Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition arising in susceptible people, predominantly following viral infection, but also other stressful events. The susceptibility factors discussed here are both genetic and environmental although not well understood. While the dysfunctional physiology in ME/CFS is becoming clearer, understanding has been hampered by different combinations of symptoms in each affected person. A common core set of mainly neurological symptoms forms the modern clinical case definition, in the absence of an accessible molecular diagnostic test. This landscape has prompted interest in whether ME/CFS patients can be classified into a particular phenotype/subtype that might assist better management of their illness and suggest preferred therapeutic options. Currently, the same promising drugs, nutraceuticals, or behavioral therapies available can be beneficial, have no effect, or be detrimental to each individual patient. We have shown that individuals with the same disease profile exhibit unique molecular changes and physiological responses to stress, exercise and even vaccination. Key features of ME/CFS discussed here are the possible mechanisms determining the shift of an immune/inflammatory response from transient to chronic in ME/CFS, and how the brain and CNS manifests the neurological symptoms, likely with activation of its specific immune system and resulting neuroinflammation. The many cases of the post viral ME/CFS-like condition, Long COVID, following SARS-CoV-2 infection, and the intense research interest and investment in understanding this condition, provide exciting opportunities for the development of new therapeutics that will benefit ME/CFS patients.

A Narrative Review on Gut Microbiome Disturbances and Microbial Preparations in ME/CFS: Implications for Long COVID

“…Finally, focusing on the manipulation of the microbiome followed by other areas highlighted to be of the most therapeutic value including energy metabolism, chronic inflammation, fluctuating neuroinflammation and management of the response to stress [13] could provide holistic background supporting the most promising probiotic interaction in the care offered for patients suffering from post-viral syndromes.…”

“…Reported association between low levels of butyrate, as well as reduced abundance of SCFAs producing bacteria in expense of gut pathogens with persisting GI and neurological symptoms in these individuals, highlighted the need for novel strategies for microbiome-tailored disease prevention and treatment. The increased interest and research activity initiated during COVID-19 pandemic, based on the certain similarity observed in pathophysiology of both post-viral syndromes, in particularly in the gut microbiome, may accelerate the progress in developing evidence-based therapeutic options for ME/CFS [13] such as use of microbial preparations.…”

“…Interestingly, Long COVID patients also have reported other dysfunctions, which previously were associated with, including neurologic pain, neurocognitive and psychiatric symptoms, however with no cases of rash, as well as olfactory and gustatory dysfunction [11] (Figure 1). Although the exact aetiology of ME/CFS, neither Long COVID still needs to be determined, evidence to date indicate as post-viral syndromes, being most likely triggered by the infectious agent, such as Epstein Barr Virus [12] and SARS-CoV-2 in Long COVID [13], respectively, also share biological abnormalities, with examples of the cognitive deficits, including impaired attention and information processing speed, dysregulation of the hypothalamic-pituitary (HP) axis, and abnormal immune cytokine profile [14], characterized by high auto-antibodies titres against neural and autonomic targets [15,16] including neurotransmitter receptors against nuclear and membrane structures, such as cardiopin and phospholipids, neurotransmitter receptors (e.g., muscarinic M1 acetylcholine receptor (AChR) and ß1-and ß2-adrenergic receptors (AdR) and M2/3 [17]); as well as and increased levels of proinflammatory mediators, interleukin (IL) IL-1 (IL-1α, IL-1β), IL-4, IL-5, IL-6, and IL-12, TNF-α, IL-10, IL-13, IL-16, INF-γ, and IL-17, IL-17A (but reduced IL-17F) [18][19][20], further linked with severity of after mentioned symptoms [21]. In particularly, metabolic abnormalities along with mitochondrial dysfunction and impaired redox balance [22] characterized by increased oxidative toxicity and lowered antioxidant defenses were associated with the development of symptoms of pain and hyper-sensitivity [23] and severity of neuropsychiatric symptoms in both ME/CFS [18] and Long COVID [24].…”

Telemonitoring bei pädiatrischem Post-COVID-Syndrom

“…Es kommen medikamentöse und nicht-medikamentöse Maßnahmen zum Einsatz, z. B. Analgetika, Inhalativa, Kreislaufmedikamente, Antihistaminika, Psycho- sowie Physiotherapie 5 , 7 , 18 . Im Falle von Belastungsintoleranz mit PEM hat sich — basierend auf dem Wissen zu ME/CFS — das Pacing als hilfreiche Strategie bewährt.…”

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview

“…Long COVID can affect individuals varying in the severity of initial infection, including asymptomatic children/adolescents [19]. Long-term longitudinal clinical and -omics studies are needed to determine if long COVID can lead to distinct subgroups using cluster analysis in some individuals with ME/CFS and FM [20,21]. ME/CFS, FM, and long COVID can occur independently or an coexist in some individuals with other comorbid health conditions, such as irritable bowel syndrome (IBS), and mood disorders, such as anxiety/depression, which can further complicate the understanding and management of these conditions [22].…”