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

Author

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  • 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

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.Viral dynamics of SARS-CoV-2 infections can inform public health surveillance strategies and clinical care, but the full infection dynamics have remained undescribed. This study presents such data from the National Baseball Association 2019-20 season restart and demonstrates their applications.

Suggested Citation

  • 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 W, 2021. "Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies," PLOS Biology, Public Library of Science, vol. 19(7), pages 1-17, July.
  • Handle: RePEc:plo:pbio00:3001333
    DOI: 10.1371/journal.pbio.3001333
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    References listed on IDEAS

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    1. Carpenter, Bob & Gelman, Andrew & Hoffman, Matthew D. & Lee, Daniel & Goodrich, Ben & Betancourt, Michael & Brubaker, Marcus & Guo, Jiqiang & Li, Peter & Riddell, Allen, 2017. "Stan: A Probabilistic Programming Language," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 76(i01).
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    Cited by:

    1. Anna Maria Cattelan & Lolita Sasset & Federico Zabeo & Anna Ferrari & Lucia Rossi & Maria Mazzitelli & Silvia Cocchio & Vincenzo Baldo, 2022. "Rapid Antigen Test LumiraDx TM vs. Real Time Polymerase Chain Reaction for the Diagnosis of SARS-CoV-2 Infection: A Retrospective Cohort Study," IJERPH, MDPI, vol. 19(7), pages 1-12, March.
    2. Hanyu Li & Kazuki Kuga & Kazuhide Ito, 2022. "SARS-CoV-2 Dynamics in the Mucus Layer of the Human Upper Respiratory Tract Based on Host–Cell Dynamics," Sustainability, MDPI, vol. 14(7), pages 1-18, March.
    3. Junya Sunagawa & Hyeongki Park & Kwang Su Kim & Ryo Komorizono & Sooyoun Choi & Lucia Ramirez Torres & Joohyeon Woo & Yong Dam Jeong & William S. Hart & Robin N. Thompson & Kazuyuki Aihara & Shingo Iw, 2023. "Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Stephen M. Kissler & James A. Hay & Joseph R. Fauver & Christina Mack & Caroline G. Tai & Deverick J. Anderson & David D. Ho & Nathan D. Grubaugh & Yonatan H. Grad, 2023. "Viral kinetics of sequential SARS-CoV-2 infections," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
    5. Yong Dam Jeong & Keisuke Ejima & Kwang Su Kim & Woo Joohyeon & Shoya Iwanami & Yasuhisa Fujita & Il Hyo Jung & Kazuyuki Aihara & Kenji Shibuya & Shingo Iwami & Ana I. Bento & Marco Ajelli, 2022. "Designing isolation guidelines for COVID-19 patients with rapid antigen tests," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    6. Diana Rose E. Ranoa & Robin L. Holland & Fadi G. Alnaji & Kelsie J. Green & Leyi Wang & Richard L. Fredrickson & Tong Wang & George N. Wong & Johnny Uelmen & Sergei Maslov & Zachary J. Weiner & Alexei, 2022. "Mitigation of SARS-CoV-2 transmission at a large public university," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Yun Lin & Bingyi Yang & Sarah Cobey & Eric H. Y. Lau & Dillon C. Adam & Jessica Y. Wong & Helen S. Bond & Justin K. Cheung & Faith Ho & Huizhi Gao & Sheikh Taslim Ali & Nancy H. L. Leung & Tim K. Tsan, 2022. "Incorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmission," Nature Communications, Nature, vol. 13(1), pages 1-8, December.

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