Viral Dynamics of Acute SARS-CoV-2 Infection and Applications to Diagnostic and Public Health Strategies

Authors

Stephen M. Kissler, Harvard T.H. Chan School of Public Health
Joseph R. Fauver, University of Nebraska Medical CenterFollow
Christina Mack, IQVIA
Scott W. Olesen, Harvard T.H. Chan School of Public Health
Caroline Tai, IQVIA
Kristin Y. Shiue, IQVIA
Chaney C. Kalinich, Yale School of Public Health
Sarah Jednak, University of Michigan School of Public Health
Isabel M. Ott, Yale School of Public Health
Chantal B. F. Vogels, Yale School of Public Health
Jay Wohlgemuth, Quest Diagnostics
James Weisberger, Bioreference Laboratories
John DiFiori, Hospital for Special Surgery
Deverick J. Anderson, Duke Center for Antimicrobial Stewardship and Infection Prevention
Jimmie Mancell, University of Tennessee Health Science Center
David D. Ho, Columbia University Vagelos College of Physicians and Surgeons
Nathan D. Grubaugh, Yale School of Public Health
Yonatan H. Grad, Harvard T.H. Chan School of Public Health

Document Type

Article

Journal Title

PLoS Biology

Publication Date

2021

Volume

19

Abstract

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found that viral RNA concentrations peaked an average of 3.3 days (95% credible interval [CI] 2.5, 4.2) after first possible detectability at a cycle threshold value of 22.3 (95% CI 20.5, 23.9). The viral clearance phase lasted longer for symptomatic individuals (10.9 days [95% CI 7.9, 14.4]) than for asymptomatic individuals (7.8 days [95% CI 6.1, 9.7]). A second test within 2 days after an initial positive PCR test substantially improves certainty about a patient's infection stage. The effective sensitivity of a test intended to identify infectious individuals declines substantially with test turnaround time. These findings indicate that SARS-CoV-2 viral concentrations peak rapidly regardless of symptoms. Sequential tests can help reveal a patient's progress through infection stages. Frequent, rapid-turnaround testing is needed to effectively screen individuals before they become infectious.

DOI Link

10.1371/journal.pbio.3001333

ISSN

1545-7885

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Kissler, Stephen M.; Fauver, Joseph R.; Mack, Christina; Olesen, Scott W.; Tai, Caroline; Shiue, Kristin Y.; Kalinich, Chaney C.; Jednak, Sarah; Ott, Isabel M.; Vogels, Chantal B. F.; Wohlgemuth, Jay; Weisberger, James; DiFiori, John; Anderson, Deverick J.; Mancell, Jimmie; Ho, David D.; Grubaugh, Nathan D.; and Grad, Yonatan H., "Viral Dynamics of Acute SARS-CoV-2 Infection and Applications to Diagnostic and Public Health Strategies" (2021). Journal Articles: Epidemiology. 151.
https://digitalcommons.unmc.edu/coph_epidem_articles/151