LONG COVID AND POST-ACUTE SEQUELAE: PATHOPHYSIOLOGY, BIOMARKERS, AND POTENTIAL REPURPOSED DRUG THERAPIES

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection, affects a substantial proportion of individuals following acute COVID-19, with symptoms persisting for weeks to months. Common manifestations include fatigue, cognitive impairment, dyspnea, chest pain, and autonomic dysfunction. The pathophysiology is multifactorial, involving persistent viral reservoirs, immune dysregulation, endothelial dysfunction, microclot formation, and tissue damage. Identifying reliable biomarkers has been challenging, but studies have reported alterations in inflammatory cytokines, autoantibodies, markers of coagulation, and metabolomic profiles. No approved therapies exist for long COVID, but several repurposed drugs are being investigated, including antivirals (nirmatrelvir/ritonavir, molnupiravir), anti-inflammatory agents (colchicine, corticosteroids), anticoagulants/antiplatelets, metformin, and drugs targeting autonomic or neurological symptoms. This review critically examines the current understanding of long COVID pathophysiology, the state of biomarker discovery, and the evidence for repurposed drug therapies, focusing on literature through early 2025. The heterogeneity of long COVID phenotypes complicates clinical trial design, and many early trials have been small or inconclusive. Future directions include better phenotyping, adaptive platform trials, and mechanistic biomarker-guided therapy. Until effective treatments are established, multidisciplinary supportive care remains central.