Effectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes

We estimated the effectiveness of booster doses of monovalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults in Ontario, Canada. We used a test-negative design to estimate vaccine effectiveness (VE) against hospitalization or death among SARS-CoV-2-tested adults aged ≥50 years from January 2 to October 1, 2022, stratified by age and time since vaccination. We also compared during BA.1/BA.2 and BA.4/BA.5 sublineage predominance. We included 11,060 cases and 62,880 tested unvaccinated adults. VE was 91–98% for 59 days after a third dose, waned to 76–87% after ≥240 days, was restored to 92–97% for 59 days after a fourth dose, and wanted to 86-89% after ≥120 days. VE was lower and declined faster during BA.4/BA.5 versus BA.1/BA.2 predominance, particularly after ≥120 days. Here we show that booster doses of monovalent mRNA COVID-19 vaccines restored strong protection against severe outcomes for at least 3 months after vaccination. Across the entire study period, protection declined slightly over time, but waned more during BA.4/BA.5 predominance.