Relative Effectiveness and Waning of a Third Dose of mRNA COVID-19 Vaccine in Medicare Beneficiaries Aged 65 Years and Older during the BA.1/BA.2 Omicron Period.

BACKGROUND We assessed the added benefit and waning effectiveness of a third COVID-19 vaccine dose (original formula) for preventing COVID-19-related outcomes. METHODS We used Medicare claims data to conduct a retrospective cohort study in U.S. community-dwelling Medicare Fee-for-Service beneficiaries aged ≥65 years during the BA.1/BA.2 Omicron period (December 19, 2021 - March 26, 2022). We estimated relative vaccine effectiveness (RVE) of 3 versus 2 doses of mRNA COVID-19 vaccines using marginal structural Cox regression models. RESULTS Among 8,135,020 eligible beneficiaries, 73.3% were 3-dose vaccinated by March 26, 2022. At 14-60 days since vaccination, a third dose provided significant added benefit against COVID-19-related hospitalization for Moderna (RVE: 77.2%; 95% confidence interval (CI): 76.0%, 78.4%) and Pfizer-BioNTech (RVE: 72.5%; 95% CI: 70.8%, 74.0%). Added benefit was lower >120 days. For those with prior medically attended COVID-19 diagnoses, Pfizer-BioNTech provided an added benefit for 120 days, while Moderna provided some added benefit >120 days. Added benefit for either vaccine was higher against death compared to less severe outcomes, which still decreased >120 days. CONCLUSIONS A third dose COVID-19 vaccine provided significant added benefit against COVID-19-related hospitalization and death, even for beneficiaries with prior medically attended COVID-19 diagnoses. This added benefit decreased after 4 months.