Category: Overview

Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness often triggered by an initiating acute event, mainly viral infections. The transition from acute to chronic disease remains unknown, but interest in this phenomenon has escalated since the COVID-19 pandemic and the post-COVID-19 illness, termed ‘long COVID’ (LC). Both ME/CFS and LC share many clinical similarities.

Here, we present recent findings in ME/CFS research focussing on proposed disease pathologies shared with LC. Understanding these disease pathologies and how they influence each other is key to developing effective therapeutics and diagnostic tests. Given that ME/CFS typically has a longer disease duration compared with LC, with symptoms and pathologies evolving over time, ME/CFS may provide insights into the future progression of LC.

Source: Annesley SJ, Missailidis D, Heng B, Josev EK, Armstrong CW. Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies. Trends Mol Med. 2024 Mar 4:S1471-4914(24)00028-5. doi: 10.1016/j.molmed.2024.02.003. Epub ahead of print. PMID: 38443223. https://www.sciencedirect.com/science/article/pii/S1471491424000285 (Full text)

Post Viral Pain, Fatigue, and Sleep Disturbance Syndromes: Current knowledge and Future Directions

Abstract:

Post-viral pain syndrome, also known as post-viral syndrome (PVS), is a complex condition characterized by persistent pain, fatigue, musculoskeletal pain, neuropathic pain, neurocognitive difficulties, and sleep disturbances1,2 that can occur after an individual has recovered from a viral infection. Much remains unknown regarding the pathophysiology of post-viral syndromes and few studies have provided a comprehensive summary of the condition, agents that cause it, and successful treatment modalities.

With the COVID-19 pandemic continuing to affect millions of people worldwide, the need for understanding the etiology of post-viral illness and how to help individuals cope with the sequalae is paramount.2 This narrative review provides a summary of the sequelae of post-viral syndromes, viral agents that cause it, the pathophysiology, treatment, and future considerations for research and targeted therapies.

Source: Caleb Tackey, P. Maxwell Slepian, Hance Clarke & Nimish Mittal (2023) Post Viral Pain, Fatigue, and Sleep Disturbance Syndromes: Current knowledge and Future Directions, Canadian Journal of Pain, DOI: 10.1080/24740527.2023.2272999 https://www.tandfonline.com/doi/full/10.1080/24740527.2023.2272999 (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Me/Cfs): The Biology of a Neglected Disease

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease with debilitating symptoms that impact all aspects of life. The diverse symptom presentation indicates that ME/CFS is likely to have a multifactorial origin. However, it is an extremely understudied disease with no standardised diagnostic criteria or proven treatment avenues. It is hypothesised that environmental insults (such as acute infection, mainly viral) or stress in genetically susceptible individuals may trigger the development of ME/CFS.

These insults result in acute inflammatory responses, along with aberrant immune activation. A spiralling disruption of homeostasis promotes subsequent patho-mechanisms including gut dysbiosis and systemic inflammation, and eventually a pathological clotting system, chronic endothelialitis, vasoconstriction, and hypoxia. Additionally, dysfunctional energy metabolism including oxidative stress is also present in the development of ME/CFS. Since the exact pathophysiology of ME/CFS remains unclear, additional research is required to reveal further insight into this “neglected” disease.

Source: Arron, Hayley and Marsh, Benamin and Khan, M. Asad and Jaeger, Beate and Kell, Douglas and Pretorius, Etheresia, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Me/Cfs): The Biology of a Neglected Disease. Available at SSRN: https://ssrn.com/abstract=4622074 or http://dx.doi.org/10.2139/ssrn.4622074 (Full text available as PDF file)

Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic neurologic disease often preceded by infection. There has been increased interest in ME/CFS recently because of its significant overlap with the post-COVID syndrome (long COVID or post-acute sequelae of COVID), with several studies estimating that half of patients with post-COVID syndrome fulfill ME/CFS criteria. Our concise review describes a generalist approach to ME/CFS, including diagnosis, evaluation, and management strategies.

Source: Grach SL, Seltzer J, Chon TY, Ganesh R. Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Mayo Clin Proc. 2023 Oct;98(10):1544-1551. doi: 10.1016/j.mayocp.2023.07.032. PMID: 37793728. https://www.mayoclinicproceedings.org/article/S0025-6196(23)00402-0/fulltext (Full text)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A preliminary survey among patients in Switzerland

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multi-factorial systemic chronic debilitating disease of poorly understood etiology and limited systematic evidence. The questionnaire and interview-based survey included 169 ME/CFS patients from the Swiss ME/CFS association. The majority of patients were females (72.2%), single (55.7%) and without children (62.5%). Only one third were working (full/part-time). The mean onset of ME/CFS was 31.6 years of age with 15% of patients being symptomatic before their 18th birthday.

In this cohort, patients had documented ME/CFS for a mean 13.7 years, whereby half (50.3%) stated their condition was progressively worsening. Triggering events and times of disease onset were recalled by 90% of the participants. An infectious disease was associated with a singular or part of multiple events by 72.9% and 80.6%, respectively.

Prior to disease onset, a third of the patients reported respiratory infections; followed by gastro-intestinal infections (15.4%) and tick-borne diseases (16.2%). Viral infections were recalled by 77.8% of the respondents, with Epstein Barr Virus being the most commonly reported agent. Patients self-reported an average number of 13 different symptoms, all described specific triggers of symptoms exacerbation and 82.2% suffered from co-morbidities.

This study collated clinically relevant information on ME/CFS patients in Switzerland, highlighting the extent of disease severity, the associated factors negatively affecting daily life activities and work status as well as potential socio-economic impact.

Source: Rea Tschopp; Rahel S. König; Protazy Rejmer; Daniel H. Paris. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A preliminary survey among patients in Switzerland. Heliyon, Volume 9, Issue 5, e15595, May 2023. https://www.cell.com/heliyon/fulltext/S2405-8440(23)02802-5 (Full text)

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.

Source: Tate WP, Walker MOM, Peppercorn K, Blair ALH, Edgar CD. Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID. International Journal of Molecular Sciences. 2023; 24(6):5124. https://doi.org/10.3390/ijms24065124 (Full text)

Myalgic Encephalitis/Chronic Fatigue Syndrome: Diagnostic and Therapeutic Approach and Biological Research

Abstract:

Myalgic encephalitis/chronic fatigue syndrome, an intractable disease characterized by profound fatigue, sleep disturbance, cognitive impairment, and orthostatic intolerance, among other features, often occurs after infectious episodes. Patients experience various types of chronic pain; however, post-exertional malaise is the most significant feature, which requires pacing. In this article, I summarize the current diagnostic and therapeutic approaches and describe recent biological research in this domain.

Source: Sato W. [Myalgic Encephalitis/Chronic Fatigue Syndrome: Diagnostic and Therapeutic Approach and Biological Research]. Brain Nerve. 2023 Mar;75(3):217-225. Japanese. doi: 10.11477/mf.1416202311. PMID: 36890757. https://pubmed.ncbi.nlm.nih.gov/36890757/ [Article in Japanese]

Current knowledge about Chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME) causes – summary

Abstract:

Chronic Fatigue Syndrome (CFE) is a severe and disabling disease whose etiology has not yet been elucidated. This implies the lack of a specific biomarker for the diagnosis of PE, and no causal treatment.

There are a number of diagnostic criteria that facilitate the diagnosis of PE, but it is still a diagnosis with exclusion. This chapter reviews the scientific literature systematically, summarizing the available knowledge about the probable etiology of Chronic Fatigue Syndrome.

The current topic of the influence of SARS-Cov-2 virus infection on the development of symptoms of IPC was also taken into account in particular.

A clear explanation of the etiology of PE is necessary for the further development of scientific knowledge about the Chronic Fatigue Syndrome.

Source: PRYLIŃSKA-JAŚKOWIAK, Monika & KOŻUCHOWSKI, Marcin. Current knowledge about Chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME) causes – summary. Journal of Education, Health and Sport [online]. 13 September 2022, T. 12, nr 9, s. 712–719. [accessed 26.9.2022]. DOI 10.12775/JEHS.2022.12.09.084.  https://apcz.umk.pl/JEHS/article/view/39954 https://apcz.umk.pl/JEHS/article/view/39954/33214 (Full text)

Understanding myalgic encephalomyelitis

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe condition characterized by post-exertional neuroimmune exhaustion (PENE) accompanied by neurological, immunological, gastrointestinal (GI), and mitochondrial disturbances (1). The global prevalence of ME/CFS is ∼1%, affecting 17 million to 24 million people (2). ME/CFS is heterogeneous not only in symptom presentation but also illness trajectories, which can be worsening, plateauing, improving, or relapsing-remitting. Approximately 25% of patients with ME/CFS are considered severe and are bound to their homes. Although the etiology of ME/CFS is elusive, a large proportion of patients (∼60%) report post-infectious onset, such as after Epstein-Barr virus infection (3). The recent emergence of a chronic post-infectious condition, called Long Covid, overlaps considerably with ME/CFS in immunological, mitochondrial, and neurological dysfunctions (4). These similarities have resulted in increased interest and acceptance of ME/CFS as a disease and may stimulate research, the development of a diagnostic test, and pharmacotherapeutic interventions in ME/CFS that may be applied to Long Covid.

Read the rest of this article HERE.

Source: Sonya Marshall-Gradisnik and Natalie Eaton-Fitch. Understanding myalgic encephalomyelitis. SCIENCE, 8 Sep 2022, Vol 377, Issue 6611, pp. 1150-1151, DOI: 10.1126/science.abo126 https://www.science.org/doi/10.1126/science.abo1261 (Full text)

Special Issue “Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment”

Introduction:
Chronic fatigue syndrome, or myalgic encephalomyelitis (CFS/ME), is a debilitating disease with unknown causes that is more common in women and tends to develop between patients’ mid-20s and mid-40s. From the perspectives on the etiology and pathophysiology, CFS/ME has been labeled differently, which has influenced changes in case definitions and terminologies. CFS/ME is characterized by persistent asthenia with associated musculoskeletal pain, cognitive disturbance (including attention, memory, and concentration), psychological troubles (depression, anxiety), sleep disorders, and a variety of neurovegetative symptoms. The best appropriate therapeutic is an integrative approach, based on a personalized medical plane that includes distinct groups of procedures: educational, cognitive-behavioral, pharmacological and non-pharmacological such as occupational therapy and rehabilitation. CFS/ME has some common clinical features with fibromyalgia, and a differential diagnosis is difficult for General Practitioners (GPs) [1,2].
The recent opinion is that CFS/ME pathogenesis is dependent on several factors or causes. Different studies have shown evidence for an alteration in immunity system in patients with CFS/ME. A modification in cytokine subsets, a diminished activity of natural killer (NK) lymphocytes, the detection of autoantibodies and a decreased response of T cells to mitogens and specific antigens have been observed. An increased level of pro-inflammatory cytokines may explain some of the clinical features, such as fatigue and flulike symptoms, with an effect on NK activity. Anomalous activation of the T lymphocyte profile and a reduction in antibody-dependent cell-mediated cytotoxicity have been reported. An increased number of CD8+ cytotoxic T lymphocytes and CD38 and HLA-DR activation markers have been demonstrated, and a reduced CD11b expression associated with an increased expression of CD28+ T subsets has been described [3]. An interest towards CFS/ME is increased with the recent pandemic by SARS-CoV-2 because, after the acute phase of disease, some patients have clinical features similar to CFS/ME called Long-COVID, characterized by tiredness, brain fog and headache. There is debate on common aspect between these pathologies but in especially a possible effect of COVID-19 on CFS/ME and the consequences [4].
This Special Issue on CFS/ME collects 18 papers with an interdisciplinary view on the current demographic and epidemiological data and immunological characteristics of CFS/ME and examines the different pathogenic hypotheses, as well as giving information about the latest knowledge on diagnostic investigations, pharmacological, integrative, physical, cognitive-behavioral and psychological curative approaches.
It is known that CFS/ME affects young adults, but there are little studies in pediatric and adolescent age. Australian colleagues Elisha K. Josev and colleagues have carried out a case-controlled follow-up study on the health, wellbeing and prognosis of Australian adolescents with CFS/ME on the comprehension of the important relation between physical and psychological health factors to adolescent’ long-term outcome for approaching future prevention, management and treatment [5]. Concerning epidemiological data, there is little information for Asian countries such Korea and Japan. Eun-Jn Lim and Chang-Gue Son evaluate and match the prevalence of CFS/ME in Korea and Japan, performing a meta-analysis analyzing the main characteristics of these nations [6].
The emerging data of the involvement of immune system confirmed the hypothesis that CFS/ME is an autoimmune disease; recent studies have shown the role of autoantibodies towards the vegetative nervous system. Freitag H. and colleagues reported the reactivity of autoantibodies to vasoregulative G-Protein-Coupled Receptor correlates with autonomic dysfunction, clinical gravity and disability in CFS/ME patients [7]. Another paper, by Kujawski S. and collaborators, studies the differences in CFS patients applying post-exertional malaise (PEM) as indicators of aortic stiffness, autonomic nervous system function and severity of fatigue [8]. Always on the role of the autonomic nervous system dysfunction, Jessica Van Oosterwijck et al. published a paper showing decreased parasympathetic reactivation from physical exercise that could be correlated with a bad prognosis or high risk for adverse cardiac event [8]. Varesi A. and colleagues investigated the emerging role of the modified composition of gut microbiota in relationship with genetic, infection, immunological and other influences that have seen in CFS/ME individuals [9]. The authors discuss the change and the potential therapeutic application of treating the gut in CFS/ME patients [10].
A collection of papers investigates the importance of the diagnostic tools in clinical practice. We start with Baklund H. I. et al., who evaluated the blood test in relationship with clinical features and diagnostic classification, suggesting muscle damage and metabolic abnormalities [11].
A potential blood diagnostic tool, by Castro-Marrero J. and his Spanish collaborators, could be the complement C1 examining in CFS/ME three-symptom clusters, identified as severe, moderate and mild, presenting important differences in five blood parameters [12]. Another objective measurement for PEM, which is a hallmark of CFS/ME, is the application of the two-days cardiopulmonary exercise test (CPET) to assess functional impairment: Eun-Jin Lim and Korean collaborators, in their paper, published the results of a meta-analysis on this diagnostic tool [13]. Moreover, Do-Young Kim and his Korean colleagues examined a systematic review to provide an overview of the adoption of the main measurements in RCTs for CFS/ME. Around 40% of RCTs utilized multiple primary measurements. This information could be helpful in clinical practice in the design of medical studies for CFS/ME-linked therapeutic development [14].
The therapy of CFS/ME is problematic due to lack of knowledge on the etiopathogenesis of this disease, with application of the unconventional and conventional treatments: Tirelli and colleagues compared the application of oxygen–ozone autohemotherapy (O2-O3-AHT) in male vs. female patients, evaluating the differences in their responses to this approach [15]. The effects of exercise from a structured activity program have been disputed; Kujawski S. et al., with a multidisciplinary study, examined the impact of a personalized program of activities associated with cardiovascular, mitochondrial and fatigue parameters, showing a reduction in fatigue and an improving functional performance [16]. An important conventional therapeutic approach is the effect of s.c. IgG self-treatment in ME/CFS patients with IgG/IgG subgroup deficiency. The aim of Scheibenbogen C. and her German collaborators was to study the IgG administration for its immunomodulatory effects. [17].
There are few studies relationship CFS/ME patients and COVID-19 patients [18]. Araja D. and Latvian collaborators researched undiagnosed CFS/ME patients, hypothesizing the expansion of post-viral CFS as an effect of COVID-19 and its social impact. The Latvian research results show that patients with CFS/ME are not a risk group for COVID-19; however, COVID-19 causes symptoms similar to CFS/ME. They concluded that CFS/ME creates a significant social consequence, considering the direct medical costs of undiagnosed patients. At the same time, COVID-19 is responsible for long-lasting complications and a chronic course, such as post-viral CFS [19].
Deumer U-S et al. discuss the role of the gut microbiota on disease progression, highlighting a potential biomarker in non-coding RNA (ncRNA) as a probable diagnostic tool and suggesting the possibility that SARS-CoV-2 infection may result in symptoms similar to CFS [20].
CFS/ME has an overlap with Fibromyalgia, and differential diagnosis is difficult for some clinicians because the diagnosis of fibromyalgia is based only on clinical features that are characterized by widespread pain, fatigue, stiffness and troubles in cognitive functions, such as attention, executive function and verbal memory deficits [21]. It is important to add more tests beyond the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) test in fibromyalgia patients to assess the relationship between physical and cognitive performance, as reported by Murillo-Garcia A. and colleagues [22]. Another potential diagnostic tool is studied by Martin-Brufau R. and collaborators using electroencephalography for patients with fibromyalgia that present lower levels of brain activity with reduced connectivity than controls. The Spanish group identified a possible neurophysiological pattern that could adapt to the clinical features of the disease [23]. The therapeutic approach to this disease is a difficult choice. Rodriguez-Mansilla J. and Spanish collaborators studied the effects of non-pharmacological treatment in terms of the effectiveness of an exercise program compared to wellness activities by improving pain, flexibility, static balance, perceived effort and quality of life in patients with fibromyalgia. Participants in the active exercise program performed better than exercise for well-being [24]. This proposal in fibromyalgia is associated with other conventional treatments based on a multidisciplinary approach.
In conclusion, the papers published within this research topic, with the major contribution of the members of the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE), give us the recent highlight perspective and opportunities for the discovery and development of possible specific biomarkers, diagnostic and therapeutic approaches for these immunological disorders.
Source: Lorusso L, Ricevuti G. Special Issue “Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment”. J Clin Med. 2022 Aug 4;11(15):4563. doi: 10.3390/jcm11154563. PMID: 35956178. https://www.mdpi.com/2077-0383/11/15/4563/htm (Full text)