Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract

Long-COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome are disabling diseases characterised by ongoing fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome typically follows viral infections, whereas Long-COVID exclusively follows SARS-CoV-2 infection, with overlapping but distinct features. This review uses comprehensive searches of online databases to compare their clinical presentations, pathophysiologies, and treatments. Both Long-COVID and ME/CFS appear to involve multifactorial mechanisms, including viral persistence, immune dysregulation, endothelial dysfunction, and autoimmunity, though their relative contributions remain uncertain. Symptom management strategies are consistent, however. Cognitive behaviour therapy has been successful, and there are minimal drug treatments. Graded exercise therapy occupies a contested place, recommending individualised pacing and multidisciplinary rehabilitation. Common and exclusive mechanisms must be identified to formulate valuable therapies. A more significant body of research focusing on immune dysfunction as a pathogenic mechanism for advancing the disease and enabling more effective therapies and diagnostics is needed.

Keywords: ME/CFS; Myalgic encephalomyelitis; chronic fatigue syndrome; long-COVID.

Figure 2

Proposed Pathogenic Mechanisms Underlying Long-COVID and ME/CFS. Following viral infection, persistent immune activation leads to cytokine imbalance, autoimmunity, and chronic inflammation. Key proposed mechanisms driving chronic symptoms in both Long-COVID and ME/CFS include mitochondrial dysfunction, vascular impairment, neuroinflammation, immune dysregulation, and gut dysbiosis, all contributing to disease pathology. These interconnected pathways sustain multisystem dysfunction characteristics of Long-COVID and ME/CFS. Created using images from [74]. [Made by Maysam Salim Homadi and Gergana Angelova].

Figure 1

Names of the nine genes that are shared between Long-COVID and ME/CFS. [Made by Maysam Salim Homadi].