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The SARS-CoV-2 omicron variant has rapidly spread throughout the world, including in countries with high vaccination rates. As populations increasingly include individuals with both vaccination-driven and infection-driven immunity, it becomes important to understand the differential protection associated with diverse immune histories. Although studies assessing long-term immunity after omicron infection are not yet possible, population-wide studies done in the context of previous variants of concern can be highly informative. In this article, Peter Nordström and colleagues use Swedish national infection and vaccination registers to assess population-wide protection from SARS-CoV-2 infection. They showed that infection-associated immunity was 95% protective against subsequent reinfection during 20 months of follow-up compared with no immunity. Regardless, SARS-CoV-2 infection is clearly a significant contributor to protective immunity, and its interaction with vaccination warrants further longitudinal research, ultimately providing insights to drive proactive health policies and measures for optimal population-wide immunity in this pandemic.