Kelly, J. DanielLeonard, SamuelBoscardin, W. JohnHoggatt, Katherine J.Lum, Emily N.Austin, Charles C.Byers, AmyTien, Phyllis C.Austin, Peter C.Bravata, Dawn M.Keyhani, Salomeh2024-01-042024-01-042023-05-23Kelly JD, Leonard S, Boscardin WJ, et al. Comparative mRNA booster effectiveness against death or hospitalization with COVID-19 pneumonia across at-risk US Veteran populations. Nat Commun. 2023;14(1):2976. Published 2023 May 23. doi:10.1038/s41467-023-38503-8https://hdl.handle.net/1805/37611Studies of comparative mRNA booster effectiveness among high-risk populations can inform mRNA booster-specific guidelines. The study emulated a target trial of COVID-19 vaccinated U.S. Veterans who received three doses of either mRNA-1273 or BNT162b2 vaccines. Participants were followed for up to 32 weeks between July 1, 2021 to May 30, 2022. Non-overlapping populations were average and high risk; high-risk sub-groups were age ≥65 years, high-risk co-morbid conditions, and immunocompromising conditions. Of 1,703,189 participants, 10.9 per 10,000 persons died or were hospitalized with COVID-19 pneumonia over 32 weeks (95% CI: 10.2, 11.8). Although relative risks of death or hospitalization with COVID-19 pneumonia were similar across at-risk groups, absolute risk varied when comparing three doses of BNT162b2 with mRNA-1273 (BNT162b2 minus mRNA-1273) between average-risk and high-risk populations, confirmed by the presence of additive interaction. The risk difference of death or hospitalization with COVID-19 pneumonia for high-risk populations was 2.2 (0.9, 3.6). Effects were not modified by predominant viral variant. In this work, the risk of death or hospitalization with COVID-19 pneumonia over 32 weeks was lower among high-risk populations who received three doses of mRNA-1273 vaccine instead of BNT162b2 vaccine; no difference was found among the average-risk population and age >65 sub-group.en-USAttribution 4.0 InternationalBNT162 VaccineCOVID-19HospitalizationVeteransArticle