The ME Association End of Week Research Round-up and Index Update

July 6, 2020

Charlotte Stephens, Research Correspondent, ME Association.

We show below brief summaries of the research studies about ME/CFS that have been published in the last week, followed by the abstracts from those studies.

All research relating to ME/CFS can be located in the Index of ME/CFS Published Research which is correct to the end of June 2020 and can be downloaded for free.

It is an A-Z of the most important published research studies and selected key documents and articles, listed by subject matter, on myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS).

You can use it to easily locate and read any research in a particular area that you might be interested in, 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 from the ME Association that provide lay explanations of the more important and interesting work that has been published to date.

ME/CFS Research Published 26 June – 02 July 2020

This week, 10 new research studies have been published, highlights include:

  • Recommendations on how Occupational Therapists can assist University students affected by ME/CFS with their studies and improve their quality of life.
  • A study by researchers from America on whether Cardiopulmonary exercise testing (CPET) can be used as a reliable biomarker for ME/CFS. They concluded “CPET measurements demonstrate adequate responsiveness and reproducibility for research and clinical applications.”
  • Researchers from Japan studied autoantibodies against adrenergic receptors in the brains of patients with ME/CFS and found some potential biomarkers for ME/CFS.
  • Researchers from DePaul’s university in America carried out a literature review on short- and long-term health consequences of prior epidemics and infections to assess potential health complications that may be associated with post-COVID-19 recovery.
    They found that Past research on post-epidemic and post-infection recovery has suggested that such complications include the development of severe fatigue.
  • An article from America summarising the range of methods used in successful US disability claims, which include documentation of the functional impact of post-exertional malaise and the use of methods that provide objective evidence of impairment.

ME/CFS Research References and Abstracts

1. Chu L et al. (2020)
Environmental accommodations for university students affected by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Work [Epub ahead of Print].

Background: Today, 24% of college and university students are affected by a chronic health condition or disability. Existing support programs, including disability services, within colleges and universities are often unaccustomed to addressing the fluctuating and unpredictable changes in health and functioning faced by students with severe chronic illnesses.

This situation is especially difficult for students with lesser-known, invisible diseases like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a complex disease affecting up to 2.5 million Americans which often begins in late adolescence or young adulthood.

Objective: Educate occupational therapists (OTs) about ME/CFS and steps they can take to assist students

Methods: This work is based on a review of the scientific literature and our collective professional/ personal experiences.

Results: ME/CFS’ effects on multiple organ systems combined with the unusual symptom of post-exertional malaise frequently and substantially decrease function. Currently, no effective disease-modifying treatments have been established.

Nevertheless, OTs can help students maximize their participation in university life by identifying potential obstacles, formulating practical solutions and negotiating with their institutions to implement reasonable, environmental accommodations.

Conclusions: Through understanding this disease, being aware of possible support options, and recommending them as appropriate, OTs are in unique position to greatly improve these students’ lives.

2. Davenport T et al. (2020)
Properties of measurements obtained during cardiopulmonary exercise testing in individuals with myalgic encephalomyelitis/chronic fatigue syndrome.
Work [Epub ahead of print].

Background: Diminished cardiopulmonary exercise test (CPET) performance indicates the physiological basis for reduced capacity for activities of daily living and work. Thus, it may be a biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Objective: To determine statistical properties of cardiac, pulmonary, and metabolic measurements obtained during CPET in people with ME/CFS.

Methods: Fifty-one females with ME/CFS and 10 sedentary females with similar age and body mass received cardiac, pulmonary, and metabolic measurements during 2 CPETs separated by 24 hours.

Two-way analysis of variance and effect size calculations (Cohen’s d) were used to assess the magnitude and statistical significance of differences in measurements between groups. Reliability of CPET measurements was estimated using intraclass correlation coefficients (formula 2,1; ICC2,1).

Responsiveness of CPET measurements was assessed using minimum detectable change outside the 95% confidence interval (MDC95) and coefficients of variation (CoV).

Results: CPET measurements demonstrated moderate to high reliability for individuals with ME/CFS. Comparing subjects with ME/CFS and control subjects yielded moderate to large effect sizes on all CPET measurements. MDC95 for all individuals with ME/CFS generally exceeded control subjects and CoVs for CPET measurements were comparable between groups.

Conclusions: CPET measurements demonstrate adequate responsiveness and reproducibility for research and clinical applications.

3. Fujii H et al. (2020)
Altered Structural Brain Networks Related to Adrenergic/Muscarinic Receptor Autoantibodies in Chronic Fatigue Syndrome.
Journal of Neuroimaging [Epub ahead of print].

Background and purpose: Recent studies suggest that the autoantibodies against adrenergic/muscarinic receptors might be one of the causes and potential markers of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

The purpose of this study was to investigate the structural network changes related to autoantibody titers against adrenergic/muscarinic receptors in ME/CFS by performing a single-subject gray matter similarity-based structural network analysis.

Methods: We prospectively examined 89 consecutive right-handed ME/CFS patients who underwent both brain MRI including 3D T1-wighted images and a blood analysis of autoantibodies titers against β1 adrenergic receptor (β1 AdR-Ab), β2 AdR-Ab, M3 acetylcholine receptor (M3 AchR-Ab), and M4 AchR-Ab.

Single-subject gray matter similarity-based structural networks were extracted from segmented gray matter images for each patient. We calculated local network properties (betweenness centrality, clustering coefficient, and characteristic path length) and global network properties (normalized path length λ, normalized clustering coefficient γ, and small-world network value δ). We investigated the correlations between the autoantibody titers and regional gray matter/white matter volumes, the local network properties, and the global network properties.

Results: Betweenness centrality showed a significant positive correlation with β1-AdR-Ab in the right dorsolateral prefrontal cortex. The characteristic path length showed a significant negative correlation with β2-AdR-Ab in the right precentral gyrus. There were no significant correlations between the antibody titers and the regional gray matter/white matter volumes, and the global network properties.

Conclusions: Our findings suggest that β1 AdR-Ab and β2 AdR-Ab are potential markers of ME/CFS.

4. Islam M et al. (2020)
Post-viral fatigue and COVID-19: lessons from past epidemics.
Fatigue: Biomedicine, Health and Behaviour [Epub ahead of print].

The COVID-19 pandemic, resulting from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has severely impacted the population worldwide with a great mortality rate.

The current article reviews the literature on short- and long-term health consequences of prior epidemics and infections to assess potential health complications that may be associated with post-COVID-19 recovery.

Past research on post-epidemic and post-infection recovery has suggested that such complications include the development of severe fatigue. Certain factors, such as the severity of infection, in addition to the ‘cytokine storm’ experienced by many COVID-19 patients, may contribute to the development of later health problems.

We suggest that the patterns observed in past epidemics and infections may re-occur in the current COVID-19 pandemic.

5. Lee J et al. (2020)
Clinically accessible tools for documenting the impact of orthostatic intolerance on symptoms and function in ME/CFS.
Work [Epuab ahead of print].

Background: Clinical observations have indicated that hours of upright activity (HUA) reported by Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients correlated with orthostatic symptoms and impaired physical function. This study examined the relationship between HUA and orthostatic intolerance (OI).

Methods: Twenty-five female ME/CFS subjects and 25 age and race matched female healthy controls (HCs) were enrolled. Subjects reported HUA (defined as hours per day spent with feet on the floor) and completed questionnaires to assess the impact of OI on daily activities and symptoms. ME/CFS patients were categorized into those with <5 HUA and ≥5 HUA and analyzed by employment status. Data analysis used one-way ANOVA.

Results: ME/CFS patients had fewer HUA, worse symptoms and greater interference with daily activities due to OI than HCs. The <5 HUA ME/CFS subjects had more severe OI related symptoms than ≥5 HUA ME/CFS subjects even though OI interfered with daily activities similarly. Only 33% of ME/CFS subjects were employed and all were ≥5 HUA ME/CFS subjects with an average HUA of 8.

Conclusions: ME/CFS subjects experienced more frequent and severe OI symptoms, higher interference with daily activities, and reduced ability to work than HCs. Reported HUA and assessment of OI using standardized instruments may be useful clinical tools for physicians in the diagnosis, treatment and management of ME/CFS patients.

6. Mateo L et al. (2020)
Post-exertional symptoms distinguish myalgic encephalomyelitis/chronic fatigue syndrome subjects from healthy controls.
Work [Epub ahead of print].

Background: Post-exertional malaise (PEM) is an exacerbation of symptoms that leads to a reduction in functionality. Recognition of PEM is important for the diagnosis and treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Objective: Symptoms following cardiopulmonary exercise testing were compared between ME/CFS patients and healthy controls.

Methods: Open-ended questionnaires were provided to subjects following two maximal exercise tests, 24 hours apart. Subjects evaluated how they felt at five time points. Responses were classified into 19 symptom categories.

Results: ME/CFS subjects (n = 49) reported an average of 14±7 symptoms compared to 4±3 by controls (n = 10). During the seven days afterwards, ME/CFS subjects reported 4±3 symptoms. None were reported by controls.

Fatigue, cognitive dysfunction, and sleep problems were reported with the greatest frequency. ME/CFS patients reported more symptom categories at higher frequencies than controls. The largest differences were observed in cognitive dysfunction, decrease in function, and positive feelings.

Conclusions: A standardized exertional stimulus produced prolonged, diverse symptoms in ME/CFS subjects. This provides clues to the underlying pathophysiology of ME/CFS, leading to improved diagnosis and treatment.

7. Podell R et al. (2020)
Documenting disability in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Work [Epub ahead of print].

Background: According to the 2015 National Academy of Medicine report, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) “is a serious, chronic, complex, and systemic disease that frequently and dramatically limits the activities of affected patients.”

ME/CFS affects between 1 and 2.5 million Americans, leaving as many as 75% unable to work due to physical, cognitive and functional impairment.

Unfortunately, many doctors and lawyers lack the knowledge of how to properly document an ME/CFS disability claim, leaving patients unable to access disability benefits.

Objective: The goal of this article is to summarize the approaches used by experienced clinicians and lawyers in successful ME/CFS disability claims.

Methods: The authors reviewed the types of US disability insurance programs and the evidence commonly required by these programs to demonstrate ME/CFS disability.

Results: This article summarizes the range of methods used in successful US disability claims, which include documentation of the functional impact of post-exertional malaise and the use of methods that provide objective evidence of impairment.

Conclusions: Medical providers and lawyers can use these tested methods to obtaining disability benefits for people with ME/CFS. Physical therapists, occupational therapists, and other specialists play an important role in providing objective evidence for ME/CFS disability claims.

8. Priou S et al. (2020)
Clinical History Segment Extraction From Chronic Fatigue Syndrome Assessments to Model Disease Trajectories.
Studies in Health Technology and Information 270: 98-102.

Chronic fatigue syndrome (CFS) is a long-term illness with a wide range of symptoms and condition trajectories. To improve the understanding of these, automated analysis of large amounts of patient data holds promise. Routinely documented assessments are useful for large-scale analysis, however relevant information is mainly in free text.

As a first step to extract symptom and condition trajectories, natural language processing (NLP) methods are useful to identify important textual content and relevant information. In this paper, we propose an agnostic NLP method of extracting segments of patients' clinical histories in CFS assessments. Moreover, we present initial results on the advantage of using these segments to quantify and analyse the presence of certain clinically relevant concepts.

9. Tokunaga K et al. (2020)
Inclusion of family members without ME/CFS in research studies promotes discovery of biomarkers specific for ME/CFS.
Work [Epuab ahead of print].


Background: The search for a biomarker specific for ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) has been long, arduous and, to date, unsuccessful. Researchers need to consider their expenditures on each new candidate biomarker.

In a previous study of antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer lymphocytes, we found lower ADCC for ME/CFS patients vs. unrelated donors but ruled against low ADCC as a biomarker because of similar ADCC for patients vs. their family members without ME/CFS.

Objective: We applied inclusion of family members without ME/CFS, from families with multiple CFS patients, as a second non-ME/CFS control group in order to re-examine inflammation in ME/CFS.

Method: Total and CD16A-positive ‘non-classical’ anti-inflammatory monocytes were monitored.

Results: Non-classical monocytes were elevated for patients vs. unrelated healthy donors but these differences were insignificant between patients vs. unaffected family members.

Conclusions: Inclusion of family members ruled against biomarker considerations for the monocytes characterized. These pilot findings for the non-classical monocytes are novel in the field of ME/CFS.

We recommend that occupational therapists advocate and explain to family members without ME/CFS the need for the family members’ participation as a second set of controls in pilot studies to rapidly eliminate false biomarkers, optimize patient participation, and save researchers’ labor.

10. Vink M and Vink-Niese A (2020)
Graded exercise therapy doesn’t restore the ability to work in ME/CFS. Rethinking of a Cochrane review.
Work [Epub ahead of print].

Background: Cochrane recently amended its exercise review for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in response to an official complaint.

Objective: To determine if the amended review has addressed the concerns raised about the previous review and if exercise is an effective treatment that restores the ability to work in ME/CFS.

Method: The authors reviewed the amended Cochrane exercise review and the eight trials in it by paying particular interest to the objective outcomes. We also summarised the recently published review of work rehabilitation and medical retirement for ME/CFS.

Results: The Cochrane review concluded that graded exercise therapy (GET) improves fatigue at the end of treatment compared to no-treatment. However, the review did not consider the unreliability of subjective outcomes in non-blinded trials, the objective outcomes which showed that GET is not effective, or the serious flaws of the studies included in the review.

These flaws included badly matched control groups, relying on an unreliable fatigue instrument as primary outcome, outcome switching, p-hacking, ignoring evidence of harms, etc. The review did also not take into account that GET does not restore the ability to work.

Conclusion: GET not only fails to objectively improve function significantly or to restore the ability to work, but it’s also detrimental to the health of≥50% of patients, according to a multitude of patient surveys. Consequently, it should not be recommended.

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