Annual variant-targeted vaccination to prevent severe COVID-19 disease in cohorts with vaccine-derived and hybrid immunity.

Kelly, Hoggatt, Lo, Leonard, Boscardin, Kim, Lum, Austin, Byers, Tien, Austin, Bravata, Keyhani. Annual variant-targeted vaccination to prevent severe COVID-19 disease in cohorts with vaccine-derived and hybrid immunity. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2025 Mar 14 DOI: 10.1093/cid/ciaf124.

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Abstract:

BACKGROUND: Current U.S. COVID-19 vaccine recommendations provide guidance for adults to receive at least annual variant-targeted vaccination. We sought to estimate the strength and durability of protection from annual variant-targeted vaccination against severe COVID-19 illness in individuals with vaccine-derived and hybrid immunity. METHODS: We emulated a target trial using an electronic health record-based, propensity-score matched (1:1) cohort of U.S. Veterans. Booster vaccinated adults were eligible for a variant-targeted mRNA booster starting September 1, 2022. Matched sets of those who did and did not receive the variant-targeted booster dose were identified on a weekly basis, and the cohort was followed until August 31, 2023. Outcomes were hospitalization due to COVID-19 pneumonia, and in-hospital severe illness. We fit Cox models, overall and stratified by last documented SARS-CoV-2 infection (pre-Omicron, Omicron), to estimate relative vaccine effectiveness (VE). RESULTS: The propensity-score matched cohort consisted of 1,576,626 COVID-19 booster vaccinated adults. Estimates of relative vaccine effectiveness (rVE) from variant-targeted mRNA booster against hospitalization due to COVID-19 pneumonia were significant and similar in the cohort with vaccine-derived immunity (rVE: 29%; 95%CI: 25%, 34%) and cohort with hybrid immunity (rVE: 38%; 95%CI: 27%, 47%). These protective gains were significant from 0-6 but not 6-12 months after vaccination and during pre-XBB and XBB variant eras. Findings were similar for in-hospital severe illness. CONCLUSION: In cohorts with vaccine-derived and hybrid immunity, modest but significant gains in protection against hospitalization and severe COVID-19 illness were conferred by the annual variant-targeted booster dose but not sustained beyond 6 months.