Real-world Effectiveness of Mrna COVID-19 Vaccines among US Nursing Home Residents Aged ≥65 Years in the Pre-Delta and High Delta Periods.

Background Long-term care residents were among the most vulnerable during the COVID-19 pandemic. We estimated vaccine effectiveness of mRNA COVID-19 vaccines in Medicare nursing home residents aged >= 65 years during pre-Delta and high Delta periods.Methods We conducted a retrospective cohort study from 13 December 2020 to 20 November 2021 using Medicare claims data. Exposures included 2 and 3 doses of Pfizer-BioNTech and Moderna COVID-19 vaccines. We used inverse probability weighting and Cox proportional hazards models to estimate absolute and relative vaccine effectiveness.Results Two-dose vaccine effectiveness against COVID-19-related death was 69.8% (95% CI, 65.9%-73.3%) during the pre-Delta period and 55.7% (49.5%-61.1%) during the high Delta period, without adjusting for time since vaccination. We observed substantial waning of effectiveness from 65.1% (54.2%-73.5%) within 6 months from second-dose vaccination to 45.2% (30.6%-56.7%) >= 6 months after second-dose vaccination in the high Delta period. Three doses provided 88.7% (73.5%-95.2%) vaccine effectiveness against death, and the incremental benefit of 3 vs 2 doses was 74.6% (40.4%-89.2%) during high Delta. Among beneficiaries with a prior COVID-19 infection, 3-dose vaccine effectiveness for preventing death was 78.6% (50.0%-90.8%), and the additional protection of 3 vs 2 doses was 70.0% (30.1%-87.1%) during high Delta. Vaccine effectiveness estimates against less severe outcomes (eg, infection) were lower.Conclusions This nationwide real-world study demonstrated that mRNA COVID-19 vaccines provided substantial protection against COVID-19-related death. Two-dose protection waned after 6 months. Third doses during the high Delta period provided significant additional protection for individuals with or without a prior COVID-19 infection. In a nationwide real-world study among nursing home residents, mRNA COVID-19 vaccines provided substantial protection against COVID-19-related death, even among prior COVID-19 survivors. Two-dose protection waned after 6 months. A third dose significantly boosted protection.