Background: Evidence on the durability of the protection of a fourth dose of a monovalent or bivalent messenger ribonucleic acid (mRNA) vaccine against coronavirus disease 2019 (COVID-19) among older people during the predominant Omicron period is needed.
Methods: We performed a population-based cohort study in Norway covering the time from 1 July 2022 to 15 January 2023, including individuals ≥75 years of age who had received at least a third dose. Using Cox proportional hazard models on severe COVID-19-associated outcome measures and all-cause mortality, we estimated the vaccine effectiveness of mono- and bivalent vaccines, comparing fourth- to third-dose recipients (>24 weeks ago). Vaccine status was included as a time-varying covariate and models were adjusted for potential confounders.
Results: We included 408 073 individuals. A fourth dose with either monovalent or bivalent mRNA vaccine showed increased protection against COVID-19-associated mortality relative to a third dose in individuals ≥75 years of age. We estimated a protective effect for the bivalent BA.1 vaccine [adjusted hazard ratio (aHR) 0.08, 95% CI 0.02-0.32] relative to the bivalent BA.4-5 (aHR 0.27, 95% CI 0.14-0.56) and a monovalent dose (aHR 0.34, 95% CI 0.26-0.45) 2-9 weeks after vaccination compared with recipients with a third dose >24 weeks ago. The increased protective effect waned with no added protection for the monovalent vaccine after 33 weeks compared with a third dose.
Conclusions: Our results indicate an increased protective effect of a fourth dose against severe outcomes compared with a third dose, with decreasing effect with time since the last dose.
Keywords: Omicron; SARS-CoV-2; bivalent vaccine; booster dose; vaccine effectiveness.
© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.