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

Abstract

ImportanceIn 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.ObjectiveTo 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 ParticipantsSelf-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.ExposuresReceipt of (1) either brand of the COVID-19 bivalent vaccine (primary) or (2) a high-dose or adjuvanted influenza vaccine (secondary).Main Outcomes and MeasuresStroke 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.ResultsThere 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 RelevanceAmong 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.

Stroke After Influenza Vaccines in Older Adults in the US, 2016 to 2019

“…In this SCCS study, the risk of nonhemorrhagic stroke (NHS), transient ischemic attack (TIA), NHS and/or TIA (NHS/TIA), and hemorrhagic stroke (HS) following exposure to a high-dose or adjuvanted influenza vaccine was evaluated among persons 65 years or older (primary analysis) and by age subgroup (65-74, 75-84, and ≥85 years). 1 , 2 , 3 Fixed risk windows (1-21 and 22-42 days) were compared with a control window (43-90 days). For each influenza season, the study period began on the first Sunday of August and ended 1 day before the start of the subsequent season.…”

“…The US Food and Drug Administration (FDA) investigated stroke risk following COVID-19 bivalent and influenza vaccines among Medicare beneficiaries 65 years or older in 2022 and 2023 . The self-controlled case series (SCCS) study found no consistent evidence of stroke risk in the days following COVID-19 bivalent vaccination.…”

Ischemic Stroke After Bivalent COVID-19 Vaccination: Self-Controlled Case Series Study

“…Another SCCS study conducted in Israel also did not find an increased risk of ischemic stroke following monovalent or bivalent mRNA COVID-19 vaccine boosters in at-risk populations [ 15 ]. A study of Medicare beneficiaries aged 65 years or older showed no significantly elevated risk for stroke immediately after receiving either COVID-19 bivalent vaccine [ 16 ]. However, among beneficiaries who had a stroke after getting either COVID-19 bivalent vaccine along with a high-dose or adjuvanted influenza vaccine, there was a significant association between vaccination and nonhemorrhagic stroke within 22 to 42 days for the Pfizer-BioNTech COVID-19 bivalent vaccine.…”