BACKGROUNDThe COVID-19 pandemic adversely affected the severity and prognosis of patients with acute myocardial infarction (MI) caused by atherothrombosis (type 1 MI). The effect, if any, of COVID-19 vaccination and natural SARS-CoV2 serologic immunity in these patients is unclear. Our aim was to analyze the association between the severity and outcome of patients with type 1 MI and their previous SARS-CoV2 vaccination and serostatus.METHODSA single-center retrospective cohort study conducted between March 1, 2020 and March 1, 2023. Clinical and follow-up information was collected from medical records and patients. Total antibodies (IgM, IgA, IgG) to nucleocapsid (N) antigens were measured by ECLIA (electrochemiluminescence-based immunoassay) to test the immune response to natural infection. If positive, IgM and IgG antibodies to spike (S) surface antigens were measured by CLIA to test the immune response to vaccine or natural infection. Multivariable logistic regression analysis was performed, adjusting for age, sex, hypertension, diabetes, and dyslipidemia.RESULTSTotal sample of 949 patients, 656 with ST-segment elevation MI (STEMI) and 293 with non-ST-segment elevation MI (NSTEMI). Mean age was 64 (SD 13) years, 80 % men. Pre-admission vaccination status was: ≥ 1 dose, 53 % of patients; complete vaccination, 49 %; first booster dose, 25 %. The majority (84 %) of vaccines administered were mRNA-based. Six months after MI, 92 (9.7 %) patients had a major adverse cardiac event (MACE) and 50 died; 11 % of patients had severe heart failure or cardiogenic shock (Killip III-IV) after STEMI. Vaccinated patients with STEMI and positive serology (Pos/Vax group) had a higher risk of Killip III-IV on admission: OR 2.63 (1.27-5.44), p = 0.010. SARS-CoV-2 S-specific IgG titers were highest in this group (median > 2080 AU/mL, [IQR 1560- >2080] vs 91 [32-198] in the unvaccinated group). In the overall sample, a higher incidence of 6-month MACE was not demonstrated (OR 1.89 [0.98-3.61], p = 0.055).CONCLUSIONSThe combination of vaccination and natural SARS-CoV2 infection was associated with the development of severe heart failure and cardiogenic shock in patients with STEMI, possibly related to an increased serological response.