Department of Research & Evaluation News

A large multisite study found that bivalent mRNA COVID-19 vaccination, flu vaccination, and same-day administration of both vaccines were not associated with an increased risk of first-ever ischemic stroke.

“This study found no evidence of an increased risk of ischemic stroke following bivalent COVID-19 vaccination, influenza vaccination, or receiving both vaccines on the same day,” said lead author Stanley Xu, PhD, a researcher with the Kaiser Permanente Southern California Department of Research & Evaluation. “Using data from more than 6.8 million individuals across multiple U.S. health systems and analyzing 6,510 first-ever ischemic stroke cases, we were able to thoroughly investigate an earlier concern and found consistent evidence supporting the safety of these vaccines with respect to ischemic stroke.”

The study was published online in Vaccine in October 2026.

The results address concerns raised by an earlier safety signal detected among older adults during the 2022–2023 respiratory virus season, study authors said.

The study is notable for simultaneously evaluating bivalent COVID-19 vaccination, influenza vaccination, and same-day administration of both vaccines within a single analysis, while focusing specifically on first-ever ischemic stroke. It also included analyses across different age groups, vaccine types, and time periods after vaccination.

Study addresses earlier safety signal

The study, led by researchers from Kaiser Permanente Southern California and collaborators across the U.S. Vaccine Safety Datalink, examined whether people were more likely to experience this type of stroke during the 1–21 days and 1–42 days after vaccination. Ischemic stroke occurs when blood flow to part of the brain is blocked, making it the most common type of stroke.

Researchers investigated the question after a preliminary, unconfirmed signal identified in late 2022 suggested a possible increase in the risk of ischemic events, including ischemic stroke or transient ischemic attack (TIA), among adults aged 65 years and older who received a Pfizer-BioNTech bivalent COVID-19 booster, particularly when administered alongside certain influenza vaccines. The signal prompted vaccine safety experts to investigate whether the association reflected a true safety concern.

To conduct the study, the investigators used a self-controlled case series design, a rigorous method that compares predefined post-vaccination risk periods with other times in the same person. Because each person serves as their own control, the approach helps account for underlying factors that do not change over time, including existing health risks that could influence stroke likelihood.

Large Vaccine Safety Datalink analysis

The study population included individuals aged 12 years and older from 8 integrated health care systems participating in the Vaccine Safety Datalink. Among these participants, researchers identified 6,510 people who experienced a first-ever ischemic stroke during the 2022–2023 respiratory virus season and included them in the analysis.

Among people who received the Pfizer-BioNTech bivalent COVID-19 vaccine, researchers found no increased risk of first-ever ischemic stroke during either the 1–21-day or 1–42-day period after vaccination. Similar findings were observed for Moderna’s bivalent vaccine.

Results consistent across groups

Investigators also found no increased risk after influenza vaccination alone. In addition, receiving a bivalent COVID-19 vaccine and an influenza vaccine on the same day was not associated with a higher risk of ischemic stroke. The findings remained consistent across both the 1–21-day and 1–42-day post-vaccination risk windows.

The pattern held among adults ages 65 and older, younger individuals ages 12 to 64, and people with and without a documented history of SARS-CoV-2 infection. Additional analyses examining broader ischemic events, including TIA, also found no increased risk.

Findings support existing evidence

The findings add to existing evidence supporting the safety of bivalent COVID-19 vaccination, influenza vaccination, and same-day flu vaccination with respect to ischemic stroke, while underscoring the importance of ongoing monitoring when preliminary safety signals emerge.

The research team plans to apply the same analytic approach to newer COVID-19 vaccine formulations, including the updated monovalent XBB.1.5 vaccine used during the 2023–2024 season, while continuing to evaluate vaccine safety alongside influenza vaccination.

Authors in addition to Dr. Xu include Lina S. Sy, MPH; Vennis Hong, MPH; Sungching C. Glenn, MS; Sunhea Kim, MPH; Denison S. Ryan, MPH; Julia E. Tubert, MPH; Paulina Tong, MPH; Bruno J. Lewin, MD; Hung Fu Tseng, MPH, PhD; and Lei Qian, PhD, of the Department of Research & Evaluation; Alexandra Carbayo, MD; Cameron Davis, DO; and Navdeep S. Sangha, MD, of the Department of Neurology, Kaiser Permanente Southern California; Paddy Farrington, PhD, of The Open University, United Kingdom; Edward A. Belongia, MD, and Maria E. Sundaram, PhD, MSPH, of Marshfield Clinic Research Institute; Jennifer C. Nelson, PhD, of Kaiser Permanente Washington Health Research Institute; Matthew F. Daley, MD, of Kaiser Permanente Colorado Institute for Health Research; Nicola P. Klein, MD, PhD, and Bruce Fireman, MA, of Kaiser Permanente Northern California; Jacob Haapala, MPH, of HealthPartners Institute; Laura P. Hurley, MD, MPH, of Denver Health; Stephanie A. Irving, MHS, of Kaiser Permanente Northwest Center for Health Research; Noelle M. Cocoros, MPH, DSc, of Harvard Pilgrim Health Care Institute; and Eric S. Weintraub, MPH, and Jonathan Duffy, MD, MPH, of the Centers for Disease Control and Prevention Immunization Safety Office.