Concomitant COVID-19 and influenza vaccination not linked to increased adverse events

1. In this target trial emulation, same-day administration of COVID-19 and influenza vaccines was not associated with an increased risk of adverse events.

2. No differences in adverse event risk were observed across the bivalent, XBB-adapted, and KP-adapted COVID-19 vaccine formulations.

Evidence Rating Level: 2 (Good)

Study Rundown: The evolution of SARS-CoV-2 has led to COVID-19 vaccination programs adopting periodic, variant-updated formulations, similar to seasonal influenza vaccines. This study evaluated the safety of co-administering COVID-19 and influenza vaccines during the same primary care visit compared with administering the influenza vaccine alone. Between 2022 and 2025, more than 700,000 individuals received both an influenza vaccine and one of three COVID-19 vaccines (bivalent, XBB-adapted, or KP-adapted), while 1.8 million received only the influenza vaccine. Standardized 90-day risks of serious or life-threatening adverse events and clinically significant events were comparable between groups, and risks of less severe or self-limiting events were nearly identical. Of the 46 individual adverse events examined, only syncope and tinnitus reached statistical significance, with effect estimates in opposite directions. COVID-19 vaccine formulation was not associated with an increased risk for any composite outcome, and sensitivity analyses yielded consistent findings. Although generalizability is limited by the predominantly older, White, male veteran population and the potential for residual confounding and outcome misclassification, these findings support the safety of same-day COVID-19 and influenza vaccination. This evidence may help inform discussions on the risks and benefits of co-administration and support public health vaccination strategies.

Click to read this study in AIM

Relevant Reading: Safety of JN.1-Updated mRNA COVID-19 Vaccines

In-Depth [prospective cohort]: This target trial emulation evaluated the 90-day safety of concomitant COVID-19 and influenza vaccination compared with influenza vaccination alone in primary care settings affiliated with the US Department of Veterans Affairs (VA). Using VA electronic health records, adults who received a seasonal influenza vaccine during a primary care visit between September 1, 2022, and August 26, 2025, were eligible. Participants could contribute up to three observations corresponding to the availability of the bivalent, XBB-adapted, and KP-adapted COVID-19 vaccines. Individuals were excluded for factors including recent COVID-19 or influenza vaccination, recent SARS-CoV-2 infection, end-of-life care, recent hospitalization or emergency department visits, or limited engagement with VA primary care. Adverse events were assessed over 90 days and classified into three severity tiers: serious or life-threatening (tier 1), clinically significant (tier 2), and less severe or self-limiting (tier 3). The study included 705,124 participants who received concomitant COVID-19 and influenza vaccines and 1,813,205 who received influenza vaccine alone. Compared with influenza vaccination alone, concomitant vaccination was not associated with increased risk of tier 1 (risk ratio [RR], 1.03; 95% confidence interval [CI], 0.99-1.09), tier 2 (RR, 0.99; 95% CI, 0.96-1.03), or tier 3 (RR, 0.99; 95% CI, 0.96-1.02) composite outcomes. No statistically significant differences were observed for any individual tier 1 or tier 2 adverse event. Although syncope (RR, 1.09; 95% CI, 1.02-1.17) and tinnitus (RR, 0.95; 95% CI, 0.92-0.99) initially reached statistical significance, the associations were in opposite directions and were no longer significant after Bonferroni correction. Stratified analyses showed no increased risk with the bivalent, XBB-adapted, or KP-adapted COVID-19 vaccine formulations, and sensitivity analyses produced findings consistent with the primary analysis. Overall, the study provides strong evidence that concomitant administration of COVID-19 and influenza vaccines is not associated with an increased risk of adverse events compared with influenza vaccination alone.

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