Research round up

ME/CFS Research Published 31 July to 6 August 2021

August 17, 2021

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).

All research relating to ME/CFS can be located in the ME Association: Index of ME/CFS Published Research. It is a FREE resource, available to anyone, and updated at the beginning of each month.

The Index provides an A-Z of published research studies, selected key documents and articles, listed by subject matter, on myalgic encephalomyelitis, myalgic encephalopathy, and/or chronic fatigue syndrome (ME/CFS).

You can use it to easily locate and read any research that you might be interested in regard to, e.g., epidemiology, infection, neurology, post-exertional malaise etc.

You can also find the Research Index in the Research section of the website together with a list of Research Summaries that provide more detailed lay explanations of the more interesting work that has been published to date.

Seven new research studies on ME/CFS have been published during this period and we have also included nine studies on Long Covid. We highlight two on ME/CFS from the selection below:   

The first study (1) examined how Long Covid resembles ME/CFS and explores current understanding to establish what contributes to symptoms. The results found:   

QUOTE: “ME/CFS-like features were found in 27% of our sample. ME/CFS-like group showed worse sleep quality, fatigue, pain, depressive symptoms, subjective cognitive complaints”  

This study further raises the concerns of a ME/CFS-like pandemic following Covid-19 infection.   

The sixth study (6) examined the role of the central nervous system (CNS) in the pathophysiology of ME/CFS. It investigates the microstructural changes in the brain using diffusion tensor imaging (DTI) (an MRI technique) to determine if there are abnormalities in ME/CFS.  

The study found microstructural changes in ME/CFS, and significant changes in key areas of the brain compared to healthy controls. Results could potentially act as a future biomarker.  

ME/CFS Research References and Abstracts  

1. Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors?  

Mantovani E, Mariotto S, Gabbiani D, Dorelli G, Bozzetti S, Federico A, Zanzoni S, Girelli D, Crisafulli E, Ferrari S, Tamburin S. J Neurovirol. 2021 Aug 2:1–7. Epub ahead of print.   


SARS-CoV-2 survivors may report persistent symptoms that resemble myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).  

We explored (a) ME/CFS-like symptom prevalence and (b) whether axonal, inflammatory, and/or lung changes may contribute to ME/CFS-like symptoms in SARS-CoV-2 survivors through clinical, neuropsychiatric, neuropsychological, lung function assessment, and serum neurofilament light chain, an axonal damage biomarker.  

ME/CFS-like features were found in 27% of our sample. ME/CFS-like group showed worse sleep quality, fatigue, pain, depressive symptoms, subjective cognitive complaints, Borg baseline dyspnea of the 6-min walking test vs. those without ME/CFS-like symptoms. These preliminary findings raise concern on a possible future ME/CFS-like pandemic in SARS-CoV-2 survivors.   

2. Questioning Biomedicine's Privileging of Disease and Measurability  

Kroll C. AMA J Ethics. 2021 Jul 1;23(7):E537-541.   


Within biomedicine, the diagnosis of disease is often privileged over a patient's experience of illness. Yet up to 30% of primary care visits might be attributable to persistent illness without a diagnosed disease, including functional somatic syndromes like fibromyalgia and chronic fatigue syndrome.  

When clinicians are unable to diagnose disease or correlate symptoms with measurable changes in biomarkers, patients experiencing such an illness are at increased risk for suspicion, misplaced questioning, or having their motives misinterpreted through damaging social and cultural narratives about gender, race, ethnicity, socioeconomic status, or disability.  

Adhering strictly to a biomedical model of thinking about disease and diagnosis can prevent clinicians from empathically engaging with patients and helping them navigate their illness experiences.   

3. ME/CFS: Past, Present and Future  

Weir W & Speight N. Healthcare2021, 9(8), 984  


This review raises a number of compelling issues related to the condition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).  

Some historical perspective is necessary in order to highlight the nature of the controversy concerning its causation. Throughout history, a pattern tends to repeat itself when natural phenomena require explanation.  

Dogma usually arrives first, then it is eventually replaced by scientific understanding. The same pattern is unfolding in relation to ME/CFS, but supporters of the psychological dogma surrounding its causation remain stubbornly resistant, even in the face of compelling scientific evidence to the contrary.  

Acceptance of the latter is not just an academic issue; the route to proper understanding and treatment of ME/CFS is through further scientific research rather than psychological theorisation. Only then will a long-suffering patient group benefit.  

4. Broken Connections: The Evidence for Neuroglial Failure in ME/CFS  

Renz-Polster H and Binenzle D. OSF Preprints.  


In spite of decades of research, the pathobiology of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is still poorly understood.  

Several pathomechanisms have been identified, yet it remains unclear how they are related and which of them may be upstream or downstream. 

In this paper, we present a theoretical strategy that may help clarify the causal chain of pathophysiological events in ME/CFS. We propose to focus on the common final histological pathway of ME/CFS and suggest to ask: Which cellular compartment may explain the pathological processes and clinical manifestations observed in ME/CFS?  

Any functional unit consistently identified through this search may then be a plausible candidate for further exploration. For this “histological” approach we have compiled a list of 22 undisputed clinical and pathophysiological features of ME/CFS that need to be plausibly and most directly explained by the dysfunctional cellular unit in question.  

For each feature we have searched the literature for pathophysiological explanations and analyzed if they may point to the same functional cellular unit. Through this search we have identified the CNS neuroglia – microglia and astroglia – as the one functional unit in the human body which may best explain all and any of the clinical and pathological features, dysfunctions and observations described for ME/CFS.  

While this points to neuroinflammation as the central hub in ME/CFS, it also points to a novel understanding of the neuroimmune basis of ME/CFS.  

After all, the neuroglial cells are now understood as the functional matrix of the human brain connectome which operates beyond and above specific brain centers, receptor units or neurotransmitter systems and integrates innate immune functions with CNS regulatory functions pertaining to autonomous regulation, cellular metabolism and the stress response.  

5. Diffusion tensor imaging reveals neuronal microstructural changes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome  

Thapaliya K, Marshall-Gradisnik S, Staines D, Barnden L. Eur J Neurosci. 2021 Aug 6. [Epub ahead of print.]   


Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) patients suffer from a variety of physical and neurological complaints indicating the central nervous system plays a role in ME/CFS pathophysiology.  

Diffusion tensor imaging (DTI) has been used to study microstructural changes in neurodegenerative diseases. In this study, we evaluated DTI parameters to investigate microstructural abnormalities in ME/CFS patients.  

We estimated DTI parameters in 25 ME/CFS patients who met Fukuda criteria (ME/CFSFukuda ), 18 ME/CFS patients who met International Consent Criteria (ICC) (ME/CFSICC ) only, and 26 healthy control subjects (HC).  

In addition to voxel-based DTI-parameter group comparisons, we performed voxel-based DTI-parameter interaction-with-group regressions with clinical and autonomic measures to test for abnormal regressions.  

Group comparisons between ME/CFSICC and HC detected significant clusters (a) with decreased axial diffusivity (p=0.001) and mean diffusivity (p=0.01) in the descending cortico-cerebellar tract in the midbrain and pons, and (b) with increased transverse diffusivity in the medulla.  

The mode of anisotropy was significantly decreased (p=0.001) in a cluster in the superior longitudinal fasciculus region. Voxel-based group comparisons between ME/CFSFukuda and HC did not detect significant clusters. For ME/CFSICC and HC, DTI parameter interaction-with-group regressions were abnormal for the clinical measures of information processing score, SF36 physical, sleep disturbance score, and respiration rate in both grey and white matter regions.  

Our study demonstrated that DTI parameters are sensitive to microstructural changes in ME/CFSICC and could potentially act as an imaging biomarker of abnormal pathophysiology in ME/CFS. The study also shows that strict case definitions are essential in investigation of the pathophysiology of ME/CFS.  

6. Patients with Persistent Polyclonal B-Cell Lymphocytosis Share the Symptomatic Criteria of Systemic Exertion Intolerance Disease  

Morizot R, de Korwin JD, Feugier P, Broséus J, Troussard X, Lesesve JF. J Clin Med. 2021 Jul 29;10(15):3374.  


Introduction:Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare and still poorly understood entity, with 90% of cases occurring in female smokers.  

Patients often appear tired and in pain, but the clinical symptoms remain imprecise. The main risk is the development of lymphoma in some cases.  

To better understand the characteristics of the fatigue associated with PPBL and study its relationship with systemic exertion intolerance disease (SEID), we analyzed the symptoms in a cohort of patients with PPBL included in the French national registry.   

Material and methods: An anonymous questionnaire following the recommendations of the Institute of Medicine/National Academy of Medicine for screening of the new SEID criteria was created in French and mailed to 50 patients.  

Results:Thirty-nine (78%) contacted patients responded. The studied population was mainly constituted of women (90%) with an average age of 50 (18-59) years. Smoking was a constant factor in all patients.  

A total of 28/39 (72%) respondents met the SEID symptoms criteria. Severe chronic fatigue for more than 6 months was noted in 36/39 cases (92%). Unrefreshing sleep, post-exertional malaise, cognitive impairment, and orthostatic intolerance were described in 30/39 (77%), 32/39 (82%), 28/39 (72%), and 27/39 (69%) cases, respectively. Pain (arthralgia, myalgia, headache) was present in 26/39 (67%) cases.  

The most prominent SEID symptoms were fatigue, followed by post-exercise discomfort and cognitive difficulties. The most disabling symptom was non-restorative sleep, followed by pain. An inflammatory and/or autoimmune context was noted in 13 patients (33%), and these comorbidities could have favored the deterioration of the general condition. Three patients also presented with fibromyalgia. However, 3 patients did not mention any complaints.  

Conclusion:This survey indicated that patients with PPBL most often initially presented with disabling chronic fatigue, chronic pain, and other symptoms suggestive of SEID but requiring more studies to confirm it. Education of medical staff about the symptoms of PPBL should be encouraged to better assess this peculiar condition.  

7. Successful Psychological Strategies of Experienced Chronic Fatigue Patients: A Qualitative Study  

Hall KH, Amos C, Jaye C, Young J. Journal of Patient Experience.   


Trying to care for patients with medically unexplained symptoms (MUS) can lead to frustration and disappointment for both patients and health care professionals alike.  

Learning positive ways to assist patients avoids professionals collapsing into therapeutic nihilism. We sought to understand how people with such symptoms can live well despite (or even because of) their condition. Chronic fatigue was chosen as the exemplar symptom. Participants were invited to join the research if they, themselves, considered they were living well with this symptom.  

One-on-one interviews using an appreciative enquiry approach were performed and thematic analysis undertaken. Twelve participants were interviewed before data saturation occurred. The emotional stance or relationship a participant had with, and towards, their illness was the primary determinant underlying their interpretation of “living well.”  

Five major themes of this meta-theme were identified: (1) engaging with elusiveness, (2) befriending uncertainty, (3) reflecting on self, (4) living creatively, and (5) moving in stillness. Encouraging patients who are struggling with MUS to consider how they emotionally engage with their illness via these 5 positive dynamics may lead to better health outcomes for patients and happier, more fulfilled health care professionals.   

Long-COVID Research References   

  1. The Importance of Listening in Treating Invisible Illness and Long-Haul COVID-19  
  1. Prevalence and Predictors of Persistence of COVID-19 Symptoms in Older Adults: A Single-Center Study  
  1. Multi-Disciplinary Collaborative Consensus Guidance Statement on the Assessment and Treatment of Fatigue in Post-Acute Sequelae of SARS-CoV-2 infection (PASC) Patients  
  1. Descriptive analysis of long COVID sequelae identified in a multidisciplinary clinic serving hospitalised and non-hospitalised patients  
  1. Recommendations for the recognition, diagnosis, and management of long covid: A Delphi study  
  1. Setting Priorities to Address Research Gaps in Long-term COVID-19 Outcomes in Children  
  1. Long-term SARS-CoV-2-specific immune and inflammatory responses in individuals recovering from COVID-19 with and without post-acute symptoms  
  1. Exertional intolerance and dyspnea with preserved lung function: an emerging long COVID phenotype?  
  1. Long COVID: What is Known and What We Still Need to Know  

Katrina Pears, Research Correspondent, ME Association. 




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