Protection of prior SARS-CoV-2 infection, COVID-19 boosters, and hybrid immunity against Omicron severe illness: A population-based cohort study of five million residents in Canada.

At least three antigenic exposures, achieved by vaccination or infection, confers significant protection against Omicron-associated hospitalization and death in all age groups. Our findings support a third dose for the overall population, regardless of prior infection status, and a fourth dose for the elderly to maintain high level of immunity and substantially reduce risk of severe illness at individual level.