Key Takeaways
- In 294,499 matched U.S. veterans 65 and older, mNEXSPIKE was linked to 36% fewer COVID medical visits than Pfizer's Comirnaty.
- COVID hospitalizations were 47% lower with mNEXSPIKE, though that estimate has a very wide confidence interval.
- The study was observational and supported by Moderna, so it shows an association, not proof one shot is better.
A real-world comparison of two COVID vaccines
Moderna's newer COVID-19 vaccine, mNEXSPIKE, was associated with a lower risk of medically attended COVID-19 than Pfizer-BioNTech's Comirnaty in a large observational study of older U.S. veterans. The analysis, reported as published in JAMA Network Open, included 294,499 matched veterans aged 65 and older receiving care through the Veterans Health Administration during the 2025–26 respiratory virus season. Unlike a randomized clinical trial, the study compared outcomes among people who received the two vaccines in routine medical practice.
What the researchers found
Compared with Comirnaty, mNEXSPIKE was associated with a 35.9% lower relative risk of medically attended COVID-19. The study's definition of medically attended COVID-19 included hospitalizations, emergency department visits, urgent care, outpatient visits and antiviral treatment. The researchers also reported a 47% lower relative risk of COVID-19 hospitalization among mNEXSPIKE recipients. However, the hospitalization estimate had a wide confidence interval, ranging from a 5.4% to a 74.8% relative risk reduction. This indicates substantial uncertainty about the size of the observed difference. These percentages describe relative differences between groups, not the absolute probability that an individual will become ill or require hospitalization.
Who received the vaccines?
The analysis compared recipients of LP.8.1-formulated mNEXSPIKE, also known as mRNA-1283, with recipients of Comirnaty. Vaccinations occurred between August 27, 2025, and January 31, 2026, with participants followed for up to 150 days. An exploratory analysis also suggested a 39.3% lower risk of hospitalization involving a major cardiovascular event, such as a heart attack or stroke, among mNEXSPIKE recipients. That secondary finding should be interpreted cautiously. It does not establish that mNEXSPIKE prevents cardiovascular events more effectively than Comirnaty.
Why the findings need caution
The study was observational, meaning researchers examined outcomes after vaccination rather than randomly assigning participants to receive one vaccine or the other. Even with statistical matching, differences between the groups could have influenced the results. Potential limitations included differences in COVID-19 testing behaviour, previously undocumented infections and vaccine availability. The study population also consisted primarily of older men receiving care through the U.S. veterans' health system. The findings may not apply equally to women, younger adults or other populations. The study was supported by Moderna, which participated in study design, interpretation of findings, manuscript preparation and the decision to submit the research for publication. According to the reported disclosures, Moderna did not conduct the study or collect, manage or analyze the underlying data. This industry involvement is important context when evaluating the findings.
The Twikup Take
The study suggests that Moderna's newer mNEXSPIKE vaccine may offer an advantage over Pfizer-BioNTech's Comirnaty in reducing medically attended COVID-19 among adults aged 65 and older. The large sample makes the findings noteworthy, but the observational design means the results cannot establish that one vaccine is definitively superior. The reported hospitalization difference is potentially important, although its wide confidence interval leaves uncertainty about the magnitude of the benefit. Further independent research would help determine whether the observed differences persist across broader populations and future respiratory virus seasons. For now, the findings add evidence to the comparison between updated COVID-19 vaccines without settling which product is best for every individual. This study looked at a specific group — U.S. veterans aged 65 and older — and compared two vaccines in a real-world setting, not a controlled trial. It does not change general vaccination guidance, and anyone deciding on a COVID vaccine should talk to their own doctor or pharmacist. Image: Illustrative image.