Long COVID and Cardiovascular Sequelae: Mechanistic Insights and Clinical Management

Background: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant public health concern, with a growing subset of individuals experiencing persistent cardiovascular symptoms months after acute infection. These include chest pain, palpitations, dyspnea, postural tachycardia, and exercise intolerance, even in previously healthy individuals. Mounting evidence suggests that Long COVID–associated cardiovascular complications are driven by multifactorial pathophysiology involving endothelial dysfunction, autonomic imbalance, persistent inflammation, microvascular thrombosis, and myocardial injury. Understanding these mechanisms is essential for risk stratification and the development of targeted management strategies. Methods and Results: This review integrates findings from clinical cohorts, imaging studies, and translational models to characterize the cardiovascular manifestations of Long COVID. Cardiac MRI and echocardiography frequently reveal subclinical myocardial fibrosis, pericardial effusion, or diastolic dysfunction. Biomarkers such as troponin, NT-proBNP, D-dimer, and IL-6 remain elevated in a subset of patients, correlating with symptom severity and functional limitation. Mechanistically, SARS-CoV-2–induced endothelial damage and immune dysregulation perpetuate vascular inflammation and autonomic instability. Evidence also points to viral persistence, autoimmunity, and mitochondrial dysfunction as contributors to post-viral cardiac syndromes. Clinically, multidisciplinary management is recommended, combining cardiology, rehabilitation, and autonomic neurology services. Therapeutic strategies under investigation include beta-blockers, anti-inflammatory agents, low-dose anticoagulation, and structured exercise programs. Conclusion: Long COVID poses a sustained cardiovascular burden through diverse and overlapping pathophysiologic mechanisms. Comprehensive evaluation and individualized management approaches are essential to address its complex clinical spectrum.