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.

Ramnidip Grewal, Lena Nguyen, Sarah A. Buchan, Sharifa Nasreen, Peter C. Austin, Kevin L. Brown, Deshayne B. Fell, Jonathan B. Gubbay, Kevin L. Schwartz, Mina Tadrous, Kumanan Wilson, Jeffrey C. Kwong