Age-Specific Changes in Virulence Associated with SARS-CoV-2 Variants of Concern

Background: Novel variants of concern (VOCs) have been associated with both increased infectivity and virulence of SARS-CoV-2. The virulence of SARS-CoV-2 is closely linked to age. Whether relative increases in virulence of novel VOCs is similar across the age spectrum, or is limited to some age groups, is unknown. Methods: We created a retrospective cohort of people in Ontario, Canada testing positive for SARS-CoV-2 and screened for VOCs, with dates of test report between February 7 and August 30, 2021 (n=233,799). Cases were classified as N501Y-positive VOC, probable Delta VOC, or VOC undetected. We constructed age-specific logistic regression models to evaluate the effects of N501Y-postive or Delta VOC infections on infection severity, using hospitalization, intensive care unit (ICU) admission, and death as outcome variables. Models were adjusted for sex, time, health unit, vaccination status, comorbidities, immune compromise, long-term care residence, healthcare worker status, and pregnancy. Results: Infection with either N501Y-positive or Delta VOCs was associated with significant elevations in risk of hospitalization, ICU admission, and death in younger and older adults, compared to infections where a VOC was not detected. Delta VOC increased hospitalization risk in children under 10 by a factor of 2.5 (adjusted odds ratio, 95% confidence interval: 1.2 to 5.1) compared to non-VOC. For most VOC-outcome combinations there was no heterogeneity in adverse outcomes by age. However, there was an inverse relationship between age and relative increase in risk of death with delta VOC, with younger age groups showing a greater relative increase in risk of death than older individuals. Interpretation: SARS-CoV-2 VOCs appear to be associated with increased relative virulence of infection in all age groups, though low absolute numbers of outcomes in younger individuals make estimates in these groups imprecise.