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

Abstract

Background: SARS-CoV-2 shedding dynamics influence the risk of transmission and clinical manifestations of COVID-19. Yet, the relationships between SARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) and age, sex and COVID-19 severity remain unclear.Methods: Using systematic review, we developed a dataset of case characteristics (age, sex and COVID-19 severity) and quantitative respiratory viral loads (rVLs). We then conducted stratified analyses to assess SARS-CoV-2 shedding across disease course, COVID-19 severity, the respiratory tract, 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. In the URT, adults with severe COVID-19 had higher rVLs at 1 day from symptom onset (DFSO) than adults (P = 0.005) or children (P = 0.017) with nonsevere illness. Between 1-10 DFSO, severe adults had comparable rates of SARS-CoV-2 clearance from the URT as nonsevere adults (P = 0.479) and nonsevere children (P = 0.863). In the LRT, severe adults showed higher rVLs post-symptom onset than nonsevere adults (P = 0.006). In the analyzed period (4-10 DFSO), severely affected adults had no significant trend in SARS-CoV-2 clearance from LRT (P = 0.105), whereas nonsevere adults showed a clear trend (P < 0.001). After stratifying for disease severity, sex and age (including child vs. adult) were not predictive of the duration of respiratory shedding. The estimated accuracy for using URT shedding as a prognostic indicator for COVID-19 severity was up to 65%, whereas it was up to 81% for LRT shedding.Conclusions: High, persistent LRT shedding of SARS-CoV-2 characterized severe COVID-19 in adults. After symptom onset, severe cases tended to have slightly higher URT shedding than their nonsevere counterparts. Disease severity, rather than age or sex, predicted SARS-CoV-2 kinetics. LRT specimens more accurately prognosticate COVID-19 severity than do URT specimens.Funding: Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant, NSERC Senior Industrial Research Chair and the Toronto COVID-19 Action Fund.