Effectiveness of COVID-19 vaccines against hospitalization and death in Canada: A multiprovincial test-negative design study

Background: A major goal of COVID-19 vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of mRNA and ChAdOx1 COVID-19 vaccines against severe outcomes in four Canadian provinces between December 2020 and September 2021. Methods: We conducted this multiprovincial retrospective test-negative study among community-dwelling adults aged [≥]18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random effects models. Results: We included 2,508,296 tested subjects, with 31,776 COVID-19 hospitalizations and 5,842 deaths. Vaccine effectiveness was 83% after a first dose, and 98% after a second dose, against both hospitalization and death (separately). Against severe outcomes (hospitalization or death), effectiveness was 87% (95%CI: 71%-94%) [≥]84 days after a first dose of mRNA vaccine, increasing to 98% (95%CI: 96%-99%) [≥]112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95%CI: 75%-94%) [≥]56 days after a first dose, increasing to 97% (95%CI: 91%-99%) [≥]56 days after a second dose. Lower one-dose effectiveness was observed for adults aged [≥]80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules, and against Alpha, Gamma, and Delta variants. Conclusions: Two doses of mRNA or ChAdOx1 vaccines provide excellent protection against severe outcomes of hospitalization and death.