SARS-CoV-2 Shedding Dynamics Across the Respiratory Tract, Sex, and Disease Severity for Adult and Pediatric COVID-19

Chen, P. Z.; Bobrovitz, N.; Premji, Z.; Koopmans, M.; Fisman, D. N.; Gu, F. X.

Background: SARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) remain unclear. Objective: To analyze SARS-CoV-2 shedding dynamics across COVID-19 severity, the respiratory tract, sex and age cohorts (aged 0 to 17 years, 18 to 59 years, and 60 years or older). Design: Systematic review and pooled analyses. Setting: MEDLINE, EMBASE, CENTRAL, Web of Science Core Collection, medRxiv and bioRxiv were searched up to 20 November 2020. Participants: The systematic dataset included 1,266 adults and 136 children with COVID-19. Measurements: Case characteristics (COVID-19 severity, age and sex) and quantitative respiratory viral loads (rVLs). Results: In the URT, adults with severe COVID-19 had higher rVLs at 1 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 post-symptom-onset rVLs 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. Limitation: Limited data on case comorbidities and few samples in some cohorts. Conclusion: High, persistent LRT shedding of SARS-CoV-2 characterized severe COVID-19 in adults. After symptom onset, severe cases tended to have higher URT shedding than their nonsevere counterparts. Disease severity, rather than age or sex, predicted SARS-CoV-2 kinetics. LRT specimens should more accurately prognosticate COVID-19 severity than URT specimens. Primary Funding Source: Natural Sciences and Engineering Research Council.