INTRODUCTION: This study evaluated the effectiveness of Moderna's updated mRNA-1273 vaccine targeting the KP.2 variant, compared to people who did not receive any 2024-2025 COVID-19 vaccine, in preventing COVID-19-associated hospitalizations and medically-attended COVID-19 among adults aged ≥ 18 years in the United States during the 2024-2025 season.
METHODS: Data were extracted from linked administrative healthcare claims and electronic health records (EHR) for vaccinations from 23 August 2024 through 23 April 2025 and followed through 30 April 2025. We conducted a retrospective matched cohort study with propensity score weighting to adjust for differences between groups to assess vaccine effectiveness (VE) against COVID-19 outcomes. VE was calculated as 1 minus the hazard ratio (HR) from Cox proportional hazards models.
RESULTS: Overall, 596,248 mRNA-1273 KP.2 vaccine recipients were matched 1:1 to unexposed adults. The mean (standard deviation) age was 63 (17) years, with more than half of the population being 65 years or older. Approximately 70% of individuals had an underlying medical condition making them high-risk for severe outcomes for COVID-19. VE was 52.8% [95% confidence interval (CI) 34.8%, 65.8%] against COVID-19-related hospitalization and 39.4% (35.0%, 43.5%) against medically-attended COVID-19 over a median follow-up of 55 (interquartile range 32-77) days in an interim analysis. The VE was sustained throughout the entire study period and shown to be 45.2% (37.7%, 51.8%) against COVID-19-related hospitalizations and 33.1% (30.6-35.4%) against medically-attended COVID-19 over a median follow-up of 127 (interquartile range 84-173) days.
CONCLUSION: The mRNA-1273 KP.2 vaccine demonstrated significant incremental effectiveness in preventing hospitalization with COVID-19 and medically-attended COVID-19 in adults during the 2024-2025 season to date. The VE was sustained with longer median follow up time. These findings support ongoing vaccination efforts to mitigate the public health impact of COVID-19.
