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.
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Author, Article and Disclosure Information
Financial Support: In part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; by the Johns Hopkins Health System; by grant NU2GGH002000 from the U.S. Centers for Disease Control and Prevention; and by extramural grants R01AI135115 and T32DA007292 from the National Institutes of Health.
Disclosures: Dr. Lauer reports grants from the Centers for Disease Control and Prevention and National Institute of Allergy and Infectious Diseases during the conduct of the study. Dr. Laeyendecker reports salary from the National Institute of Allergy and Infectious Diseases Division of Intramural Research during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-1495.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Eliseo Guallar, MD, MPH, DrPH, Deputy Editor, Statistics, reports that he has no financial relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement: Study protocol: Further details are available from Dr. Kucirka (e-mail, [email protected]
Corresponding Author: Lauren M. Kucirka, MD, PhD, 600 North Wolfe Street, Phipps Building Suite 279, Baltimore, MD 21287; e-mail, [email protected]
Current Author Addresses: Dr. Kucirka: 600 North Wolfe Street, Phipps Building Suite 279, Baltimore, MD 21287.
Dr. Lauer: 615 North Wolfe Street, E6003, Baltimore, MD 21231.
Dr. Laeyendecker: 855 North Wolfe Street, Rangos Building, Room 538A, Baltimore, MD 21205.
Dr. Boon: 624 North Broadway, Room 888, Baltimore, MD 21215.
Dr. Lessler: 615 North Wolfe Street, E6545, Baltimore, MD 21231.
Author Contributions: Conception and design: L.M. Kucirka, S.A. Lauer, J. Lessler.
Analysis and interpretation of the data: L.M. Kucirka, S.A. Lauer, O. Laeyendecker, J. Lessler.
Drafting of the article: L.M. Kucirka, S.A. Lauer, J. Lessler.
Critical revision of the article for important intellectual content: L.M. Kucirka, O. Laeyendecker, D. Boon, J. Lessler.
Final approval of the article: L.M. Kucirka, S.A. Lauer, O. Laeyendecker, D. Boon, J. Lessler.
Statistical expertise: L.M. Kucirka, S.A. Lauer, J. Lessler.
Obtaining of funding: J. Lessler.
Administrative, technical, or logistic support: O. Laeyendecker, J. Lessler.
Collection and assembly of data: L.M. Kucirka, S.A. Lauer, D. Boon.
This article was published at Annals.org on 13 May 2020.
* Drs. Kucirka and Lauer contributed equally to this work.
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