Same-Day COVID-19, Influenza Vaccination Does Not Increase Adverse Events

A target trial emulation published in the Annals of Internal Medicine found that giving the COVID-19 and influenza vaccines on the same day was not associated with an increased 90-day risk of serious or clinically meaningful adverse events compared with receiving the influenza vaccine alone. The study, conducted using nationwide electronic health records from the US Department of Veterans Affairs (VA), evaluated coadministration across 3 updated COVID-19 vaccine formulation periods: bivalent, XBB-adapted, and KP-adapted.¹

Study Design and Population

Investigators used a target trial emulation framework to ask whether, among adults presenting for routine vaccination at VA primary care clinics, same-day coadministration of a COVID-19 vaccine with an influenza vaccine—compared with influenza vaccination alone—affected the 90-day risk for 46 prespecified adverse events. The study drew from a cohort of 12,344,082 VA patients who attended a primary care visit between September 1, 2022, and August 26, 2025, when a seasonal influenza vaccine was administered. After exclusions, including recent vaccination, recent positive SARS-CoV-2 test, hospice care, or recent hospitalization or emergency department visit, the final analytic cohort totaled 2,518,329 participants.¹

Of those, 705,124 received a COVID-19 vaccine on the same day as their influenza vaccine and were classified into the coadministration group, and 1,813,205 received only the influenza vaccine. Participants were followed for 90 days from the day after vaccination, with influenza-only patients censored if they later received a COVID-19 vaccine during follow-up. The 46 outcomes were drawn from the Brighton Collaboration Adverse Events of Special Interest framework, Vaccine Adverse Event Reporting System signals, and the broader COVID-19 vaccine safety literature and were classified into 3 severity tiers: tier 1 (serious or life-threatening events), tier 2 (clinically significant events), and tier 3 (less severe or self-limiting events). Baseline inverse probability of treatment weighting was used to balance the 2 groups, an active-comparator design intended to reduce healthy vaccinee bias.¹

No Increased Risk Across Severity Tiers

Compared with influenza vaccination alone, coadministration was not associated with increased risk for any of the 3 composite severity outcomes. The standardized 90-day risk for the tier 1 composite was 705.41 per 100,000 in the coadministration group versus 682.73 per 100,000 in the influenza-only group (risk ratio [RR], 1.03 [95% CI, 0.99-1.09]). Tier 2 composite risk was 1,603.92 per 100,000 in the coadministration group versus 1,616.50 per 100,000 in the influenza-only group (RR, 0.99 [CI, 0.96-1.03]). Tier 3 composite risk was 2,244.75 per 100,000 in the coadministration group versus 2,277.28 per 100,000 in the influenza-only group (RR, 0.99 [CI, 0.96-1.02]).¹

Across the 46 individual outcomes, no tier 1 or tier 2 outcome reached statistical significance. Two tier 3 outcomes showed nominal significance in opposite directions—syncope (RR, 1.09 [CI, 1.02-1.17]) and tinnitus (RR, 0.95 [CI, 0.92-0.99])—but neither remained significant after Bonferroni correction for multiple comparisons within severity tiers.¹

Risks for myocarditis, a focus of prior COVID-19 vaccine safety surveillance, were low in both groups, with a risk difference of 1.11 per 100,000 (CI, −0.87 to 5.26) that included the null. When the analysis was stratified by vaccine period, no individual outcome or composite tier showed a statistically significant increase in risk in the bivalent, XBB-adapted, or KP-adapted era.¹

The authors acknowledged several limitations, including that the VA population is predominantly older, white, and male, which may limit generalizability, and that residual confounding cannot be fully excluded despite extensive covariate adjustment. Strengths included the target trial emulation framework, the active-comparator design intended to mitigate healthy vaccinee bias, and negative outcome controls that were consistent with the absence of specific measured biases. The authors concluded that 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."¹

Findings Align With Existing Federal Guidance

The new data build on long-standing CDC guidance that flu and COVID-19 vaccines can be administered at the same visit if a patient is eligible for both and the timing is appropriate. The agency notes that coadministration, or giving more than one vaccine during a single visit, is common clinical practice and that there is no recommended waiting time between a flu vaccine and a COVID-19 vaccine. When given with a needle at the same visit, vaccines should be administered at separate injection sites at least 1 inch apart.²

The CDC also points to prior research showing that patients who received a flu vaccine and a COVID-19 monovalent vaccine at the same time were slightly more likely to experience reactions such as fatigue, headache, and muscle ache than those who received the COVID-19 vaccine alone, though those reactions were generally mild and resolved quickly.²

Counseling Patients on Adverse Effects

For pharmacists administering both vaccines, patient counseling on expected adverse effects remains an important part of the visit. The study authors noted that they did not capture short-term reactions such as transient fever or injection-site pain that do not generate a clinical encounter, so milder, self-limited reactions may be more common in practice than the tier 3 findings alone suggest.¹

According to UC Davis Health, the most common adverse effects of a COVID-19 vaccine are a sore arm and sometimes fever, chills, tiredness, and headaches lasting a day or two, and common flu shot adverse effects include soreness, redness, or swelling at the injection site, along with a minor headache, fever, nausea, muscle aches, and fatigue. Patients who are not comfortable receiving both vaccines at once may also choose to space them out, as there is no recommended waiting period between the 2.^2,3

With flu and COVID-19 symptoms often overlapping, pharmacists may also field questions from patients trying to distinguish between the two illnesses. UC Davis Health notes that COVID-19 can cause diarrhea across all age groups, while diarrhea associated with flu is typically limited to children, and that changes in or loss of taste and smell are more common with COVID-19.³

REFERENCES

1. Xie Y, Choi T, Al-Aly Z. Adverse Events After Same-Day COVID-19 and Influenza Vaccination Versus Influenza Vaccination Alone: A Target Trial Emulation. Ann Intern Med. Published online June 30, 2026. doi:10.7326/ANNALS-26-00217

2. Centers for Disease Control and Prevention. Getting a flu vaccine and other recommended vaccines at the same time. CDC. Updated September 17, 2024. Accessed June 30, 2026. https://www.cdc.gov/flu/vaccines/coadministration.html

3. UC Davis Health. COVID and flu: symptoms, vaccine side effects and more. Cultivating Health. November 3, 2023. Updated October 28, 2024. Accessed June 30, 2026. https://health.ucdavis.edu/blog/cultivating-health/flu-and-covid-symptoms-vaccine-side-effects-and-more/2023/11