In the current COVID-19 landscape dominated by Omicron subvariants, understanding the timing and efficacy of vaccination against emergent lineages is crucial for planning future vaccination campaigns, yet detailed studies stratified by subvariant, vaccination timing, and age groups are scarce. This retrospective study analyzed COVID-19 cases from December 2021 to January 2023 in Catalonia, Spain, focusing on vulnerable populations affected by variants BA.1, BA.2, BA.5, and BQ.1 and including two national booster campaigns. Our database includes detailed information such as dates of diagnosis, hospitalization and death, last vaccination, and cause of death, among others. We evaluated the impact of vaccination on disease severity by age, variant, and vaccination status, finding that recent vaccination significantly mitigated severity across all Omicron subvariants, although efficacy waned six months post-vaccination, except for BQ.1, which showed more stable levels. Unvaccinated individuals had higher hospitalization and mortality rates. Our results highlight the importance of periodic vaccination to reduce severe outcomes, which are influenced by variant and vaccination timing. Although the seasonality of COVID-19 is uncertain, our analysis suggests the potential benefit of annual vaccination in populations >60 years old, probably in early fall, if COVID-19 eventually exhibits a major peak similar to other respiratory viruses.
