Cardiovascular sequelae of Long COVID: immune dysregulation inflammation as central drivers

Long coronavirus disease 2019 (Long COVID-19), also referred to as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has emerged as a major global health challenge. Common manifestations include fatigue, dyspnea, cognitive dysfunction, and exercise intolerance. Beyond these systemic manifestations, the enduring cardiovascular manifestations are increasingly identified as core characteristics of Long COVID-19 syndromes secondary to SARS-CoV-2 infection, encompassing myocarditis, ischemic and non-ischemic heart disease, arrhythmias, heart failure, and thrombotic events. Accumulating evidence suggests that immune dysregulation and persistent inflammation are central drivers of cardiovascular injury in Long COVID. Persistent activation of innate and adaptive immune pathways fosters endothelial injury, thrombo-inflammation, and adverse myocardial remodeling. In this review, we focus on current clinical and experimental evidence to delineate the immune-mediated mechanisms underlying cardiovascular sequelae in Long COVID and explore potential therapeutic strategies targeting persistent inflammation and immune dysregulation.