Same-day administration of updated COVID-19 and seasonal influenza vaccines was not associated with increased 90-day risks of serious, clinically significant, or self-limiting adverse events compared with influenza vaccination alone, according to a large target trial emulation conducted in the U.S. Department of Veterans Affairs health care system.
Researchers evaluated more than 2.5 million adults who received seasonal influenza vaccination between September 2022 and August 2025, including more than 700,000 who received a COVID-19 vaccine on the same day. Adverse events were assessed over 90 days across three updated COVID-19 vaccine formulation periods: bivalent, XBB-adapted, and KP-adapted vaccines.
Risks for all three prespecified composite outcome categories, including serious or life-threatening events, clinically significant events, and less severe or self-limiting events, were similar between participants who received both vaccines on the same day and those who received an influenza vaccine alone. None of the 46 prespecified adverse events demonstrated a statistically significant increase in risk after adjustment for multiple comparisons.
Syncope and tinnitus showed nominal differences before correction for multiple testing, but neither remained statistically significant after adjustment.
Results were consistent across the bivalent, XBB-adapted, and KP-adapted vaccine periods, and multiple sensitivity analyses supported the primary findings.
“The findings provide contemporary comparative safety evidence relevant to ongoing policy discussions about the safety of periodically updated COVID-19 vaccines,” the authors wrote.
The investigators noted that the Veterans Affairs population was predominantly older, White, and male, which may limit generalizability. They also acknowledged the possibility of residual confounding despite extensive adjustment for baseline characteristics and stated that rare adverse events could not be definitively excluded because of wide confidence intervals. Transient reactions that did not result in clinical encounters, such as fever or injection-site pain, were not captured.
“Same-day coadministration of COVID-19 and influenza vaccines was not associated with an increased risk for adverse events in 3 updated-formulation periods,” the authors wrote. “The findings support the short-term safety of coadministration in older adults and may help inform ongoing vaccine policy discussions and individual risk-benefit assessments.”
The study was funded by the U.S. Department of Veterans Affairs. Disclosure forms are available with the article online.
Source: Annals of Internal Medicine
