Long COVID: mechanisms of disease, multisystem sequelae, and prospects for treatment.

Abstract

Long COVID has emerged as a significant global health issue, affecting individuals across a wide spectrum of initial disease severity. While its definition and prevalence vary across studies, persistent symptoms such as fatigue, cognitive dysfunction, respiratory difficulties, and cardiovascular complications have been widely reported. Multiple pathophysiological mechanisms have been proposed, including incomplete viral clearance, reactivation of latent viruses, immune dysregulation, autoimmunity, endothelial dysfunction, microbiome alterations, and mitochondrial impairment. These interconnected processes are thought to contribute to chronic inflammation and multi-organ disease. To date, there are no established therapies for Long COVID, and management primarily focuses on symptomatic relief and rehabilitation. Vaccination has been shown to reduce the incidence of Long COVID, and emerging strategies, including antiviral agents, immune-modulating therapies, microbiome restoration, and mitochondria-targeted interventions, are under investigation. This review summarizes the current understanding of the epidemiology, pathophysiology, organ-specific manifestations, and potential therapeutic approaches for Long COVID, aiming to provide insights into future research directions and clinical management strategies.