COVID-19, Vaccination, and the Heart: Understanding Injury Pathways and Clinical Implications

Cardiovascular involvement in SARS-CoV-2 infection and following vaccination has emerged as a clinically relevant phenomenon with distinct yet overlapping mechanisms. Myocardial injury in COVID-19 results from a complex interplay between direct viral ef-fects, immune-mediated inflammation, endothelial dysfunction, oxidative stress, and, in rare occasions, cytokine storm. The virus primarily binds to ACE2 receptors, which are highly expressed in endothelial cells and pericytes, leading to microvascular damage and a systemic prothrombotic state. Additional viral entry pathways, including CD147, Neu-ropilin-1, and CD26, further contribute to vascular and myocardial injury, which is a ra-ther immune-driven process rather than a direct cytopathic one. Histopathological studies that reveal macrophage-rich infiltrates, microthrombosis, and patchy fibrosis support the immune-driven process theory. In contrast, vaccine-associated myocarditis – predomi-nantly reported following mRNA vaccines – presents a self-limiting clinical course, with mechanisms probably involving molecular mimicry, aberrant immune activation, or hy-persensitivity reactions. Despite an increased incidence in young males after the second dose, the overall risk remains low compared to infection-related myocarditis. Under-standing the pathophysiological interplay between infection- and vaccine-related cardiac involvement is essential for accurate risk assessment, improved diagnostic strategies, and targeted therapeutic approaches. Future research should focus on elucidating immune pathways, refining biomarkers, and developing personalized management strategies in order to mitigate cardiovascular sequelae of both COVID-19 and vaccination.