Objective:

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.

Sources:

• Annals of Internal Medicine