Abstract
BACKGROUND: Previously, we conducted a systematic review and analyzed the respiratory kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Chen et al., 2021). How age, sex, and coronavirus disease 2019 (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 0-17 years, 18-59 years, and 60 years or older). RESULTS: The systematic dataset included 1266 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, predicts 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) Discovery Grant, NSERC Senior Industrial Research Chair, and the Toronto COVID-19 Action Fund.