The Pathophysiology of Long COVID: Mechanisms and Management Strategies

Long COVID, also known as post-acute sequelae of SARS-CoV-۲ infection (PASC), has emerged as a significant public health challenge, affecting millions of individuals globally. It is characterized by persistent or new symptoms lasting weeks to months beyond the acute phase of COVID-۱۹, including fatigue, dyspnea, cognitive impairment, autonomic dysfunction, and musculoskeletal pain. The underlying pathophysiology is multifactorial and remains under investigation. Current evidence suggests that persistent viral reservoirs in tissues, chronic immune activation, autoimmunity, endothelial dysfunction, microvascular injury, and mitochondrial impairment play major roles. Neurological and autonomic disturbances, along with psychosocial and epigenetic influences, further contribute to the complexity of the syndrome. Management strategies are primarily supportive and multidisciplinary, focusing on symptom relief, rehabilitation, and psychosocial care. Approaches include pulmonary and cardiovascular rehabilitation, pacing and energy conservation for fatigue, pharmacological interventions for dysautonomia, and cognitive therapy for neurocognitive symptoms. Emerging treatments such as immunomodulators, antiviral agents, anticoagulants, and mitochondrial support therapies are under investigation. Despite progress, challenges remain in defining diagnostic criteria, identifying biomarkers, and tailoring personalized interventions. Long COVID represents not only a biomedical issue but also a socioeconomic burden, requiring coordinated healthcare strategies and global research efforts. Understanding its mechanisms and developing effective management approaches are essential to mitigate its long-term impact on individuals and healthcare systems.

Keywords:

COVID , anticoagulants , Healthcare Systems , SARS-CoV-۲ Infection (PASC) , Pharmacological Interventions