scholarly journals Hypothesis: Neuroglia Activation due to Increased Peripheral and CNS Proinflammatory Cytokines/Chemokines with Neuroinflammation May Result in Long COVID

Neuroglia ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 7-35
Author(s):  
Melvin R. Hayden
Keyword(s):  
Metabolic Stress ◽  
Chronic Fatigue ◽  
The United States ◽  
Common Denominator ◽  
Stress Injury ◽  
Fatigue Syndrome ◽  
Obesity And Diabetes ◽  
Transmission Electron ◽  
Spanish Flu ◽  
Historical Accounts

The COVID-19 pandemic has paralleled the great Spanish flu pandemic of 1918–1919 in the United States. Previous historical accounts have strongly suggested a post-viral syndrome and, currently, a post-COVID-19 viral syndrome is unquestionable, which shares many of the characteristics of myalgic encephalomyelitis/chronic fatigue syndrome that is present globally. The original term for this post-acute sequela of SARS-CoV-2 (PASC) was termed long haulers by those who were affected with this syndrome and it is now termed long COVID (LC) or PASC. International researchers and clinicians are desperately trying to better understand the pathobiological mechanisms possibly involved in this syndrome. This review aims to summarize many of the cumulated findings associated with LC/PASC and provides supportive and representative illustrations and transmission electron micrographic remodeling changes within brain tissues associated with a stress type of injury as occurs in the classic db/db and novel BTBR ob/ob obesity and diabetes mellitus mice models. These models are utilized to merely provide a response to metabolic stress injury wound healing mechanisms that are also present in humans. This review posits that neuroglial activation and chronic neuroinflammation may be a common denominator for the development of the complex LC/PASC syndrome following acute COVID-19 due to SARS-CoV-2.

scholarly journals Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Comprehensive Review

Diagnostics ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 91 ◽  
Author(s):  
Mateo Cortes Rivera ◽  
Claudio Mastronardi ◽  
Claudia Silva-Aldana ◽  
Mauricio Arcos-Burgos ◽  
Brett Lidbury
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Age Of Onset ◽  
Chronic Fatigue ◽  
The United States ◽  
Myalgic Encephalomyelitis ◽  
World Health ◽  
Fatigue Syndrome ◽  
Control And Prevention ◽  
The Moment ◽  
Health Organization

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology that is recognized by the World Health Organization (WHO) and the United States Center for Disease Control and Prevention (US CDC) as a disorder of the brain. The disease predominantly affects adults, with a peak age of onset of between 20 and 45 years with a female to male ratio of 3:1. Although the clinical features of the disease have been well established within diagnostic criteria, the diagnosis of ME/CFS is still of exclusion, meaning that other medical conditions must be ruled out. The pathophysiological mechanisms are unclear but the neuro-immuno-endocrinological pattern of CFS patients gleaned from various studies indicates that these three pillars may be the key point to understand the complexity of the disease. At the moment, there are no specific pharmacological therapies to treat the disease, but several studies’ aims and therapeutic approaches have been described in order to benefit patients’ prognosis, symptomatology relief, and the recovery of pre-existing function. This review presents a pathophysiological approach to understanding the essential concepts of ME/CFS, with an emphasis on the population, clinical, and genetic concepts associated with ME/CFS.

scholarly journals A Rose By Any Other Name?

2016 ◽  
Vol 10 (4) ◽  
Author(s):  
Richard Marlin PhD
Keyword(s):  
United States ◽  
Chronic Fatigue Syndrome ◽  
Diagnostic Criteria ◽  
Functional Impairment ◽  
Chronic Fatigue ◽  
The United States ◽  
Myalgic Encephalomyelitis ◽  
Expert Committee ◽  
Institute Of Medicine ◽  
Fatigue Syndrome

In February of this year, an expert committee of the United States Institute of Medicine (IOM) released a lengthy report in which its members reviewed diagnostic criteria and proposed a new label for chronic fatigue syndrome, also historically referred to as myalgic encephalomyelitis.1 The committee’s proposed new label for this illness is Systemic Exertion Intolerance Disease. The report refers to the fact that a sizeable population is diagnosed with this illness, which causes considerable suffering and functional impairment. Many patients also feel stigmatized because of the label chronic fatigue syndrome.

scholarly journals Homebound versus Bedridden Status among Those with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Healthcare ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 106
Author(s):  
Karl Conroy ◽  
Shaun Bhatia ◽  
Mohammed Islam ◽  
Leonard A. Jason
Keyword(s):  
United States ◽  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
The United States ◽  
Myalgic Encephalomyelitis ◽  
Fatigue Syndrome ◽  
Study Participants

Persons living with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) vary widely in terms of the severity of their illness. It is estimated that of those living with ME/CFS in the United States, about 385,000 are homebound. There is a need to know more about different degrees of being homebound within this severely affected group. The current study examined an international sample of 2138 study participants with ME/CFS, of whom 549 were severely affected (operationalized as ‘Homebound’). A subsample of 89 very severely affected participants (operationalized as ‘Homebound-bedridden’) was also examined. The findings showed a significant association between severely and very severely affected participants within the post-exertional malaise (PEM) symptom domain. The implications of these findings are discussed.

scholarly journals Deficient Butyrate-Producing Capacity in the Gut Microbiome of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients is Associated with Fatigue Symptoms

2021 ◽  
Author(s):  
Cheng Guo ◽  
Xiaoyu Che ◽  
Thomas Briese ◽  
Orchid Allicock ◽  
Rachel A. Yates ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Gut Microbiome ◽  
Symptom Severity ◽  
Chronic Fatigue ◽  
The United States ◽  
Small Sample ◽  
Myalgic Encephalomyelitis ◽  
Healthy Controls ◽  
Shotgun Metagenomics ◽  
Fatigue Syndrome

Abstract Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, debilitating disease of unknown cause for which there is no specific therapy. Patients suffering from ME/CFS commonly experience persistent fatigue, post-exertional malaise, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever and irritable bowel syndrome (IBS). Recent evidence implicates gut microbiome dysbiosis in ME/CFS. However, most prior studies are limited by small sample size, differences in clinical criteria used to define cases, limited geographic sampling, reliance on bacterial culture or 16S rRNA gene sequencing, or insufficient consideration of confounding factors that may influence microbiome composition. In the present study, we evaluated the fecal microbiome in the largest prospective, case-control study to date (n=106 cases, n=91 healthy controls), involving subjects from geographically diverse communities across the United States. Results: Using shotgun metagenomics and qPCR and rigorous statistical analyses that controlled for important covariates, we identified decreased relative abundance and quantity of Faecalibacterium , Roseburia , and Eubacterium species and increased bacterial load in feces of subjects with ME/CFS. These bacterial taxa play an important role in the production of butyrate, a multifunctional bacterial metabolite that promotes human health by regulating energy metabolism, inflammation, and intestinal barrier function. Functional metagenomic and qPCR analyses were consistent with a deficient microbial capacity to produce butyrate along the acetyl-CoA pathway in ME/CFS. Metabolomic analyses of short-chain fatty acids (SCFAs) confirmed that fecal butyrate concentration was significantly reduced in ME/CFS. Further, we found that the degree of deficiency in butyrate-producing bacteria correlated with fatigue symptom severity among ME/CFS subjects. Finally, we provide evidence that IBS comorbidity is an important covariate to consider in studies investigating the microbiome of ME/CFS subjects, as differences in microbiota alpha diversity, some bacterial taxa, and propionate were uniquely associated with self-reported IBS diagnosis. Conclusions: Our findings indicate that there is a core deficit in the butyrate-producing capacity of the gut microbiome in ME/CFS subjects compared to healthy controls. The relationships we observed among symptom severity and these gut microbiome disturbances may be suggestive of a pathomechanistic linkage, however, additional research is warranted to establish any causal relationship. These findings provide support for clinical trials that explore the utility of dietary, probiotic and prebiotic interventions to boost colonic butyrate production in ME/CFS.

scholarly journals Metabolic features of chronic fatigue syndrome

2016 ◽  
Vol 113 (37) ◽  
pp. E5472-E5480 ◽  
Author(s):  
Robert K. Naviaux ◽  
Jane C. Naviaux ◽  
Kefeng Li ◽  
A. Taylor Bright ◽  
William A. Alaynick ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Metabolic Response ◽  
Characteristic Curve ◽  
Chronic Fatigue ◽  
The United States ◽  
Receiver Operator Characteristic Curve ◽  
Institute Of Medicine ◽  
Fatigue Syndrome ◽  
Evolutionarily Conserved ◽  
Branch Chain Amino

More than 2 million people in the United States have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We performed targeted, broad-spectrum metabolomics to gain insights into the biology of CFS. We studied a total of 84 subjects using these methods. Forty-five subjects (n = 22 men and 23 women) met diagnostic criteria for ME/CFS by Institute of Medicine, Canadian, and Fukuda criteria. Thirty-nine subjects (n = 18 men and 21 women) were age- and sex-matched normal controls. Males with CFS were 53 (±2.8) y old (mean ± SEM; range, 21–67 y). Females were 52 (±2.5) y old (range, 20–67 y). The Karnofsky performance scores were 62 (±3.2) for males and 54 (±3.3) for females. We targeted 612 metabolites in plasma from 63 biochemical pathways by hydrophilic interaction liquid chromatography, electrospray ionization, and tandem mass spectrometry in a single-injection method. Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism. Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of 94% [95% confidence interval (CI), 84–100%] in males using eight metabolites and 96% (95% CI, 86–100%) in females using 13 metabolites. Our data show that despite the heterogeneity of factors leading to CFS, the cellular metabolic response in patients was homogeneous, statistically robust, and chemically similar to the evolutionarily conserved persistence response to environmental stress known as dauer.

scholarly journals Distinct plasma immune signatures in ME/CFS are present early in the course of illness

2015 ◽  
Vol 1 (1) ◽  
pp. e1400121 ◽  
Author(s):  
Mady Hornig ◽  
José G. Montoya ◽  
Nancy G. Klimas ◽  
Susan Levine ◽  
Donna Felsenstein ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Chronic Fatigue ◽  
The United States ◽  
Sample Collection ◽  
Course Of Illness ◽  
Illness Duration ◽  
Fatigue Syndrome ◽  
Immune Signatures ◽  
Duration Of Illness ◽  
Relationship Of

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS (n= 52) relative to healthy controls (n= 348) that are not present in subjects with longer duration of illness (n= 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS.

Long- and short-term blood pressure andRR-interval variability and psychosomatic distress in chronic fatigue syndrome: authors’ reply 1

1999 ◽  
Vol 97 (3) ◽  
pp. 319 ◽  
Author(s):  
D.A. DUPREZ ◽  
M.L. DE BUYZERE ◽  
B. DRIEGHE ◽  
F. VANHAVERBEKE ◽  
Y. TAES ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Short Term ◽  
Fatigue Syndrome
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