Estimating the risk of transient ischemic attacks and non-hemorrhagic stroke following Spikevax bivalent compared to influenza vaccination in the US

Background: There is inconsistent evidence concerning a potential association between mRNA-based bivalent boosters and transient ischemic attacks (TIA) and non-hemorrhagic (NH) stroke among adults with concurrent influenza vaccinations, thus additional analyses estimating the risk of these two outcomes is warranted.

Objectives: To estimate the risk of TIA and NH stroke in the 1-21 and 22-42 days following concurrent vaccinations compared to influenza only vaccinations among adults ≥18 years.

Methods: This is a retrospective observational cohort study using closed medical and pharmacy claims from HealthVerity in the US from September 1, 2022 through May 1, 2023. Eligible vaccination episodes were identified among adults ≥18 years, with at least 1 year of continuous enrollment, and no evidence of TIA or NH stroke prior to the index vaccination. Vaccinations were identified via procedure and drug codes; concurrent vaccinations were defined as Spikevax bivalent and influenza vaccinations occurring within 0-14 days.

Propensity scores (PS) were calculated using inverse probability weighting to estimate the probability of receiving Spikevax bivalent conditional on measured baseline covariates. Cox proportional hazards regression was used to evaluate the relationship between vaccination and each outcome in the 1-21 and 22-42 days following index.

Results: In the TIA analysis, there were 545,509 and 5,179,120 adults with concurrent and influenza only vaccinations, respectively. In the PS-weighted models, there was no increased risk of TIA in the 1-21 or 22-42 days following concurrent vaccination compared to influenza vaccination alone (1-21 day weighted hazard ratio (wHR): 0.78, (95% CI 0.65, 0.94), 22-42 day wHR: 0.82, (95% CI: 0.68, 1.00)).

In the NH stroke analysis, among 542,336 and 5,132,499 adults with concurrent and influenza only vaccinations, no increased risk of NH stroke was observed in the 1-21 or 22-42 days following concurrent vaccination compared to influenza only vaccination (1-21 day wHR: 0.76, (0.58, 1.00), 22-42 day wHR: 0.71, (0.54, 0.93)). Additionally, analyses stratified by age (18-64 and ≥65 years) were consistent with the overall population.

Conclusions: No risk of TIA or NH stroke was observed in the 1-42 days following concurrent Spikevax bivalent and influenza vaccination compared to influenza vaccination alone among adults, providing further evidence of the safety of Spikevax bivalent with concurrently administered influenza vaccinations.