Background: 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 24 December 2024 and followed through 31 December 2024. 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, 465,073 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 57 (interquartile range: 33 to 78) 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. These findings support ongoing vaccination efforts to mitigate the public health impact of COVID–19.
### Competing Interest Statement
AW, AA, KJ, TL, and ZZ are employees and stockholders of Moderna, Inc. AB, TR, NZ, and MB are employees of Veradigm, which was contracted by Moderna and received fees for data management and statistical analyses.
### Funding Statement
This work was funded by Moderna Inc.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
This study leveraged electronic health record (EHR) data from the Veradigm Network EHR linked to administrative healthcare claims sourced from Komodo Health. The Veradigm Network EHR data used in our study has been de-identified prior to its use in this study. This study was conducted in accordance with the Declaration of Helsinki and relevant guidelines for observational studies. The research involved de-identified claims data and did not require direct patient involvement. Therefore, specific ethics approval and informed consent were not needed, as the data were anonymized and complied with patient privacy regulations. Access to the data was provided under agreements with the data provider, which ensured adherence to ethical standards, including the protection of patient confidentiality.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
Individual-level data reported in this study are not publicly shared. Upon request, and subject to review, Veradigm may provide the deidentified aggregate-level data that support the findings of this study. Deidentified data (including participant data as applicable) may be shared upon approval of an analysis proposal and a signed data access agreement. Individual-level data reported in this study are shared fully with regulatory agencies.