Exploring the Multisystem Features of Long COVID

Dear Colleagues,

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is a complex, multisystem condition where symptoms persist for weeks or months after acute COVID-19. Characterized by persistent symptoms that span multiple organ systems—ranging from neurological and cardiovascular to respiratory and gastrointestinal systems—Long COVID poses significant challenges in diagnosis, management, and rehabilitation. Despite increasing awareness, its pathophysiology remains only partially understood, and evidence-based treatments are still lacking. Emerging research also suggests that genetics may influence susceptibility, severity, and symptom persistence. Key areas of focus include the following: 1) genetic susceptibility to Long COVID (e.g., HLA, FOXP4, ACE2, and TMPRSS2); 2) immune and inflammatory genes (e.g., TLR3, TLR7, IRF7, IFN, and autoantibody IFN); 3) overlap with other post-viral syndromes, e.g., Long COVID shares features with ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) and dysautonomia (e.g., POTS); 4) epigenetics and viral persistence, e.g., SARS-CoV-2 may alter host gene expression (e.g., via DNA methylation), thereby exacerbating long-term symptoms. Genetic differences in viral clearance (e.g., APOBEC3 antiviral genes) could allow persistent viral fragments to trigger immune reactions; and 5) genetics likely interacts with age, sex (women are more affected), and prior health conditions.

This Special Issue aims to explore the multisystemic nature of Long COVID through original research, reviews, and clinical insights, fostering a multidisciplinary approach that integrates perspectives from infectious diseases, internal medicine, neurology, cardiology, and beyond. By shedding light on the long-term consequences of SARS-CoV-2 infection, we hope to contribute to improved patient care and the development of targeted therapeutic strategies. We look forward to your submissions.

Dr. Andrea Marino
Dr. Emmanuele Venanzi Rullo
Guest Editors

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• long COVID
• post-acute COVID-19
• multisystem involvement
• PASC
• COVID-19 sequelae
• chronic symptoms
• SARS-CoV-2
• rehabilitation
• pathophysiology
• clinical management
• genomics studies
• polygenic risk scores (PRS)
• personalized medicine
• biomarker development