Bivalent mRNA vaccine effectiveness against COVID-19 infections, hospitalisations and deaths in Portugal: a cohort study based on electronic health records, September 2022 to May 2023

In Portugal, a bivalent COVID-19 vaccine booster was recommended for those with complete primary COVID-19 vaccination, starting on September 6 2022. This study aims to estimate the mRNA bivalent vaccine effectiveness (VE) against COVID-19 infection, hospitalisation and death in the Portuguese population aged 65 and more years with a follow-up of more than six months. MethodsWe used a cohort approach to analyse six electronic health registries using deterministic linkage. The follow-up period comprehend September 2022 to May 2023. The outcomes included SARS-CoV-2 infection, COVID-19-related hospitalisation and death. Individuals were considered vaccinated 14 days following a bivalent mRNA COVID-19 vaccine uptake. For each outcome, COVID-19 bivalent VE was estimated as one minus the confounder adjusted hazard ratio of bivalent vaccine vs no bivalent vaccine, estimated by Cox regression with time-dependent vaccine exposure. ResultsIn the [≥] 80 year-olds, bivalent VE was 23.2 (95%CI: 20.1 to 26.2), 41.3 (95%CI: 34.5 to 47.5) and 50.3 (44.6 to 55.3), against infection, COVID-19-related hospitalisation and death, respectively. In the 65-79 year-old, bivalent VE against infection was 37.7 (35.5 to 39.8), 58.5 (95%CI: 51.9 to 64.2) against hospitalisation and 65.1 (95%CI: 59 to 70.4) against death. Vaccine effectiveness decay was observed for both age groups and in all outcomes, up to 6 months of vaccine uptake. ConclusionsIn a population with a high risk of SARS-CoV-2 complications, we observed moderate bivalent VE estimates against severe COVID-19 and low protection against infection. The lower VE estimates observed in the [≥] 80 year-olds should be interpreted in light of the reference group used for the estimation, i.e., individuals with high vaccine coverage (both primary series and multiple boosters). Significant VE decay was observed up to six months of vaccine uptake, which should be considered when preparing future vaccination campaigns.