Risks of Severe Acute Respiratory Syndrome Coronavirus 2 JN.1 Infection and Coronavirus Disease 2019-Associated Emergency Department Visits/Hospitalizations Following Updated Boosters and Prior Infection: A Population-Based Cohort Study

Background Data on protection afforded by updated coronavirus disease 2019 (COVID-19) vaccines (bivalent/XBB 1.5 monovalent) against the emergent JN.1 variant remain limited.Methods We conducted a retrospective population-based cohort study among all boosted Singaporeans aged >= 18 years during a COVID-19 wave predominantly driven by JN.1, from 26 November 2023 to 13 January 2024. Multivariable Cox regression was used to assess risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-associated emergency department (ED) visits/hospitalizations, stratified by vaccination status/prior infection; with individuals last boosted >= 1 year used as the reference category. Vaccination and infection status were classified using national registries.Results A total of 3 086 562 boosted adult Singaporeans were included in the study population, accounting for 146 863 476 person-days of observation. During the JN.1 outbreak, 28 160 SARS-CoV-2 infections were recorded, with 2926 hospitalizations and 3747 ED visits. Compared with individuals last boosted >= 1 year earlier with ancestral monovalent vaccines, receipt of an updated XBB.1.5 booster 8-120 days earlier was associated with lower risk of JN.1 infection (adjusted hazard ratio [aHR], 0.59 [95% confidence interval (CI), .52-.66]), COVID-19-associated ED visits (0.50 [.34-.73]), and hospitalizations (0.58 [.37-.91]), while receipt of a bivalent booster 121-365 days earlier was associated with lower risk of JN.1 infection (0.92 [.88-.95]) and ED visits (0.80 [.70-.90]). Lower risk of COVID-19 hospitalization during the JN.1 outbreak (aHR, 0.57 [95% CI, .33-.97]) was still observed following receipt of an updated XBB.1.5 booster 8-120 days earlier, even when analysis was restricted to previously infected individuals.Conclusions Recent receipt of updated boosters conferred protection against SARS-CoV-2 infection and ED visits/hospitalizations during a JN.1 variant wave, in both previously infected and uninfected individuals. Annual booster doses confer protection during COVID-19 endemicity. Receipt of updated XBB1.5 vaccines 8-120 days earlier was associated with lower risk of severe acute respiratory syndrome coronavirus 2 infection, emergency department visits and hospitalizations amongst boosted adult Singaporeans during a JN.1 wave.