Tag: 2023

The importance of estimating prevalence of ME/CFS in future epidemiological studies of long COVID

Abstract:

The resolution of the COVID-19 pandemic is giving rise to another public health challenge due to the explosion of long COVID (LC) cases. In many cases, LC results in persistent fatigue, post-exertional malaise (PEM), and other debilitating symptoms that resemble the clinical manifestation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The similarity of these two diseases suggests that future epidemiological studies of LC could take the opportunity to also estimate the prevalence of ME/CFS at a minimal cost.

With this opportunity in mind, we revisited the most consensual case definitions of ME/CFS for research purposes. We then compared the symptoms assessed at the participants’ enrollment in the UK ME/CFS Biobank with those documented in three systematic reviews encompassing hundreds of LC epidemiological studies. We found that published epidemiological studies of LC did not consistently assess or report the prevalence of PEM, which is a compulsory symptom for ME/CFS diagnosis. However, these studies assessed many neuro-cognitive, immunologic, and autonomic symptoms.

In this scenario, we recommend that the estimation of ME/CFS prevalence in the context of LC epidemiology is easily achievable by deploying tested and validated diagnosis tools used in ME/CFS. The knowledge of ME/CFS prevalence within the LC population is of cardinal importance to optimal allocation of resources and better design of healthcare interventions to manage and treat patients with this devastating disease.

Source: Anna D. Grabowska, Francisco Westermeier, Luís Nacul, Eliana Lacerda, Nuno Sepúlveda. The importance of estimating prevalence of ME/CFS in future epidemiological studies of long COVID. DOI:10.13140/RG.2.2.20997.52967 https://www.researchgate.net/publication/373043778_The_importance_of_estimating_prevalence_of_MECFS_in_future_epidemiological_studies_of_long_COVID (Full text)

Contesting oppressive regimes of truth: A critical feminist re-examination of (bio)psychosocial hegemony in the field of myalgic encephalomyelitis / chronic fatigue syndrome

Abstract:

Myalgic encephalomyelitis / chronic fatigue syndrome, a disabling condition disproportionately affecting women, is predominantly clinically managed through a (bio)psychosocial lens with psychosocial-inspired therapies, criticised for facilitating social and epistemic injustice, psychological and physical harms. Whilst most literature contesting (bio)psychosocial practices espouses a mainstream scientific perspective, politics and power relations undergirding psychosocial hegemony are better explicated through a critical lens. This article re-examines the ascendancy of psychosocial therapies and related practices through a critical feminist psychology and Foucauldian lens, with a view to locating oppressive practices in their socio-political and cultural context and promoting dialogue on possibilities for positive social change.

Source: Hunt, J. E. (2023, August 10). Contesting oppressive regimes of truth: A critical feminist re-examination of (bio)psychosocial hegemony in the field of myalgic encephalomyelitis / chronic fatigue syndrome. https://doi.org/10.31235/osf.io/3g7kp https://osf.io/preprints/socarxiv/3g7kp/ (Full text)

Chronic inflammation, neuroglial dysfunction, and plasmalogen deficiency as a new pathobiological hypothesis addressing the overlap between post-COVID-19 symptoms and myalgic encephalomyelitis/chronic fatigue syndrome

Highlights:

  • Plasmalogens (Pls) are lipids containing a vinyl-ether bond in their glycerol backbone.
  • Pls have antioxidant properties and are important for curved membrane assemblies.
  • Post-COVID-19 symptoms are highly prevalent and share several features with ME/CFS.
  • Pls depletion is a shared biological hallmark of ME/CFS and acute COVID-19 syndrome.
  • Pls replacement is a promising tool against neuroinflammation in these two conditions.

Abstract:

After five waves of coronavirus disease 2019 (COVID-19) outbreaks, it has been recognized that a significant portion of the affected individuals developed long-term debilitating symptoms marked by chronic fatigue, cognitive difficulties (“brain fog”), post-exertional malaise, and autonomic dysfunction. The onset, progression, and clinical presentation of this condition, generically named post-COVID-19 syndrome, overlap significantly with another enigmatic condition, referred to as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Several pathobiological mechanisms have been proposed for ME/CFS, including redox imbalance, systemic and central nervous system inflammation, and mitochondrial dysfunction. Chronic inflammation and glial pathological reactivity are common hallmarks of several neurodegenerative and neuropsychiatric disorders and have been consistently associated with reduced central and peripheral levels of plasmalogens, one of the major phospholipid components of cell membranes with several homeostatic functions.

Of great interest, recent evidence revealed a significant reduction of plasmalogen contents, biosynthesis, and metabolism in ME/CFS and acute COVID-19, with a strong association to symptom severity and other relevant clinical outcomes. These bioactive lipids have increasingly attracted attention due to their reduced levels representing a common pathophysiological manifestation between several disorders associated with aging and chronic inflammation. However, alterations in plasmalogen levels or their lipidic metabolism have not yet been examined in individuals suffering from post-COVID-19 symptoms.

Here, we proposed a pathobiological model for post-COVID-19 and ME/CFS based on their common inflammation and dysfunctional glial reactivity, and highlighted the emerging implications of plasmalogen deficiency in the underlying mechanisms. Along with the promising outcomes of plasmalogen replacement therapy (PRT) for various neurodegenerative/neuropsychiatric disorders, we sought to propose PRT as a simple, effective, and safe strategy for the potential relief of the debilitating symptoms associated with ME/CFS and post-COVID-19 syndrome.

Source: Adriano Maia Chaves-Filho, Olivia Braniff, Angelina Angelova, Yuru Deng, Marie-Ève Tremblay. Chronic inflammation, neuroglial dysfunction, and plasmalogen deficiency as a new pathobiological hypothesis addressing the overlap between post-COVID-19 symptoms and myalgic encephalomyelitis/chronic fatigue syndrome. Brain Research Bulletin, Volume 201, September 2023, 110702. https://www.sciencedirect.com/science/article/pii/S0361923023001272 (Full text)

Consequences of sarcolemma fatigue on maximal muscle strength production in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Highlights:

  • Does force failure result from sarcolemma fatigue in Myalgic Encephalomyelitis patients?
  • Two groups of Myalgic Encephalomyelitis patients with or not M wave alterations were compared.
  • Maximal handgrip strength and M wave in forearm muscle were simultaneously measured.
  • Post-exercise changes in Maximal handgrip strength and M wave were positively correlated.
  • The post exercise sarcolemma fatigue measured could be the cause of muscle failure in these patients.

Background: Myalgic encephalomyelitis is an invalidating chronic disease often associated with exercise-induced alterations of muscle membrane excitability (M wave). No simultaneous measurements of maximal isometric force production and sarcolemma fatigue in the same muscle group have been previously reported. We hypothesized that M wave alterations could be partly responsible for the reduced muscle force present in this invalidating disease.

Methods: This retrospective study compared two groups of patients who presented (n = 30) or not (n = 28) alterations of M waves evoked by direct muscle stimulation during and after a cycling exercise bout. The maximal handgrip strength was measured before and after exercise, concomitantly with electromyogram recordings from flexor digitorum longus muscle. The patients also answered a questionnaire to identify eventual exacerbation of their clinical symptoms following the exercise test.

Findings: The M wave amplitude significantly decreased in muscles and the M wave duration significantly increased in the group of patients with M wave alterations after exercise. Resting values of handgrip were significantly lower in patients with exercise-induced M-wave alterations than in patients without M-wave abnormalities. In patients with exercise-induced M-wave alterations, handgrip significantly decreased after exercise and the changes in handgrip and M wave were positively correlated. The frequency of post-exertion malaise, increased fatigue, myalgia, headache and cognitive dysfunction was significantly higher in patients with M-wave alterations and variations in handgrip after exercise.

Interpretation: These data suggest that post-exercise sarcolemma fatigue often measured in patients with myalgic encephalomyelitis could be the cause of muscle failure.

Source: Frédérique Retornaz, Chloé Stavris, Yves Jammes. Consequences of sarcolemma fatigue on maximal muscle strength production in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Clinical Biomechanics, Volume 108, August 2023, 106055. https://www.sciencedirect.com/science/article/pii/S0268003323001869 (Full text)

DNA methylation signatures of functional somatic syndromes: Systematic review

Abstract:

Objective: Functional somatic syndromes (FSS) are highly prevalent across all levels of healthcare. The fact that they are characterised by medically unexplained symptoms, such as fatigue and pain, raises the important question of their underlying pathophysiology. Psychosocial stress represents a significant factor in the development of FSS and can induce long-term modifications at the epigenetic level. The aim of this review was to systematically review, for the first time, whether individuals with FSS are characterised by specific alterations in DNA methylation.

Methods: MEDLINE and PsycINFO were searched from the first available date until September 2022. The inclusion criteria were: 1) adults fulfilling research diagnostic criteria for chronic fatigue syndrome, fibromyalgia syndrome, and/or irritable bowel syndrome, 2) healthy control group, and 3) candidate-gene or genome-wide study of DNA methylation.

Results: Sixteen studies (N = 957) were included. In candidate-gene studies, specific sites within NR3C1 were identified, which were hypomethylated in individuals with chronic fatigue syndrome compared to healthy controls. In genome-wide studies in chronic fatigue syndrome, a hypomethylated site located to LY86 and hypermethylated sites within HLA-DQB1 were found. In genome-wide studies in fibromyalgia syndrome, differential methylation in sites related to HDAC4 , TMEM44 , KCNQ1 , SLC17A9 , PRKG1 , ALPK3 , TFAP2A , and LY6G5C was found.

Conclusions: Individuals with chronic fatigue syndrome and fibromyalgia syndrome appear to be characterised by altered DNA methylation of genes regulating cellular signalling and immune functioning. In chronic fatigue syndrome, there is preliminary evidence for these to be implicated in key pathophysiological alterations, such as hypocortisolism and low-grade inflammation, and to contribute to the debilitating symptoms these individuals experience.

Preregistration PROSPERO identifier: CRD42022364720.

Source: Fischer S, Kleinstäuber M, Fiori LM, Turecki G, Wagner J, von Känel R. DNA methylation signatures of functional somatic syndromes: Systematic review. Psychosom Med. 2023 Aug 21. doi: 10.1097/PSY.0000000000001237. Epub ahead of print. PMID: 37531610. https://pubmed.ncbi.nlm.nih.gov/37531610/

In severe first episode major depressive disorder, psychosomatic, chronic fatigue syndrome, and fibromyalgia symptoms are driven by immune activation and increased immune-associated neurotoxicity.

Abstract:

Background: Major depressive disorder (MDD) is accompanied by activated neuro-immune pathways, increased physiosomatic and chronic fatigue-fibromyalgia (FF) symptoms. The most severe MDD phenotype, namely major dysmood disorder (MDMD), is associated with adverse childhood experiences (ACEs) and negative life events (NLEs) which induce cytokines/chemokines/growth factors.

Aims: To delineate the impact of ACE+NLEs on physiosomatic and FF symptoms in first episode (FE)-MDMD, and examine whether these effects are mediated by immune profiles.

Methods: ACEs, NLEs, physiosomatic and FF symptoms, and 48 cytokines/chemokines/growth factors were measured in 64 FE-MDMD patients and 32 normal controls.

Results: Physiosomatic, FF and gastro-intestinal symptoms belong to the same factor as depression, anxiety, melancholia, and insomnia. The first factor extracted from these seven domains is labeled the physio-affective phenome of depression. A part (59.0%) of the variance in physiosomatic symptoms is explained by the independent effects of interleukin (IL)-16 and IL-8 (positively), CCL3 and IL-1 receptor antagonist (inversely correlated). A part (46.5%) of the variance in physiosomatic (59.0%) symptoms is explained by the independent effects of interleukin (IL)-16, TNF-related apoptosis-inducing ligand (TRAIL) (positively) and combined activities of negative immunoregulatory cytokines (inversely associated).

Partial Least Squares analysis shows that ACE+NLEs exert a substantial influence on the physio-affective phenome which are partly mediated by an immune network composed of interleukin-16, CCL27, TRAIL, macrophage-colony stimulating factor, and stem cell growth factor.

Conclusions: The physiosomatic and FF symptoms of FE-MDMD are partly caused by immuneassociated neurotoxicity due to Th-1 polarization, T helper-1, and M1 macrophage activation and relative lowered compensatory immunoregulatory protection.

Source: Michael Maes, Abbas F Almulla, Bo Zhou, Ali Abbas Abo Algon, Pimpayao Sodsai. In severe first episode major depressive disorder, psychosomatic, chronic fatigue syndrome, and fibromyalgia symptoms are driven by immune activation and increased immune-associated neurotoxicity. ResearchGate [Preprint] https://www.researchgate.net/publication/372940821_In_severe_first_episode_major_depressive_disorder_psychosomatic_chronic_fatigue_syndrome_and_fibromyalgia_symptoms_are_driven_by_immune_activation_and_increased_immune-associated_neurotoxicity (Full text)

The demographic features of fatigue in the general population worldwide: a systematic review and meta-analysis

Abstract:

Background: Fatigue is one of the most common subjective symptoms that impairs daily life and predict health-related events. This study aimed to estimate the prevalence of fatigue in the global population.

Methods: PubMed and the Cochrane Library were used to search for relevant articles from inception to December 31, 2021. Studies with prevalence data of fatigue in the general population were selected and reviewed by three authors independently and cross-checked. Regarding subgroups, adults (≥18 years), minors (<18 years), and specific occupation population (participants in each study being limited to a specific occupational group), and fatigue types and severity, meta-analysis was conducted to produce point estimates and 95% confidence intervals (95% CI).

Results: From the initial 3,432 studies, 91 studies accounting for 115 prevalence data points (623,624 participants) were finally selected. The prevalence of general fatigue (fatigue lasting < 6 months, or fatigue of unspecified duration) was 20.4% (95% CI, 16.7–25.0) in adults, 11.7% (95% CI, 5.2–26.6) in minors, and 42.3% (95% CI, 33.0–54.2) in specific occupations. Chronic fatigue (fatigue lasting more than 6 months) affected 10.1% (95% CI, 8.2–12.5) of adults, 1.5% (95% CI, 0.5–4.7) of minors, and 5.5% (95% CI, 1.4–21.6) of subjects in specific occupations. There was an overall female-predominant prevalence for all subgroup analyses, with a total odds ratio of 1.4 (95% CI, 1.3–1.6).

Regarding the severity and presence of medical causes, the total prevalence of moderate fatigue [14.6% (95% CI, 9.8–21.8)] was 2.4-fold that of severe fatigue [6.1% (95% CI, 3.4–11.0)], while unexplained fatigue (fatigue experienced by individuals without any underlying medical condition that can explain the fatigue) was ~2.7-fold that of explained fatigue (fatigue experienced by individuals with a medical condition that can explain the fatigue); as proportion of 40.0% of physical, 8.6% of mental, and 28.4% of mixed cause.

Conclusions: This study has produced the first comprehensive picture of global fatigue prevalence in the general population, which will provide vital reference data contributing to fatigue-related research, including the prevention of diseases.

Source: Yoon JH, Park NH, Kang YE, Ahn YC, Lee EJ, Son CG. The demographic features of fatigue in the general population worldwide: a systematic review and meta-analysis. Front Public Health. 2023 Jul 28;11:1192121. doi: 10.3389/fpubh.2023.1192121. PMID: 37575103; PMCID: PMC10416797. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10416797/ (Full text)

Long COVID, POTS, CFS and MTHFR: Linked by Biochemistry and Nutrition

Abstract:

The recent pandemic has energized research spotlighting chronic fatigue disorders. The similarities between Long COVID (LC) and Chronic Fatigue Syndrome (CFS), often accompanied by postural orthostatic tachycardia syndrome (POTS) are striking.

Furthermore, the majority afflicted with LC and CFS may be those with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, present in the majority of Americans and characterized by hypomethylation. Elevated homocysteine (Hcy) and depressed B9 and B12 may be links. Speculation about an association between these laboratory analytes and MTHFR abnormalities has been previously reported (Regland et al., 2015).

The absence of a blood-brain barrier (BBB) in CNS circumventricular organs (CVOs) that control autonomic and neuroendocrine functions, problematic in LC, CFS, POTS, and MTHFR, is provocative. Diffusion of CNS Hcy is associated with brain fog, cognitive impairment, and dementia. This provides a distinct link between MTHFR variants and the fog of LC, CFS, and POTS.

Small intestine bacterial overgrowth (SIBO), present in about 17% of Americans, is linked to POTS, mast cell activation syndrome (MCAS), and Ehlers Danlos syndrome (EDS). All exhibit histamine intolerance and female predominance. This may be due to hypomethylation and/or intestinal diamine oxidase (DAO) deficiency.

Metabolism of monoamines and histamine requires methylation. Specific CNS nuclei in CVOs may also provide insight to the POTS paradox. The similar gut microbiomes of LC/CFS (and vitamin D deficiency) may via CVOs trigger an imbalance in glutamate/GABA neurotransmission that translates to neuroendocrine and baroreflex dysfunction. Homozygosity for the MTHFR 677T allele can facilitate hypermethylation via an alternative “rescue” riboflavin pathway triggered by significant Hcy increase.

Hypermethylation predominates in Long Covid. The primary problem in these syndromes is compromised mitochondrial function due to oxidative stress induced by an antioxidant shortfall.

Victims are also frequently deficient in 25(OH)D3 (the storage form of vitamin D), magnesium, and B vitamins, consumed by the persistent chronic inflammatory state. Estrogen increases histamine, norepinephrine, and bradykinin (BKN), which may in part explain the brain fog and its predilection for females.

Source: Patrick W Chambers. Long COVID, POTS, CFS and MTHFR: Linked by Biochemistry and Nutrition. Journal of Orthomolecular Medicine. 38. https://www.researchgate.net/publication/373073968_Long_Covid_POTS_CFS_and_MTHFR_Linked_by_Biochemistry_and_Nutrition#fullTextFileContent (Full text)

eLearning improves allied health professionals’ knowledge and confidence to manage medically unexplained chronic fatigue states: A randomized controlled trial

Abstract:

Objectives: To evaluate the impact of eLearning by allied health professionals on improving the knowledge and confidence to manage people with medically unexplained chronic fatigue states (FS).

Methods: Using a parallel randomized controlled trial design, participants were randomized 1:1 to a 4-week eLearning or wait-list control group. Knowledge and self-reported confidence in clinical skills to implement a therapeutic intervention for patients with FS were assessed at baseline, post-intervention and follow-up. Secondary outcomes (adherence and satisfaction with online education, knowledge retention) were also assessed. Data was analyzed using intention-to-treat.

Results: There were 239 participants were randomized (eLearning n = 119, control n = 120), of whom 101 (85%) eLearning and 107 (89%) control participants completed baseline assessments and were included in the analysis. Knowledge (out of 100) improved significantly more in the eLearning group compared to the control group [mean difference (95% CI) 8.6 (5.9 to 11.4), p < 0.001]. Knowledge was reduced in the eLearning group at follow-up but was still significantly higher than baseline [6.0 (3.7 to 8.3), p < 0.001]. Median change (out of 5) in confidence in clinical skills to implement the FS intervention was also significantly greater in the eLearning group compared to the control group [knowledge: eLearning (1.2), control (0); clinical skills: eLearning (1), control (0.1); both p < 0.001)]. Average time spent on the eLearning program was 8.8 h. Most participants (80%) rated the lesson difficulty as at the “right level”, and 91% would recommend it to others.

Conclusions: eLearning increased knowledge and confidence to manage FS amongst allied health professionals and was well-accepted.

Registration: ACTRN12616000296437 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370222&isReview=true.

Source: Jones MD, Casson SM, Barry BK, Li SH, Valenzuela T, Cassar J, Lamanna C, Lloyd AR, Sandler CX. eLearning improves allied health professionals’ knowledge and confidence to manage medically unexplained chronic fatigue states: A randomized controlled trial. J Psychosom Res. 2023 Aug 16;173:111462. doi: 10.1016/j.jpsychores.2023.111462. Epub ahead of print. PMID: 37619433. https://www.sciencedirect.com/science/article/pii/S0022399923003197 (Full text)

Postacute sequelae of COVID-19 at 2 years

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection. We built a cohort of 138,818 individuals with SARS-CoV-2 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs and followed them for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of COVID-19 (PASC) according to care setting during the acute phase of infection.

The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the 2 years in hospitalized individuals. Within the 80 prespecified sequelae, 69% and 35% of them became not significant at 2 years after infection among nonhospitalized and hospitalized individuals, respectively.

Cumulatively at 2 years, PASC contributed 80.4 (95% confidence interval (CI): 71.6-89.6) and 642.8 (95% CI: 596.9-689.3) disability-adjusted life years (DALYs) per 1,000 persons among nonhospitalized and hospitalized individuals; 25.3% (18.9-31.0%) and 21.3% (18.2-24.5%) of the cumulative 2-year DALYs in nonhospitalized and hospitalized were from the second year.

In sum, while risks of many sequelae declined 2 years after infection, the substantial cumulative burden of health loss due to PASC calls for attention to the care needs of people with long-term health effects due to SARS-CoV-2 infection.

Source: Bowe B, Xie Y, Al-Aly Z. Postacute sequelae of COVID-19 at 2 years. Nat Med. 2023 Aug 21. doi: 10.1038/s41591-023-02521-2. Epub ahead of print. PMID: 37605079. https://www.nature.com/articles/s41591-023-02521-2 (Full text)