Same-day vaccination showed no safety increase

Same-day COVID-19 and influenza vaccination did not increase 90-day adverse event risk versus influenza vaccination alone.
*Target trial emulation cohort study; Level 3.

Citation

Xie Y, Choi T, Al-Aly Z. Adverse Events After Same-Day COVID-19 and Influenza Vaccination Versus Influenza Vaccination Alone. Ann Intern Med. 2026;179:1073-1084. doi:10.7326/ANNALS-26-00217

Background

Earlier COVID-19 vaccine safety data may not fully apply to newer vaccine formulations and populations with more prior infection or vaccination. This study assessed whether adding updated COVID-19 vaccination to a same-day influenza vaccine visit increased short-term harms.

Patients

2,518,329 U.S. Veterans Affairs primary care vaccination visits. Exclusions included recent COVID-19 or influenza vaccination, recent positive COVID-19 test, end-of-life care, recent hospital or emergency visit, and sites with low coadministration use.

Intervention

Same-day COVID-19 and seasonal influenza vaccines.

Control

Seasonal influenza vaccine alone.

Outcome

Forty-six prespecified adverse events grouped as serious or life-threatening, clinically significant, or less severe/self-limiting.

Follow-up Period

90 days after vaccination.

Results

Relative comparisons showed no increased composite risk: serious/life-threatening risk ratio 1.03 (95% confidence interval 0.99 to 1.09), clinically significant 0.99 (95% confidence interval 0.96 to 1.03), and less severe/self-limiting 0.99 (95% confidence interval 0.96 to 1.02).

Outcome Influenza alone risk per 100,000 Same-day vaccination risk per 100,000
Serious/life-threatening 682.73 (95% confidence interval 667.25 to 698.66) 705.41 (95% confidence interval 675.71 to 739.07)
Clinically significant 1616.50 (95% confidence interval 1590.29 to 1643.93) 1603.92 (95% confidence interval 1559.13 to 1654.74)
Less severe/self-limiting 2277.28 (95% confidence interval 2247.94 to 2306.18) 2244.75 (95% confidence interval 2184.39 to 2313.21)

Analyses were per-protocol. Two mild-event signals, fainting and tinnitus, were nominal before correction but not significant after accounting for many comparisons.

Limitations

Veterans Affairs patients were mostly older, White, and male, limiting generalizability. Unmeasured confounding and missed care outside Veterans Affairs remain possible. Rare events in younger people, including myocarditis, could not be excluded confidently.

Funding

U.S. Department of Veterans Affairs; no reported sponsor analytic role.

Clinical Application

Offer same-day COVID-19 and influenza vaccination when indicated; this large study supports short-term safety in older Veterans Affairs patients.