The weekly research round-up includes recent publications about ME/CFS and Long Covid. We highlight the studies that have particularly caught our interest and follow these with the full list of publications together with their abstracts (summaries).
RESEARCH INDEX
The ME Association maintains a comprehensive index of published research on ME/CFS and Long Covid that is free to use and updated weekly.
Audio Commentary by Dr Katrina Pears
ME/CFS Research Published 21 – 27 March 2023
It’s been another busy week for research with seven new ME/CFS studies but eighteen new Long Covid studies.
We’ve seen a mix of research this week but no strong biomedical studies, several of the studies covering both ME/CFS and Long Covid (Papers two (2) and three (3)), while papers four (4), six (6) and seven (7) cover Fibromyalgia, multiple sclerosis and Primary mitochondrial myopathies (PMM), retrospectively.
We have highlighted one of the ME/CFS studies in more detail below:
Paper one (1) is a review article which covers the following specific topics : cardiovascular (including heart, vessels, orthostatic intolerance, cerebral blood flow, endothelium dysfunction), haematological (including blood cells and proteins) and then reviews the role of viruses, including herpesvirus.
This review provides a summary of the evidence we know on these topics, which are either the causes or consequences of having ME/CFS. The authors focus and outline the detail from a few specific studies, however, the evidence presented is of course limited by the research done to date. The review brings together findings from ME/CFS and Long Covid.
The section on the role of viruses and their reactivation brings findings in the cardiovascular system together, which is worth a read, with Figure 2 linking different systems together. We have previously written a research summary on the reactivation of human herpesvirus (see here).
It should also be noted that there is a strong focus on the role of hypercoagulability and platelet hyperactivation (i.e. microclots), at the moment the evidence for this in ME/CFS is lacking and controversial. This hypothesis is also postulated in viral activity. One of the authors from this review, has been pivotal in the Long Covid microclot research (e.g. Pretorious et al., 2021a; Pretorious et al., 2021b). Furthermore, neurological findings do not have their own section in this review it is suggested that the autonomic branch of the nervous system causes cardiovascular dysfunction.
Unfortunately, this review is not a particularly easy read to gain insight into the evidence and does not present an unbiased opinion. There is a fairly good summary of the key points of this review at the end, the authors are extremely clear that ME/CFS is not a psychosomatic illness.
ME/CFS Research References and Abstracts
Nunes JM, Kell DB, Pretorius E.
Blood Rev. 2023 Mar 20:101075.
Abstract
ME/CFS is a debilitating chronic condition that often develops after viral or bacterial infection. Insight from the study of Long COVID/Post Acute Sequelae of COVID-19 (PASC), the post-viral syndrome associated with SARS-CoV-2 infection, might prove to be useful for understanding pathophysiological mechanisms of ME/CFS.
Disease presentation is similar between the two conditions, and a subset of Long COVID patients meet the diagnostic criteria for ME/CFS. Since Long COVID is characterized by significant vascular pathology – including endothelial dysfunction, coagulopathy, and vascular dysregulation – the question of whether or not the same biological abnormalities are of significance in ME/CFS arises.
Cardiac abnormalities have for a while now been documented in ME/CFS cohorts, with recent studies demonstrating major deficits in cerebral blood flow, and hence vascular dysregulation.
A growing body of research is demonstrating that ME/CFS is accompanied by platelet hyperactivation, anomalous clotting, a procoagulant phenotype, and endothelial dysfunction. Endothelial damage and dysregulated clotting can impair substance exchange between blood and tissues, and result in hypoperfusion, which may contribute to the manifestation of certain ME/CFS symptoms.
Here we review the ME/CFS literature to summarize cardiovascular and haematological findings documented in patients with the condition, and, in this context, briefly discuss the potential role of previously-implicated pathogens.
Overall, cardiac and haematological abnormalities are present within ME/CFS cohorts. While atherosclerotic heart disease is not significantly associated with ME/CFS, suboptimal cardiovascular function defined by reduced cardiac output, impaired cerebral blood flow, and vascular dysregulation are, and these abnormalities do not appear to be influenced by deconditioning.
Rather, these cardiac abnormalities may result from dysfunction in the (autonomic) nervous system. Plenty of recently published studies are demonstrating significant platelet hyperactivity and endothelial dysfunction in ME/CFS, as well as anomalous clotting processes. It is of particular importance to determine to what extent these cardiovascular and haematological abnormalities contribute to symptom severity, and if these two systems can be targeted for therapeutic purposes.
Viral reservoirs of herpesviruses exist in ME/CFS, and most likely contribute to cardiovascular and haematological dysfunction directly or indirectly. This review highlights the potential of studying cardiac functioning, the vasculature, and coagulation system in ME/CFS.
2. Online Health Communities in Controversy over ME/CFS and Long Covid
Sally Jackson
Journal of Health Communication, 4(2), 49–72.
Abstract
The condition known variously as myalgic encephalomyelitis, chronic fatigue syndrome, or ME/CFS has been steeped in controversy for 40 years or more. Long Covid, first noticed and named in 2020, has become entangled with the ME/CFS controversy because of striking similarities in the experiences of patients suffering from the two illnesses.
Online health communities (OHCs) have played central roles in both controversies, but these are not the kinds of roles that have been so well-documented in prior literature.
While prior research has established many ways in which participation in an OHC may benefit or otherwise affect community members themselves, this essay focuses on how OHCs contribute to positional shifts in health controversies that involve other communities as well.
Using a framework for understanding health controversies as argumentative polylogues, I show that OHCs arguing with other players have made contributions that are both effective in gaining ground for the OHCs' own goals and in elevating the overall quality of the debate. Further, in some cases these contributions have been so innovative as to suggest surprising future trajectories for OHCs.
3. LC, POTS, and ME/CFS: Lifting the Fog
Chambers, P.
Preprints 2023, 2023030418.
Abstract
These three syndromes – long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) – have many symptoms in common. The common denominator remains elusive.
The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis.
In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine.
When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT).
The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT.
Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.
Hinchado MD, Quero-Calero CD, Otero E, Gálvez I, Ortega E.
Nutrients. 2023; 15(7):1591
Abstract
Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are two medical conditions in which pain, fatigue, immune/inflammatory dysregulation, as well as various mental health disorders predominate in the diagnosis, without evidence of a clear consensus on the treatment of FM and CFS.
The main aim of this research was to analyse the possible effects of a synbiotic (Synbiotic, Gasteel Plus® (Heel España S.A.U.), through the study of pro-inflammatory/anti-inflammatory cytokines (IL-8/IL-10) and neuroendocrine biomarkers (cortisol and DHEA), in order to evaluate the interaction between inflammatory and stress responses mediated by the cytokine-HPA (hypothalamic-pituitary-adrenal) axis, as well as mental and physical health using body composition analysis, accelerometry and previously validated questionnaires.
The participants were women diagnosed with FM with or without a diagnostic of CFS. Each participant was evaluated at baseline and after the intervention, which lasted one month.
Synbiotic intervention decreased levels of perceived stress, anxiety and depression, as well as improved quality of life during daily activities.
In addition, the synbiotic generated an activation of HPA axis (physiological cortisol release) that can compensate the increased inflammatory status (elevated IL-8) observed at baseline in FM patients.
There were no detrimental changes in body composition or sleep parameters, as well as in the most of the activity/sedentarism-related parameters studied by accelerometry.
It is concluded that synbiotic nutritional supplements can improve the dysregulated immunoneuroendocrine interaction involving inflammatory and stress responses in women diagnosed with FM, particularly in those without a previous CFS diagnostic; as well as their perceived of levels stress, anxiety, depression and quality of life.
Cocchetto A, Seymour C, Mothersill C.
International Journal of Molecular Sciences. 2023; 24(7):6022.
Abstract
Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) is considered to be a multidimensional illness whose etiology is unknown. However, reports from Chernobyl, as well as those from the United States, have revealed an association between radiation exposure and the development of CFIDS. As such, we present an expanded model using a systems biology approach to explain the etiology of CFIDS as it relates to this cohort of patients.
This paper proposes an integrated model with ionizing radiation as a suggested trigger for CFIDS mediated through UVA induction and biophoton generation inside the body resulting from radiation-induced bystander effects (RIBE).
Evidence in support of this approach has been organized into a systems view linking CFIDS illness markers with the initiating events, in this case, low-dose radiation exposure. This results in the formation of reactive oxygen species (ROS) as well as important immunologic and other downstream effects.
Furthermore, the model implicates melanoma and subsequent hematopoietic dysregulation in this underlying process. Through the identification of this association with melanoma, clinical medicine, including dermatology, hematology, and oncology, can now begin to apply its expansive knowledge base to provide new treatment options for an illness that has had few effective treatments.
Maeda KI, Islam MF, Conroy KE, Jason L.
Psychol Health Med. 2023 Mar 28:1-12. [Epub ahead of print.]
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood chronic illness with many case definitions that disagree on key symptoms, including hypersensitivities to noise and lights.
The aim of the current study was to understand the prevalence rates and characteristics of these symptoms amongst people with ME/CFS and to compare them to people with another chronic illness, multiple sclerosis (MS).
International datasets consisting of 2,240 people with either ME/CFS or MS have completed the DePaul Symptom Questionnaire (DSQ) and the Short Form Health Survey Questionnaire (SF-36).
Hypersensitivities to noise and lights were indicated from items on the DSQ, and participants were analyzed against DSQ and SF-36 subscales through a multivariate analysis of covariance.
There were significantly higher percentages of people with hypersensitivities in the ME/CFS sample compared to the MS sample. Regardless of illness, participants that exhibited both hypersensitivities reported greater symptomology than those without hypersensitivities.
Healthcare providers and researchers should consider these symptoms when developing treatment plans and evaluating ME/CFS case diagnostic criteria.
Bermejo-Guerrero L, de Fuenmayor-Fernández de la Hoz CP, Guerrero-Molina MP, Martín-Jiménez P, Blázquez A, Serrano-Lorenzo P, Lora D, Morales-Conejo M, González-Martínez I, López-Jiménez EA, Martín MA, Domínguez-González C.
Journal of Clinical Medicine. 2023; 12(6):2435.
Abstract
Primary mitochondrial myopathies (PMM) are a clinically and genetically highly heterogeneous group that, in some cases, may manifest exclusively as fatigue and exercise intolerance, with minimal or no signs on examination. On these occasions, the symptoms can be confused with the much more common chronic fatigue syndrome (CFS).
Nonetheless, other possibilities must be excluded for the final diagnosis of CFS, with PMM being one of the primary differential diagnoses. For this reason, many patients with CFS undergo extensive studies, including extensive genetic testing and muscle biopsies, to rule out this possibility.
This study evaluated the diagnostic performance of growth differentiation factor-15 (GDF-15) as a potential biomarker to distinguish which patient with chronic fatigue has a mitochondrial disorder.
We studied 34 adult patients with symptoms of fatigue and exercise intolerance with a definitive diagnosis of PMM (7), CFS (22), or other non-mitochondrial disorders (5).
The results indicate that GDF-15 can accurately discriminate between patients with PMM and CFS (AUC = 0.95) and between PMM and patients with fatigue due to other non-mitochondrial disorders (AUC = 0.94). Therefore, GDF-15 emerges as a promising biomarker to select which patients with fatigue should undergo further studies to exclude mitochondrial disease.
Long-COVID Research References
Dr Katrina Pears,
Research Correspondent.
The ME Association.
