Relative Virulence of SARS-CoV-2 Among Vaccinated and Unvaccinated Individuals Hospitalized with SARS-CoV-2.

ABSTRACT

BACKGROUND: The rapid development of safe and effective vaccines against the SARS-CoV-2 virus has been a singular scientific achievement. Confounding due to health seeking behaviours, circulating variants, and differential testing by vaccination status may bias analyses towards an apparent increase in infection severity following vaccination. METHODS: We used data from Ontario, Canada's Case and Contact Management database, merged to a provincial vaccination dataset (COVaxON) to create a time-matched cohort of individuals who were hospitalized with SARS-CoV-2 infection. Vaccinated individuals were matched to up to five unvaccinated individuals based on test date. Risk of ICU admission and death were evaluated using conditional logistic regression. Unmatched exploratory analyses were performed to identify sources of heterogeneity in vaccine effects. RESULTS: In 20,064 individuals (3,353 vaccinated and 16,711 unvaccinated) hospitalized with infection due to SARS-CoV-2 between January 1st, 2021 and January 5th, 2022, vaccination with 1, 2, or 3 doses significantly reduced the risk of ICU admission and death. An inverse dose-response relationship was observed between vaccine doses received and both outcomes (adjusted odds ratio (aOR) per additional dose for ICU admission 0.66, 95% CI 0.62 to 0.71; aOR for death 0.78, 95% CI 0.72 to 0.84). Reduction in risk was greater for ICU admission than for death (P for heterogeneity <0.05). INTERPRETATION: We identified decreased virulence of SARS-CoV-2 infections in vaccinated individuals, even when vaccines failed to prevent infection sufficiently severe to cause hospitalization. Even with diminished efficacy of vaccines against infection with novel VOCs, vaccines remain an important tool for reduction of ICU admission and mortality.