Publication date: May 20, 2025

SARS-CoV-2 vaccines are highly effective in preventing severe COVID-19 but require boosting to maintain protection. Changes to circulating variants and prevalent natural immunity may impact on real-world effectiveness of boosters. With NHS England approval, we used linked routine clinical data from >24 million patients to evaluate the effectiveness of the 2022 combined COVID-19 autumn booster and influenza vaccine campaign in non-clinically vulnerable 50-year-olds in England using a regression discontinuity design. Our primary outcome was a composite of 6-week COVID-19 emergency attendance, COVID-19 unplanned hospitalisation, or death. By 26 November 2022, booster vaccine coverage was 11. 1 % at age 49. 75 years increasing to 39. 7 % at age 50. 25 years. The estimated effect of the campaign on the risk of the primary outcome in 50-year-olds during weeks 7-12 after the start of the campaign was -0. 4 per 100,000 (95 % CI -7. 8, 7. 1). The results were similar when using different follow-up start dates or when estimating the effect of vaccination (rather than the campaign). This study found little evidence that the autumn 2022 vaccination campaign in England was associated with a reduction in severe COVID-19-related outcomes among non-clinically vulnerable 50-year-olds. Possible explanations include the low risk of severe outcomes and substantial pre-existing vaccine- and infection-induced immunity. The booster campaign may have had effects beyond those we estimated, including reducing virus transmission and incidence of mild or moderate COVID-19.

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