On Nov. 11, 2026, Moderna announced the publication of results from a large real-world study evaluating the comparative effectiveness of mNEXSPIKE® (COVID-19 Vaccine, mRNA) and Comirnaty® (COVID-19 Vaccine, mRNA) among U.S. Veterans aged 65 years and older during the 2025-2026 respiratory virus season. The analysis, published in JAMA Network Open, included 294,499 matched participants in the U.S. Veterans Health Administration (VHA).

The study’s primary outcome was medically attended COVID-19, including hospitalization, emergency room visits, urgent care, outpatient visits, and antiviral treatment. mNEXSPIKE was associated with 35.9% relative vaccine effectiveness against medically attended COVID-19 compared with Comirnaty (95% CI: 20.4%-49.7%). The study found that vaccination with mNEXSPIKE was associated with a 47.0% relative vaccine effectiveness against COVID-19-associated hospitalization compared with Comirnaty (95% CI: 5.4%-74.8%), and point estimates consistently favored mNEXSPIKE across all individual components of medically attended COVID-19.

An exploratory analysis also evaluated hospitalization involving a major adverse cardiovascular event (MACE), including myocardial infarction, stroke or heart failure. mNEXSPIKE was associated with 39.3% relative vaccine effectiveness for MACE hospitalization compared with Comirnaty (95% CI: 11.8%-57.0%). COVID-19 has been associated with worsening of underlying chronic conditions, including cardiovascular disease. The data highlight the importance of understanding the potential broader health impact of COVID-19 prevention in older adults, beyond the acute respiratory illness.

The retrospective, active-comparator matched cohort study included VHA-enrolled veterans aged 65 years and older who received an LP.8.1-formulated mNEXSPIKE or Comirnaty vaccine between August 27, 2025, and January 31, 2026. Participants were followed for up to 150 days or through May 1, 2026. The analysis matched participants by home county and calendar week of vaccination and used inverse probability of treatment weighting to further reduce potential confounding.

As an observational real-world analysis, the study is subject to residual confounding, including differences in testing behavior, undocumented prior infection and vaccine availability. The predominantly older, male VHA population may limit generalizability to broader populations. Findings are associative and do not establish causality. Despite these potential limitations, the study provides important real-world comparative evidence on COVID-19 vaccine effectiveness in older adults, a population that remains at increased risk of severe COVID-19 and its complications.

The study was supported by Moderna, which contributed to the study design, data interpretation, manuscript preparation, review and approval, and the decision to submit for publication. Moderna did not conduct the study or collect, manage or analyze the data.