Continual mutations in the SARS coronavirus 2 (SARS-CoV-2) genome over time have led to the emergence of waves of infection from variants throughout the COVID-19 pandemic [1]. Whether differences in severity exist amongst variants remains unclear. Evidence to date has suggested that Delta causes more severe disease than earlier variants [2], [3], [4], that Omicron and its sublineages cause less severe disease [5], [6], [7], [8], [9], [10], and that COVID-19 in children is less severe than in adults, regardless of the infecting variant [11]. However, the epidemiologic and genomic bases underlying these reported differences in variant severity remain unexplored.

Here we aimed to investigate differential COVID-19 outcomes in association with infections by SARS-CoV-2 variants in children and adults. We sequenced the SARS-CoV-2 genome, identified the infecting variant in 6916 upper respiratory swabs from patients across five hospitals, and collected relevant clinical, demographic, and laboratory metadata from electronic medical records for comparative analyses of age-related differences in severity and symptomatology. Multivariable logistic regression was used to investigate variant associations with more severe infection for inpatients hospitalized for COVID-19 and symptomatic versus asymptomatic infection for outpatients. We also examined associations of SARS-CoV-2 variant severity with lineage using phylogenetic and genomic analyses.