To evaluate the safety of same-day administration of updated COVID-19 and seasonal influenza vaccines compared to influenza vaccination alone.
Approach:
Study Design: A large target trial emulation was conducted within the U.S. Department of Veterans Affairs health care system.
Population: More than 2.5 million adults who received seasonal influenza vaccination between September 2022 and August 2025, including over 700,000 who received a COVID-19 vaccine on the same day.
Adverse Events Assessment: Adverse events were assessed over 90 days across three updated COVID-19 vaccine formulation periods: bivalent, XBB-adapted, and KP-adapted vaccines.
Key Findings:
No increased 90-day risks of serious, clinically significant, or self-limiting adverse events were found with same-day vaccination.
Risks for all prespecified composite outcome categories were similar between participants who received both vaccines and those who received only the influenza vaccine.
None of the 46 prespecified adverse events showed a statistically significant increase in risk after adjustment for multiple comparisons.
Interpretation:
The findings provide contemporary comparative safety evidence relevant to ongoing policy discussions about the safety of periodically updated COVID-19 vaccines.
Limitations:
The Veterans Affairs population was predominantly older, White, and male, which may limit generalizability.
Possibility of residual confounding despite extensive adjustment for baseline characteristics.
Rare adverse events could not be definitively excluded due to wide confidence intervals.
Transient reactions that did not result in clinical encounters were not captured.
Conclusion:
Same-day coadministration of COVID-19 and influenza vaccines was not associated with an increased risk for adverse events in three updated-formulation periods.
