1. Epidemiology and Global Health
  2. Microbiology and Infectious Disease

SARS-CoV-2 shedding dynamics across the respiratory tract, sex, and disease severity for adult and pediatric COVID-19

  1. Paul Z Chen
  2. Niklas Bobrovitz
  3. Zahra Premji
  4. Marion Koopmans
  5. David N Fisman
  6. Frank X Gu  Is a corresponding author
  1. University of Toronto, Canada
  2. University of Victoria, Canada
  3. Erasmus University Medical Center, Netherlands
https://doi.org/10.7554/eLife.70458
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Cite this article
  1. Paul Z Chen
  2. Niklas Bobrovitz
  3. Zahra Premji
  4. Marion Koopmans
  5. David N Fisman
  6. Frank X Gu
(2021)
SARS-CoV-2 shedding dynamics across the respiratory tract, sex, and disease severity for adult and pediatric COVID-19
eLife 10:e70458.
https://doi.org/10.7554/eLife.70458
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Abstract

Background:

Previously, we conducted a systematic review and
 analyzed the respiratory kinetics of SARS-CoV-2 (P. Z. Chen et al., 2021). How age, sex and
 COVID-19 severity interplay to influence the shedding dynamics of SARS-CoV-2, however,
 remains poorly understood.

Methods:

We updated our systematic
 dataset, collected individual case characteristics and conducted stratified analyses of
 SARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) across
 COVID-19 severity, sex and age groups (aged 0 to 17 years, 18 to 59 years, and 60 years or
 older).

Results:

The systematic dataset included 1,266 adults
 and 136 children with COVID-19. Our analyses indicated that high, persistent LRT shedding of
 SARS-CoV-2 characterized severe COVID-19 in adults. Severe cases tended to show slightly
 higher URT shedding post-symptom onset, but similar rates of viral clearance, when compared
 to nonsevere infections. After stratifying for disease severity, sex and age (including
 child vs. adult) were not predictive of respiratory shedding. The estimated accuracy for
 using LRT shedding as a prognostic indicator for COVID-19 severity was up to 81%, whereas it
 was up to 65% for URT shedding.

Conclusions:

Virological
 factors, especially in the LRT, facilitate the pathogenesis of severe COVID-19. Disease
 severity, rather than sex or age, predict SARS-CoV-2 kinetics. LRT viral load may
 prognosticate COVID-19 severity in patients before the timing of deterioration, and should
 do so more accurately than URT viral load.

Funding:

Natural
 Sciences and Engineering Research Council of Canada (NSERC) DiscoveryGrant, NSERC Senior
 Industrial Research Chair and the Toronto COVID-19 Action Fund.

Data availability

The systematic dataset and model outputs from this study can be download from a public repository (https://zenodo.org/record/5209064). The code generated during this study is available at GitHub (https://github.com/paulzchen/sars2-shedding). The systematic review protocol was prospectively registered on PROSPERO (registration number, CRD42020204637).

The following data sets were generated

Article and author information

Author details

  1. Paul Z Chen

    Chemical Engineering & Applied Chemistry, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5261-1610

  2. Niklas Bobrovitz

    Medicine, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.

  3. Zahra Premji

    University of Victoria, Victoria, Canada
    Competing interests
    No competing interests declared.

  4. Marion Koopmans

    Department of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands
    Competing interests
    No competing interests declared.

  5. David N Fisman

    Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
    Competing interests
    David N Fisman, DNF reports serving on advisory boards of Seqirus, Sanofi Pasteur, Pfizer,and AstraZeneca, and consulting for the Ontario Nurses Association, Elementary Teachers' Federation of Ontario, JP Morgan­Chase, WE Foundation, and Farallon Capital, outside the submitted work..

  6. Frank X Gu

    Chemical Engineering & Applied Chemistry, University of Toronto, Toronto, Canada
    For correspondence
    f.gu@utoronto.ca
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8749-9075

Funding

Natural Sciences and Engineering Research Council of Canada (Vanier Scholarship (608544))

  • Paul Z Chen

Canadian Institutes of Health Research (Canadian COVID-19 Rapid Research Fund (OV4-170360))

  • David N Fisman

Natural Sciences and Engineering Research Council of Canada (Senior Industrial Research Chair)

  • Frank X Gu

Toronto COVID-19 Action Fund

  • Frank X Gu

The funders had no role in study design, collection or interpretation of the data, preparation of the manuscript, or the decision to submit the manuscript for publication.

Copyright

© 2021, Chen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Paul Z Chen
  2. Niklas Bobrovitz
  3. Zahra Premji
  4. Marion Koopmans
  5. David N Fisman
  6. Frank X Gu
(2021)
SARS-CoV-2 shedding dynamics across the respiratory tract, sex, and disease severity for adult and pediatric COVID-19
eLife 10:e70458.
https://doi.org/10.7554/eLife.70458

Share this article

https://doi.org/10.7554/eLife.70458

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Further reading

    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets and aerosols

    Paul Z Chen, Niklas Bobrovitz ... Frank X Gu
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    Background:

    Which virological factors mediate overdispersion in the transmissibility of emerging viruses remains a long-standing question in infectious disease epidemiology.

    Methods:

    Here, we use systematic review to develop a comprehensive dataset of respiratory viral loads (rVLs) of SARS-CoV-2, SARS-CoV-1 and influenza A(H1N1)pdm09. We then comparatively meta-analyze the data and model individual infectiousness by shedding viable virus via respiratory droplets and aerosols.

    Results:

    The analyses indicate heterogeneity in rVL as an intrinsic virological factor facilitating greater overdispersion for SARS-CoV-2 in the COVID-19 pandemic than A(H1N1)pdm09 in the 2009 influenza pandemic. For COVID-19, case heterogeneity remains broad throughout the infectious period, including for pediatric and asymptomatic infections. Hence, many COVID-19 cases inherently present minimal transmission risk, whereas highly infectious individuals shed tens to thousands of SARS-CoV-2 virions/min via droplets and aerosols while breathing, talking and singing. Coughing increases the contagiousness, especially in close contact, of symptomatic cases relative to asymptomatic ones. Infectiousness tends to be elevated between 1 and 5 days post-symptom onset.

    Conclusions:

    Intrinsic case variation in rVL facilitates overdispersion in the transmissibility of emerging respiratory viruses. Our findings present considerations for disease control in the COVID-19 pandemic as well as future outbreaks of novel viruses.

    Funding:

    Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant program, NSERC Senior Industrial Research Chair program and the Toronto COVID-19 Action Fund.

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