PLoS Biology (Jul 2021)

Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies.

  • Stephen M Kissler,
  • Joseph R Fauver,
  • Christina Mack,
  • Scott W Olesen,
  • Caroline Tai,
  • Kristin Y Shiue,
  • Chaney C Kalinich,
  • Sarah Jednak,
  • Isabel M Ott,
  • Chantal B F Vogels,
  • Jay Wohlgemuth,
  • James Weisberger,
  • John DiFiori,
  • Deverick J Anderson,
  • Jimmie Mancell,
  • David D Ho,
  • Nathan D Grubaugh,
  • Yonatan H Grad

DOI
https://doi.org/10.1371/journal.pbio.3001333
Journal volume & issue
Vol. 19, no. 7
p. e3001333

Abstract

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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.