biostudies-literatureKelly JDNational Institute of Allergy and Infectious DiseasesDepartment of Veterans Affairs Clinical Science Research and DevelopmentNational Institute of Allergy and Infectious Diseases (NIAID)NIAID NIH HHSCSRD VA222-230https://www.ebi.ac.uk/biostudies/studies/S-EPMC12448581biostudies-literatureUnknown81(2)<h4>Background</h4>Current coronavirus disease 2019 (COVID-19) vaccine recommendations in the United States (US) 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.<h4>Methods</h4>We emulated a target trial using an electronic health record-based, propensity score-matched (1:1) cohort of US Veterans. Booster-vaccinated adults were eligible for a variant-targeted messenger RNA (mRNA) booster starting 1 September 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 untilClinical infectious diseases : an official publication of the Infectious Diseases Society of AmericaAnnual Variant-Targeted Vaccination to Prevent Severe COVID-19 in Cohorts With Vaccine-Derived and Hybrid Immunity.PMC12448581K23 AI146268CX002417I01 CX002417AI146268Austin CCByers ALHoggatt KJKim HSTien PCBravata DMKeyhani SLeonard SLo NCLum ENKelly JDBoscardin WJAustin PCfalseAnnual Variant-Targeted Vaccination to Prevent Severe COVID-19 in Cohorts With Vaccine-Derived and Hybrid Immunity.<h4>Background</h4>Current coronavirus disease 2019 (COVID-19) vaccine recommendations in the United States (US) 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.<h4>Methods</h4>We emulated a target trial using an electronic health record-based, propensity score-matched (1:1) cohort of US Veterans. Booster-vaccinated adults were eligible for a variant-targeted messenger RNA (mRNA) booster starting 1 September 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 until2025-01-01T00:00:00Z2025 Sep2026-06-03T15:15:11.259Z2026-04-29T03:09:03.563ZS-EPMC124485814008440610.1093/cid/ciaf124