Effectiveness and durability of a second COVID-19 booster against severe outcomes among older people in Norway: a population-based cohort study comparing mono- and bivalent booster doses

• Published in: International journal of epidemiology Vol. 52; no. 6; pp. 1716 - 1724
• Main Authors: Stecher, Melanie, Kristoffersen, Anja Bråthen, Lie, Kristian, Andersen, Svein Rune, Meijerink, Hinta, Starrfelt, Jostein
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 25-12-2023
• Subjects: Covid-19; vaccine effectiveness; bivalent vaccine; SARS-CoV-2; Omicron; booster dose
• ISSN: 0300-5771; 1464-3685
• DOI: 10.1093/ije/dyad114

Abstract
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.