Age-Specific Changes in Virulence Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern

Abstract

Background: Novel variants of concern (VOCs) have been associated with both increased infectivity and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virulence of SARS-CoV-2 is closely linked to age. Whether relative increases in virulence of novel VOCs are similar across the age spectrum or are limited to some age groups is unknown.

Methods: We created a retrospective cohort of people in Ontario, Canada, who tested positive for SARS-CoV-2 and were screened for VOCs (n = 259 984) between 7 February 2021 and 31 October 2021. Cases were classified as N501Y-positive VOC, probable Delta VOC, or VOC undetected. We constructed age-specific logistic regression models to evaluate associations between N501Y-postive or Delta VOC infections and infection severity using hospitalization, intensive care unit (ICU) admission, and death as outcome variables. Models were adjusted for sex, comorbidity, vaccination status, and temporal trends.

Results: Infection with either N501Y-positive or Delta VOCs was associated with significant elevations in risk of hospitalization, ICU admission, and death across age groups compared with infections where a VOC was not detected. The Delta VOC increased hospitalization risk in children aged <10 years by a factor of 2.5 (adjusted odds ratio; 95% confidence interval, 1.3 to 5.0) compared with non-VOCs. There was a significant inverse relationship between age and relative increase in risk of death with the Delta VOC, with younger age groups showing a greater relative increase in risk of death than older individuals.

Conclusions: 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.

Keywords: SARS coronavirus-2; age; epidemiology; health outcomes; virulence.

Figure 1.

Forest plot with adjusted ORs for hospitalization, ICU admission, and death by age group for N501Y-positive variant of concern (VOC) infection relative to non-VOC severe acute respiratory syndrome coronavirus 2 infection. Models were adjusted for sex, health unit region, age group, vaccination status, comorbidity, immune compromise, and (in relevant age groups) long-term care residence, healthcare worker status, and pregnancy. Abbreviations: CI, confidence interval; ICU, intensive care unit; OR, odds ratio.

Figure 2.

Forest plot with adjusted ORs for hospitalization, ICU admission, and death by age group for the Delta variant of concern (VOC) infection relative to non-VOC severe acute respiratory syndrome coronavirus 2 infection. Models were adjusted for sex, health unit region, age group, vaccination status, comorbidity, immune compromise, and (in relevant age groups) long-term care residence, healthcare worker status, and pregnancy. Abbreviations: CI, confidence interval; ICU, intensive care unit; OR, odds ratio.