Integrated Management of Long COVID: Fatigue, Emerging Evidence, and Therapeutic Innovations

Dear Colleagues,

Long COVID has emerged as a significant global health challenge, affecting a substantial proportion of individuals following acute SARS-CoV-2 infection. Patients frequently experience persistent and heterogeneous symptoms, including fatigue, dyspnea, cognitive impairment, autonomic disturbances, and psychological distress. Among these manifestations, fatigue is consistently reported as one of the most prevalent and disabling symptoms, affecting approximately 40–60% of patients in observational cohorts. Despite its high prevalence and profound impact on daily functioning and quality of life, fatigue remains difficult to quantify and manage, often overlapping with medically unexplained symptoms and conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Unified and evidence-based management strategies for long COVID remain insufficient. Clinicians and patients alike face considerable uncertainty regarding optimal therapeutic approaches, which may include pharmacological interventions, structured rehabilitation programs, pacing strategies, integrative medicine, and other supportive or complementary modalities. While rehabilitation is widely regarded as an essential component of care, excessive or poorly individualized exercise may exacerbate symptoms in certain patients, underscoring the importance of balanced and patient-centered management. Meanwhile, advances in immunology, endocrinology, autonomic function assessment, biomarker discovery, and digital health technologies are expanding opportunities to better understand and treat persistent post-COVID conditions.

As a general physician in Japan who was involved in establishing a COVID-19 aftercare clinic in the university hospital and has been engaged in the clinical management and research of long COVID, I recognize the urgent need to consolidate emerging knowledge and practical experience in this field.

This Special Issue aims to present and disseminate the most recent advances in the clinical management of long COVID, with particular attention to fatigue and other persistent multisystem symptoms. We consider contributions addressing therapeutic strategies, emerging evidence, and ongoing clinical challenges in both research and practice.

Topics of interest for publication include, but are not limited to, the following:

• Clinical management strategies for long COVID;
• Assessment and treatment of fatigue;
• Pharmacological interventions;
• Rehabilitation models and pacing strategies;
• Integrative medicine and traditional therapies;
• Biomarker research and pathophysiological mechanisms;
• Autonomic dysfunction and endocrine involvement;
• Digital health and AI-supported interventions;
• Multidisciplinary and patient-centered care approaches.

Dr. Yuki Otsuka
Guest Editor

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