,Denali, AU - Lessler,Justin, Y1 - 2020/05/13/ PY - 2020/5/19/pubmed PY - 2020/8/28/medline PY - 2020/5/19/entrez SP - 262 EP - 267 JF - Annals of internal medicine JO - Ann Intern Med VL - 173 IS - 4 N2 - 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. SN - 1539-3704 UR - https://www.unboundmedicine.com/medline/citation/32422057/full_citation DB - PRIME DP - Unbound Medicine ER -