Abstract
The SARS-CoV-2 variant Omicron emerged in late 2021. In British Columbia (BC), Canada, and globally, three genetically distinct sub-variants of Omicron, BA.1, BA.2 and BA.5, emerged and became dominant successively within an 8-month period. SARS-CoV-2 sub-variants continue to circulate in the population, acquiring new mutations that have the potential to alter infectivity, immunity and disease severity. Here, we report a propensity-matched severity analysis from residents of BC over the course of the Omicron wave, including 39,237 individuals infected with BA.1, BA.2 or BA.5 based on paired high-quality sequence data and linked to comprehensive clinical outcomes data between Dec. 23, 2021 and August 31, 2022. Relative to BA.1, BA.2 cases were associated with a 15% and 28% lower risk of hospitalization and Intensive Care Unit (ICU) admission (aHRhospital=1.17; 95%CI=1.096-1.252; aHRICU=1.368; 95%CI=1.152-1.624), whereas BA.5 infections were associated with a 1 8% higher risk of hospitalization (aHRhospital=1.18; 95%CI=1.133-1.224) after accounting for age, sex, co-morbidities, vaccination status, geography and social determinants of health. Phylogenetic analysis revealed no specific sub-clades associated with more severe clinical outcomes for any Omicron sub-variant. In summary, BA.1, BA.2 and BA.5 sub-variants were associated with differences in clinical severity, emphasizing how variant-specific monitoring programs remain critical components of patient and population-level public health responses as the pandemic continues.
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