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

PLoS Biol. 2021 Jul 12;19(7):e3001333. doi: 10.1371/journal.pbio.3001333. eCollection 2021 Jul.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Athletes
  • Basketball
  • COVID-19 / diagnosis*
  • COVID-19 / epidemiology
  • COVID-19 / pathology
  • COVID-19 / virology
  • COVID-19 Nucleic Acid Testing / statistics & numerical data*
  • Convalescence
  • Humans
  • Male
  • Prospective Studies
  • Public Health / methods
  • RNA, Viral / genetics*
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / growth & development
  • Severity of Illness Index
  • United States / epidemiology
  • Virus Replication / genetics*
  • Virus Shedding / genetics*

Substances

  • RNA, Viral

Grant support

This study was funded by the NWO Rubicon 019.181EN.004 (CBFV), a clinical research agreement with the NBA and NBPA (NDG), the Huffman Family Donor Advised Fund (NDG), Fast Grant funding support from the Emergent Ventures at the Mercatus Center, George Mason University (NDG), and the Morris-Singer Fund for the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health (YHG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.