COVID-19 and Flu Vaccine Together: Large VA Study Finds No Increased 90-Day Safety Risk

Introduction

A large observational study published in the Annals of Internal Medicine examined whether receiving the COVID-19 vaccine and the seasonal influenza vaccine on the same day increases the risk of adverse health events within 90 days. The research is based on updated vaccine formulations used during recent seasons, including bivalent, XBB-adapted, and KP-adapted COVID-19 vaccines.

The findings are important for clinicians, public health decision makers, and patients because coadministration of vaccines is now commonly recommended to improve uptake and convenience. However, questions have remained about whether combining vaccines might increase short-term safety risks compared with receiving only the flu shot.

This blog provides a simplified summary of the study, its methods, results, and implications.

Study Overview

The research was conducted by using electronic health records from the U.S. Department of Veterans Affairs (VA), one of the largest integrated healthcare systems in the United States.

They compared two groups:

• People who received both COVID-19 and flu vaccines on the same day
• People who received only the flu vaccine

The study included more than 2.5 million vaccinated individuals and followed them for 90 days after vaccination.

Why This Study Was Done

Earlier COVID-19 vaccine safety studies focused on the initial vaccine rollout period and shorter follow-up times. Since then, several changes have occurred:

• New COVID-19 variants led to updated vaccine formulations
• Many people now have hybrid immunity from infection and vaccination
• Booster strategies and annual COVID-19 vaccination have become common

Because of these changes, earlier safety data may not fully represent current real-world conditions. The researchers aimed to update safety evidence using more recent vaccine versions and a large modern dataset.

How the Study Was Designed

This study used a method called target trial emulation. In simple terms, it tries to mimic a randomized clinical trial using real-world data.

Key design features included:

• A 90-day follow-up period after vaccination
• Active comparison between two vaccinated groups
• Adjustment for differences in age, health conditions, medications, and healthcare use
• Statistical weighting to reduce bias and balance groups

The study also accounted for people who later crossed over from flu-only vaccination to receiving a COVID-19 vaccine during follow-up.

Researchers evaluated 46 different possible adverse health outcomes. These were grouped into three severity categories:

• Tier 1: serious or life-threatening conditions
• Tier 2: clinically significant medical conditions
• Tier 3: milder or self-limiting conditions

Main Findings

Overall, the study found no meaningful increase in risk when COVID-19 and flu vaccines were given together.

Composite safety outcomes:

• Tier 1 (serious outcomes): no increase in risk
• Tier 2 (clinically significant outcomes): no increase in risk
• Tier 3 (mild outcomes): no meaningful difference

Risk ratios for all major categories were approximately 1.0, meaning no measurable difference between groups.

Individual Health Events

Out of 46 specific health outcomes:

• No serious or clinically significant conditions showed increased risk after coadministration
• Two mild outcomes showed small statistical signals:
  • Syncope (fainting) showed a slight increase
  • Tinnitus showed a slight decrease

However, after correcting for multiple statistical comparisons, these differences were not considered meaningful.

In practical terms, these small signals were interpreted as likely due to chance rather than a true vaccine effect.

Results Across Different Vaccine Periods

The study also analyzed results across three different COVID-19 vaccine eras:

• Bivalent vaccine period
• XBB-adapted vaccine period
• KP-adapted vaccine period

In each period, results were consistent:

• No increased risk in serious, moderate, or mild outcome categories
• No consistent safety concerns across time

This suggests that updated COVID-19 vaccine formulations do not change the safety profile of coadministration with influenza vaccines.

Key Interpretation

The researchers concluded that receiving both vaccines on the same day does not increase the risk of adverse health events within 90 days.

They also highlighted that:

• The absolute risk differences were very small
• No pattern of harm was observed across multiple disease categories
• Findings were consistent across multiple sensitivity analyses

Importantly, the study suggests that any apparent small differences in rare outcomes are likely due to statistical noise rather than true clinical risk.

Why These Findings Matter

Co-administering vaccines has several public health advantages:

• Improves vaccination rates by reducing clinic visits
• Simplifies logistics for healthcare systems
• Increases protection against both influenza and COVID-19 in a single visit

This study supports the idea that combining vaccines is not associated with short-term safety concerns in older adult populations, particularly in healthcare systems similar to the VA.

The findings also contribute to ongoing debates about vaccine safety in the context of updated COVID-19 boosters and evolving immunity patterns.

Study Limitations

While the study is large and methodologically strong, it has some limitations:

• The VA population is mostly older, male, and not fully representative of the general population
• Some mild side effects that do not require medical care were not captured
• Residual confounding is still possible despite statistical adjustments
• Rare outcomes may still have wide confidence intervals, meaning very small risks cannot be completely excluded

Strengths of the Study

Despite limitations, the study has several strengths:

• Very large sample size (over 2.5 million participants)
• Real-world nationwide healthcare data
• Active comparator design reducing bias
• Extensive adjustment for medical and demographic factors
• Evaluation across multiple vaccine eras
• Analysis of 46 different adverse outcomes

These features make it one of the most comprehensive modern evaluations of COVID-19 and flu vaccine coadministration safety.

Conclusion

This large real-world study found that receiving COVID-19 and influenza vaccines on the same day does not increase the risk of serious, moderate, or mild adverse health outcomes within 90 days.

The results remained consistent across different COVID-19 vaccine formulations and multiple sensitivity analyses. Only very small and inconsistent signals were observed for minor outcomes, which did not remain significant after statistical correction.

Overall, the evidence supports the short-term safety of coadministering COVID-19 and influenza vaccines in contemporary healthcare settings.

Source: Yan Xie, Taeyoung Choi, Ziyad Al-Aly. Adverse Events After Same-Day COVID-19 and Influenza Vaccination Versus Influenza Vaccination Alone: A Target Trial Emulation. Ann Intern Med. [Epub 30 June 2026]. doi:10.7326/ANNALS-26-00217

Disclaimer

This article is a written educational summary based on a peer-reviewed publication and is intended for informational purposes only. It does not provide medical advice, diagnosis, or treatment recommendations. Clinical decisions should always be made in consultation with qualified healthcare professionals. The original study may include additional methodological details, statistical analyses, and limitations not fully captured here.