Abstract
Vaccination against coronavirus disease 2019 (COVID-19) is the safest and most effective strategy for controlling the pandemic. However, some cases of acute cardiac events following vaccine administration have been reported, including myocarditis and myocardial infarction (MI). While post-vaccine myocarditis has been widely discussed, information about post-vaccine MI is scarce and heterogenous, often lacking in histopathological and pathophysiological details. We hereby present five cases (four men, mean age 64 years, range 50-76) of sudden death secondary to MI and tightly temporally related to COVID-19 vaccination. In each case, comprehensive macro- and microscopic pathological analyses were performed, including post-mortem cardiac magnetic resonance, to ascertain the cause of death. To investigate the pathophysiological determinants of MI, toxicological and tryptase analyses were performed, yielding negative results, while the absence of anti-platelet factor 4 antibodies ruled out vaccine-induced thrombotic thrombocytopenia. Finally, genetic testing disclosed that all subjects were carriers of at least one pro-thrombotic mutation. Although the presented cases do not allow us to establish any causative relation, they should foster further research to investigate the possible link between COVID-19 vaccination, pro-thrombotic genotypes, and acute cardiovascular events.