A large observational study using US healthcare claims and electronic health record data suggests that Moderna’s updated 2024-25 COVID vaccine was 39% effective at preventing medically attended illness among adults and 53% effective against hospitalization, particularly those at high risk for severe disease.
The study, led by scientists from the vaccine manufacturer and published late last week in Infectious Diseases and Therapy, analyzed outcomes among 596,248 adults who received the updated mRNA-1273 vaccine, which targeted the Omicron KP.2 variant, from August 2024 to April 2025. Vaccinated people were matched 1:1 with unvaccinated counterparts.
Overall, vaccine effectiveness (VE) against COVID-related hospitalization was estimated at 52.8% over a median follow-up of 55 days. Protection against COVID-related illness requiring medical attention was 39.4% over the same period. During the extended follow-up period, VE against hospitalization declined somewhat but remained significant, at 45.2%. VE for COVID cases that required medical attention was 33.1% during the extended timeframe (a median of 127 days, or about 4 months).
The mean age of the study participants was 63 years, and roughly 70% had underlying medical conditions such as asthma, cancer, diabetes, and chronic lung disease, that put them at high risk for severe outcomes. “Protection was consistently observed across subgroups, including older adults and those with other specific underlying medical conditions that may increase the risk of severe COVID-19,” write the authors.
Additive protection of yearly vaccination
The researchers note that because more than 70% of individuals in the study had received a 2023-24 mRNA-1273 vaccine, the findings also highlight the incremental protection of the 2024-25 vaccine against severe illness and hospitalization.
“As COVID-19 vaccination uptake remains low, it is imperative to communicate the additive protection COVID-19 vaccine provide [sic] year after year to reinforce confidence in vaccination among clinicians and the general population,” they write.
The study had some limitations. Because this was an observational study (and participants weren’t randomly assigned to be vaccinated), differences between the vaccinated and unvaccinated cohorts may have influenced the results.
For example, vaccinated people may have had better health overall and/or engaged in healthier behaviors, which lowered their risk of severe illness and hospitalization. The findings also relied on data from people who were engaged in the health care system, so people with limited access to health care may have been underrepresented.
To address these confounding factors, the researchers used multiple analytic approaches and closely matched vaccinated and unvaccinated adults on key characteristics, including age, sex, race, geographic region, prior vaccination status, and previous engagement with the health care system.
“The updated 2024–2025 mRNA-1273 KP.2 vaccine demonstrated substantial and incremental protection against hospitalization and medically-attended COVID-19 during the 2024/2025 respiratory virus season in the US,” conclude the authors. “These findings support continued annual vaccination efforts to reduce the burden of COVID-19, particularly among older adults and high-risk populations.”
