Background: The period from February to June 2021 was one during which initial wild-type SARS-CoV-2 strains were supplanted in Ontario, Canada, first by variants of concern (VOC) with the N501Y mutation (Alpha/B1.1.17, Beta/B.1.351 and Gamma/P.1 variants), and then by the Delta/B.1.617 variant. The increased transmissibility of these VOCs has been documented but data for increased virulence is limited. We used Ontario COVID-19 case data to evaluate the virulence of these VOCs compared to non-VOC SARS-CoV-2 infections, as measured by risk of hospitalization, intensive care unit (ICU) admission, and death. Methods: We created a retrospective cohort of people in Ontarios testing positive for SARS-CoV-2 and screened for VOCs, with dates of test report between February 7 and June 22, 2021 (n=211,197). We constructed mixed effects logistic regression models with hospitalization, ICU admission, and death as outcome variables. Models were adjusted for age, sex, time, comorbidities, and pregnancy status. Health units were included as random intercepts. Results: Compared to non-VOC SARS-CoV-2 strains, the adjusted elevation in risk associated with N501Y-positive variants was 59% (49-69%) for hospitalization; 105% (82-134%) for ICU admission; and 61% (40-87%) for death. Increases with Delta variant were more pronounced: 120% (93-153%) for hospitalization; 287% (198-399%) for ICU admission; and 137% (50-230%) for death. Interpretation: The progressive increase in transmissibility and virulence of SARS-CoV-2 VOCs will result in a significantly larger, and more deadly, pandemic than would have occurred in the absence of VOC emergence.
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