Viral variant but not host factors associate with SARS-CoV-2 viral kinetics

Abstract

BACKGROUND: It is challenging to assess SARS-CoV-2 viral kinetics amidst viral variant evolution and changes in population-level immunity. However, understanding the relationship between host factors and viral replication deepens our understanding of viral fitness. METHODS: In CoVPN 5001, we enrolled N = 953 adults diagnosed with acute SARS-CoV-2 from July 2020 to July 2022 across 51 sites. We confirmed SARS-CoV-2 infection by RT-PCR and identified the variant via viral genome sequencing. Using multivariable linear regression and median regression, we studied the association between host factors and either observed peak viral load (VL) or clinical viral shedding, respectively, accounting for viral variant effects in a demographically and clinically diverse longitudinal cohort. RESULTS: In this observational study, we determine that while host factors, including age, BMI, sex, medical comorbidities, and HIV, have no significant associations with either observed peak VL or clinical viral shedding in the nasopharynx, viral variant is significantly associated with observed peak VL and clinical viral shedding. We show that neither observed peak VL nor shedding duration predict evolutionary success since the dominant variants in the SARS-CoV-2 pandemic did not all align with the variants with the highest peak and longest shedding duration. CONCLUSIONS: Altogether, our work shows that observed peak VL and shedding duration should be cautiously interpreted as predictors of viral fitness.