Immunothrombotic Features of Coronary Thrombi in Myocardial Infarction after SARS-CoV-2 Vaccination

<jats:p>Background: Neutrophil extracellular traps (NETs) contribute to immunothrombosis and arterial thrombosis. Mechanisms underlying myocardial infarction after SARS-CoV-2 vaccination remain poorly understood. Objectives: To investigate histopathologic and immunothrombotic features of coronary thrombi in patients with ST-elevation myocardial infarction (STEMI) after SARS-CoV-2 vaccination. Methods: We performed a retrospective matched cohort study including patients with STEMI undergoing primary percutaneous coronary intervention between January 2021 and March 2023. Coronary thrombi obtained by aspiration were analyzed by histopathology, immunohistochemistry, and confocal microscopy for NET detection. Vaccinated and unvaccinated patients were matched by age and sex. Associations between vaccination status and thrombus characteristics were assessed after adjustment for SARS-CoV-2 serologic status. Results: Among 44 matched patients (23 vaccinated and 21 unvaccinated), NETs were identified in 14 vaccinated patients (61%) and 5 unvaccinated patients (24%; P = .01). Vaccination was associated with increased odds of NET-positive thrombi after adjustment for SARS-CoV-2 serology (odds ratio, 5.1; 95% CI, 1.36— 19.45; P = .02). No associations were observed between vaccination and polymorphonuclear cell density, fibrin deposits, plaque fragments, or anti–platelet factor 4 staining. Among patients vaccinated within 100 days before STEMI, NET-positive thrombi were associated with shorter intervals between vaccination and myocardial infarction (median [IQR], 25 [11—64] vs 57 [40—84] days; P = .02). Conclusions: SARS-CoV-2 vaccination was associated with increased NET presence in coronary thrombi from patients with STEMI, suggesting a potential NET-mediated immunothrombotic mechanism independent of classical vaccine-induced immune thrombotic thrombocytopenia.</jats:p>