- Both the SARS-CoV-2 virus and the vaccines to prevent it have evolved since 2020, but oft-cited vaccine safety data tend to come from the pandemic’s early vaccines.
- In a target trial emulation, getting a COVID and flu shot on the same day was not associated with an increased risk of adverse events versus getting a flu shot alone.
- Of note, myocarditis risks were small in both the coadministration and flu vaccine-only groups.
Getting a COVID and flu shot on the same day was not associated with an increased risk of adverse events, according to a target trial emulation using electronic health data from the VA.
Compared with influenza vaccination alone, coadministration of COVID and influenza vaccines was not associated with an increased risk for any of the three composite outcomes of serious or life-threatening, clinically significant, or less severe or self-limiting adverse events, reported Ziyad Al-Aly, MD, of Washington University in St. Louis, and colleagues in the Annals of Internal Medicine.
Of the 46 individual adverse events assessed, two less severe or self-limiting adverse events had “nominal statistical significance” with coadministration — a slightly higher risk of syncope (risk ratio [RR] 1.09, 95% CI 1.02-1.17) and a slightly lower risk for tinnitus (RR 0.95, 95% CI 0.92-0.99) — but no risks were statistically significant after correcting for multiple comparisons.
“Even in today’s world, where people have been exposed to multiple prior COVID-19 vaccines and their immune systems have been shaped by at least one COVID-19 infection, vaccines have a reassuring record of safety,” Al-Aly told MedPage Today. “We looked at 46 different outcomes — literally leaving no stone unturned — and we came up empty-handed.”
Both the SARS-CoV-2 virus and the vaccines to prevent it have evolved since 2020, Al-Aly noted, but oft-cited vaccine safety data tend to come from the pandemic’s early vaccines. The population’s immunity has shifted as well, he said, and the resulting hybrid immunity may change people’s susceptibility to vaccine adverse events.
To account for those shifts, the researchers included data from three COVID vaccine formulation eras between September 2022 and August 2025: bivalent vaccines, XBB-adapted vaccines, and KP-adapted vaccines.
“COVID severity has very clearly declined, but it’s still not an inconsequential nothing-burger,” Al-Aly cautioned. Particularly in older adults and those with comorbidities, he added, the findings reinforce that COVID vaccines’ risk-benefit balance still favors vaccination.
The researchers used VA electronic health data to run a target trial emulating randomization to either same-day coadministration of COVID and flu vaccines or flu vaccines alone. That active-comparator design matching two vaccinated groups reduced the potential effect of healthy-vaccinee bias, Al-Aly explained. The coadministration group included 705,124 people who received both vaccines on the same day, while 1,813,205 people received just a flu shot.
Mean patient age was 69.7 years in the coadministration group and 68.4 years in the flu vaccine-only group. The majority of both groups were male (92.7%), and white (72-78%). High-dose flu vaccines were given to 58.8% of the coadministration group and 51.1% of the flu vaccine-only group. Among the coadministration group, 60.4% received the Moderna vaccine, 39.2% received the Pfizer vaccine, and 0.46% received other vaccine formulations.
In each of the three vaccine eras, there was no significantly increased risks of any of the individual adverse events in the coadministration group compared with the flu vaccine-only group.
Of note, myocarditis risks were small in both the coadministration and flu vaccine-only groups, and confidence bounds of the difference were wide including the null, the authors pointed out (risk difference 1.11, 95% CI -0.87 to 5.26).
Study limitations included the VA’s predominantly older, male, and white population, which may limit the findings’ generalizability. The researchers didn’t measure short-term adverse events such as transient fever or injection site pain that may not have led to clinical encounters.
