BACKGROUND: After a period of low SARS-CoV-2 activity, viral circulation increased in Europe from May 2024, driven by immune-evasive KP sublineages of the JN.1 variant. We estimated vaccine effectiveness (VE) of the XBB.1.5 dose administered in autumn 2023 against COVID-19-related hospitalisations and deaths in individuals 65 years of age or older during this period.

METHODS: We conducted a multi-country cohort study across six EU nations in the VEBIS-EHR network using linked electronic health records. VE against COVID-19-related hospitalisation and death during June-August 2024 was estimated using Cox regression in a two-stage analysis, adjusting for demographics, comorbidities and prior vaccination history.

RESULTS: Among individuals 65-79 and ≥ 80 years old, respectively, VE of the XBB.1.5 dose ≥ 6 months post administration was 13% (95% CI: -12% to 33%) and 7% (95% CI: -7% to 19%) against hospitalisation and 39% (95% CI: -7% to 65%) and 3% (95% CI: -23% to 23%) against deaths.

CONCLUSIONS: XBB.1.5 vaccination provided minimal residual protection against severe COVID-19 outcomes among adults aged ≥ 65 years more than 6 months after vaccination, during the summer 2024 period of increased SARS-CoV-2 activity.