Stroke Risk After COVID-19 Bivalent Vaccination Among US Older Adults

Abstract

Importance: In January 2023, the US Centers for Disease Control and Prevention and the US Food and Drug Administration noted a safety concern for ischemic stroke among adults aged 65 years or older who received the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine.

Objective: To evaluate stroke risk after administration of (1) either brand of the COVID-19 bivalent vaccine, (2) either brand of the COVID-19 bivalent plus a high-dose or adjuvanted influenza vaccine on the same day (concomitant administration), and (3) a high-dose or adjuvanted influenza vaccine.

Design, setting, and participants: Self-controlled case series including 11 001 Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine (among 5 397 278 vaccinated individuals). The study period was August 31, 2022, through February 4, 2023.

Exposures: Receipt of (1) either brand of the COVID-19 bivalent vaccine (primary) or (2) a high-dose or adjuvanted influenza vaccine (secondary).

Main outcomes and measures: Stroke risk (nonhemorrhagic stroke, transient ischemic attack, combined outcome of nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day risk window after vaccination vs the 43- to 90-day control window.

Results: There were 5 397 278 Medicare beneficiaries who received either brand of the COVID-19 bivalent vaccine (median age, 74 years [IQR, 70-80 years]; 56% were women). Among the 11 001 beneficiaries who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there were no statistically significant associations between either brand of the COVID-19 bivalent vaccine and the outcomes of nonhemorrhagic stroke, transient ischemic attack, nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke during the 1- to 21-day or 22- to 42-day risk window vs the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12). Among the 4596 beneficiaries who experienced stroke after concomitant administration of either brand of the COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window for the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine (IRR, 1.20 [95% CI, 1.01-1.42]; risk difference/100 000 doses, 3.13 [95% CI, 0.05-6.22]) and a statistically significant association between vaccination and transient ischemic attack during the 1- to 21-day risk window for the Moderna mRNA-1273.222 COVID-19 bivalent vaccine (IRR, 1.35 [95% CI, 1.06-1.74]; risk difference/100 000 doses, 3.33 [95% CI, 0.46-6.20]). Among the 21 345 beneficiaries who experienced stroke after administration of a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window (IRR, 1.09 [95% CI, 1.02-1.17]; risk difference/100 000 doses, 1.65 [95% CI, 0.43-2.87]).

Conclusions and relevance: Among Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there was no evidence of a significantly elevated risk for stroke during the days immediately after vaccination.

Figure 1.. Cohort Summary for the Primary Analysis

AESI indicates adverse event of special interest; FFS, fee-for-service. ^aFor those who experienced a nonhemorrhagic stroke, the study period spans from August 31, 2022, to January 18, 2023, and the vaccine cutoff date (90 days prior to study end) was October 20, 2022. For those who experienced a transient ischemic attack, the study period spans from August 31, 2022, to February 4, 2023, and the vaccine cutoff date was November 6, 2022. For those who experienced a nonhemorrhagic stroke or a transient ischemic attack, the study period spans from August 31, 2022, to January 18, 2023, and the vaccine cutoff date was October 20, 2022. For those who experienced a hemorrhagic stroke, the study period spans from August 31, 2022, to January 12, 2023, and the vaccine cutoff date was October 14, 2022. ^bA beneficiary may have contributed to multiple outcome cohorts; therefore, the sum of the outcome case populations is greater than the number of unique beneficiaries who experienced an AESI during the observation period. ^cThe outcome-specific International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, exclusion codes appear in eTable 5 in Supplement 1.

Figure 2.. Risk of Stroke in the Primary Analysis and in the Subgroup Analysis by COVID-19 Bivalent Vaccine Brand

IRR indicates incidence rate ratio. The IRRs were obtained using conditional Poisson regression. The primary analysis included Medicare beneficiaries who received either brand of the COVID-19 bivalent vaccine. The subgroup analysis included Medicare beneficiaries who received either brand of the COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine on the same day (concomitant vaccination).

Figure 3.. Risk of Stroke by Age Subgroup and Seasonality-Adjusted Analyses for Those Who Received the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 Bivalent Vaccine

IRR indicates incidence rate ratio. The IRRs were obtained using conditional Poisson regression.

Figure 4.. Risk of Stroke by Age Subgroup and Seasonality-Adjusted Analyses for Those Who Received the Moderna mRNA-1273.222 COVID-19 Bivalent Vaccine

IRR indicates incidence rate ratio. The IRRs were obtained using conditional Poisson regression.