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Advances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 4290

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Guest Editor
Department of Microbiology and Immunology, Reno School of Medicine, University of Nevada, Reno, NV 89557, USA
Interests: gut-brain axis; neuroimmune disease; GI-associated plasmacytoid dendritic cells; Alzheimer’s disease; myalgic encephalomyelitis
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Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue, “Advances of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)”.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness of unknown etiology, characterized by multiple physical symptoms and comorbid conditions. Symptoms often reported by those with ME/CFS include unexplained fatigue that lasts for more than six months, post-exertional malaise, neurocognitive problems, unrefreshing sleep, and gastrointestinal issues. Clinical laboratory findings often include inflammatory sequelae, metabolic disturbances, self-reactive antibodies, and immune cell abnormalities. Although many who suffer from ME/CFS report that they developed the condition following a “flu-like” illness from which they never fully recovered, an etiological agent has not been reproducibly identified. Likewise, many individuals infected by the SARS-CoV-2 virus often never fully recover and present with symptoms that significantly overlap with those of ME/CFS. This syndrome is typically referred to as long COVID-19 or post-acute sequelae of SARS COV-2 infection. In this Special Issue, which addresses the advances in research regarding myalgic encephalomyelitis/chronic fatigue syndrome, we aim to publish original research papers and reviews that focus on the involvement of the immune system in ME/CFS. Reports that leverage commonalities between ME/CFS and long COVID-19 to identify the mechanisms behind immune abnormalities are highly encouraged.

Dr. Vincent C. Lombardi
Guest Editor

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Keywords

  • ME/CFS
  • PASC
  • long COVID-19
  • inflammation
  • innate immunity
  • adaptive immunity
  • mast cell activation
  • post-infection syndrome
  • metabolism
  • autoantibodies

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Published Papers (1 paper)

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Research

12 pages, 3191 KiB  
Article
Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID
by Gong-Hua Li, Fei-Fei Han, Efthymios Kalafatis, Qing-Peng Kong and Wenzhong Xiao
Int. J. Mol. Sci. 2025, 26(13), 6082; https://doi.org/10.3390/ijms26136082 - 25 Jun 2025
Viewed by 3250
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID are complex multisystem conditions that pose significant challenges in healthcare. Accumulated research evidence suggests that ME/CFS and Long COVID exhibit overlapping metabolic symptoms, indicating potential shared metabolic dysfunctions. This study aims to systematically explore shared [...] Read more.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID are complex multisystem conditions that pose significant challenges in healthcare. Accumulated research evidence suggests that ME/CFS and Long COVID exhibit overlapping metabolic symptoms, indicating potential shared metabolic dysfunctions. This study aims to systematically explore shared metabolic disturbances in the muscle tissue of patients. Utilizing genome-wide metabolic modeling, we identified key metabolic irregularities in the muscle of patients with ME/CFS, notably the downregulation of the alanine and aspartate metabolism pathway and the arginine and proline metabolism pathway. Further, in silico knockout analyses suggested that supplementation with aspartate (ASP) or asparagine (ASN) could potentially ameliorate these metabolic deficiencies. In addition, assessments of metabolomic levels in Long COVID patients also showed the significant downregulation of ASP during post-exertional malaise (PEM) in both muscle and blood. Consequently, we propose that a combination of l-ornithine and l-aspartate (LOLA) is a potential candidate to alleviate metabolic symptoms in ME/CFS and Long COVID for future clinical trials. Full article
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