The ME Association ME/CFS (& Long Covid) Weekly Research Round-up

June 25, 2021

The weekly research round-up now includes recent publications about ME/CFS and about Long Covid. We highlight several 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 and available to anyone.

This extensive library of research is normally updated at the end of each month, but with the change in staff, it will be updated again by 01 August 2021.

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.

ME/CFS Research Published 12 June – 18 June 2021 

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

The second paper (2) looks at the similarities in ME/CFS and Long Covid. An overview of this paper by Dr Charles Shepherd, Hon. Medical Adviser to the ME Association, can be read below:

The third paper (3) looks at ME/CFS, joint hypermobility and cerebral blood flow reductions (CBF) during orthostatic stress:

“As one of proposed underlying mechanisms of orthostatic intolerance in hypermobile patients is vessel laxity, reducing the normal return of blood to the heart during orthostatic stress, we hypothesized that the CBF reduction during tilt-testing would be larger in ME/CFS patients with joint hypermobility than in patients without hypermobility.” 

The study found that hypermobile patients had significantly more postural orthostatic tachycardia syndrome (PoTS) during tilt testing than the non-hypermobile patients. It concluded that ME/CFS patients with joint hypermobility syndromes had larger CBF reductions during orthostatic stress testing than patients without hypermobility. This larger CBF reduction is independent of the heart rate and blood pressure results of the orthostatic stress test.  

ME/CFS Research References and Abstracts 

1. The circuit of symbolic violence in chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) (I): A preliminary study 

Gimeno Torrent X Health Care Women International. 2021 Jun 14:1-36 


Objective:How can it be that a disease as serious as CFS affecting such a large number of people could be so unknown to the general population? The answer given to this question is based on Pierre Bourdieu's analyzes of symbolic violence. 

Method:The “letters to the editor” by CFS patients to three national Spanish newspapers were subjected to various qualitative and quantitative analyzes. 

Results:Based on the qualitative analyzes and their theoretical interpretation, 13 mechanisms of symbolic violence were identified: non-recognition, institutionalized un-care, condescension, authorized imposition of illegitimate verdicts, delegitimization, disintegration, imposition of discourse, euphemization, silencing, invisibilization, isolation, uncommunication, and self-blaming.

Multiple Correspondence Analysis made it possible to identify that the structural mechanisms (non-recognition, disintegration) were combined with the most symbolic ones, which came to the forefront producing the observed effects of symbolic violence. The 13 clusters obtained in the Agglomerative Hierarchical Clustering confirmed this result.  

2. Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis? 

Bornstein SR, Voit-Bak K, Donate T, Rodionov RN, Gainetdinov RR, Tselmin S, Kanczkowski W, Müller GM, Achleitner M, Wang J, Licinio J, Bauer M, Young AH, Thuret S, Bechmann N, Straube R. Molecular Psychiatry. 2021 Jun 17. Epub ahead of print. 


As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called “post-COVID syndrome” or “long-COVID” [1].

There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups.

Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.  

3. The Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Joint Hypermobility Show Larger Cerebral Blood Flow Reductions during Orthostatic Stress Testing Than Patients without Hypermobility: A Case Control Study 

Van Campen, LMC, Rowe PC, Visser FC Medical Research Archives, [S.l.], v. 9, n. 6, june 2021. 


Aims:An abnormal reduction in cerebral blood flow (CBF) during orthostatic stress is common in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition with more prevalent joint hypermobility than in the healthy population. As one of proposed underlying mechanisms of orthostatic intolerance in hypermobile patients is vessel laxity, reducing the normal return of blood to the heart during orthostatic stress, we hypothesized that the CBF reduction during tilt-testing would be larger in ME/CFS patients with joint hypermobility than in patients without hypermobility. 

Methods:In this case-control study, 100 female ME/CFS cases with joint hypermobility, who had undergone tilt-testing with CBF measurements, were compared to 100 female ME/CFS patients without joint hypermobility, matched by age and disease duration. 

Results: No differences in baseline characteristics were found between groups. The hypermobile patients had significantly more postural orthostatic tachycardia syndrome (POTS) during tilt testing than the non-hypermobile ones. Compared to supine CBF, the degree of CBF reduction during the tilt was significantly larger in hypermobile cases than in the non-hypermobile controls: -32 (6)% vs -23 (7)% (p<0.0001) The larger CBF reduction in hypermobile patients was not only present in POTS patients: -33 (6)% vs -24 (4)%, but also in patients with a normal heart rate and blood pressure response to tilt testing: -31 (6)% vs -22 (9)%: (both p<0.0001). 

Conclusions:ME/CFS patients with joint hypermobility syndromes have larger CBF reductions during orthostatic stress testing than patients without hypermobility. This larger CBF reduction is independent of the heart rate and blood pressure results of the orthostatic stress test. 

4. Performance Validity and Outcome of Cognitive Behavior Therapy in Patients with Chronic Fatigue Syndrome 

Roor, J., Dandachi-FitzGerald, B., Peters, M., Knoop, H., & Ponds, R.  Journal of the International Neuropsychological Society, 1-10. 2021 


Objective:There is limited research examining the impact of the validity of cognitive test performance on treatment outcome. All known studies to date have operationalized performance validity dichotomously, leading to the loss of predictive information. Using the range of scores on a performance validity test (PVT), we hypothesized that lower performance at baseline was related to a worse treatment outcome following cognitive behavioral therapy (CBT) in patients with Chronic Fatigue Syndrome (CFS) and to lower adherence to treatment. 

Method:Archival data of 1081 outpatients treated with CBT for CFS were used in this study. At baseline, all patients were assessed with a PVT, the Amsterdam Short-Term Memory test (ASTM). Questionnaires assessing fatigue, physical disabilities, psychological distress, and level of functional impairment were administered before and after CBT. 

Results:Our main hypothesis was not confirmed: the total ASTM score was not significantly associated with outcomes at follow-up. However, patients with a missing follow-up assessment had a lower ASTM performance at baseline, reported higher levels of physical limitations, and completed fewer therapy sessions. 

Conclusions:CFS p atients who scored low on the ASTM during baseline assessment are more likely to complete fewer therapy sessions and not to complete follow-up assessment, indicative of limited adherence to treatment. However, if these patients were retained in the intervention, their response to CBT for CFS was comparable with subjects who score high on the ASTM. This finding calls for more research to better understand the impact of performance validity on engagement with treatment and outcomes. 

5. Intersections between pneumonia, lowered oxygen saturation percentage and immune activation mediate depression, anxiety and chronic fatigue syndrome-like symptoms due to COVID-19: a nomothetic network approach 

Hawraa Kadhem Al-Jassas, Hussein Kadhem Al-Hakeim, Michael Maes medRxiv 2021.06.12.21258815 


Background: COVID-19 is associated with neuropsychiatric symptoms including increased depressive, anxiety and chronic fatigue-syndrome (CFS)-like physiosomatic (previously known as psychosomatic) symptoms.

Aims: To delineate the associations between affective and CFS-like symptoms in COVID-19 and chest CT-scan anomalies (CCTAs), oxygen saturation (SpO2), interleukin (IL)-6, IL-10, C-Reactive Protein (CRP), albumin, calcium, magnesium, soluble angiotensin converting enzyme (ACE2) and soluble advanced glycation products (sRAGEs).  

Method: The above biomarkers were assessed in 60 COVID-19 patients and 30 heathy controls who had measurements of the Hamilton Depression (HDRS) and Anxiety (HAM-A) and the Fibromyalgia and Chronic Fatigue (FF) Rating Scales.  

Results: Partial Least Squares-SEM analysis showed that reliable latent vectors could be extracted from a) key depressive and anxiety and physiosomatic symptoms (the physio-affective or PA-core), b) IL-6, IL-10, CRP, albumin, calcium, and sRAGEs (the immune response core); and c) different CCTAs (including ground glass opacities, consolidation, and crazy paving) and lowered SpO2% (lung lesions). PLS showed that 70.0% of the variance in the PA-core was explained by the regression on the immune response and lung lesions latent vectors.

Moreover, one common “infection-immune-inflammatory (III) core” underpins pneumonia-associated CCTAs, lowered SpO2 and immune activation, and this III core explains 70% of the variance in the PA core, and a relevant part of the variance in melancholia, insomnia, and neurocognitive symptoms.  

Discussion:Acute SARS-CoV-2 infection is accompanied by lung lesions and lowered SpO2 which both may cause activated immune-inflammatory pathways, which mediate the effects of the former on the PA-core and other neuropsychiatric symptoms due to SARS-CoV-2 infection. 

6. Epistemic in/justice in patient participation. A discourse analysis of the Dutch ME/CFS Health Council advisory process 

de Boer ML. Sociology of Health & Illness. 2021 Jun 17. Epub ahead of print. 


In healthcare settings, patient participation is increasingly adopted as a possible remedy to ill people suffering from ‘epistemic injustices' – that is to their unfair harming as knowers.

In exploring and interpreting patient participation discourses within the 2013-2018 Dutch Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) Health Council advisory process, this paper assesses the epistemological emancipatory value of this participatory practice.

It reveals that in the analysed case, patient representatives predominantly offer biomedical knowledge about ME/CFS. They frame this condition as primarily somatic, and accordingly, perceive appropriate diagnostic criteria, research avenues and treatment options as quantifiable, objectifiable and explicitly non-psychogenic.

This paper argues that such a dominant biomedical patient participatory practice is ambiguous in terms of its ability to correct epistemic injustices towards ill people. Biomedicalized patient participation may enhance people's credibility and their ability to make sense of their illness, but it may also undermine their valid position within participatory practices as well as lead to (sustaining) biased and reductive ideas about who ill people are and what kind of knowledge they hold.

The final section of this paper offers a brief reflection on how to navigate such biomedicalized participatory practices in order to attain more emancipatory ones. 

Long-COVID Research References  

  1. Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex 
  2. Causation or confounding: why controls are critical for characterizing long COVID 
  3. The Conundrum of ‘Long-COVID-19ʹ: A Narrative Review 
  4. Long-Term Predictions of COVID-19 in Some Countries by the SIRD Model 
  5. Long COVID has exposed medicine's blind-spot 
  6. Autonomic dysfunction following COVID-19 infection: an early experience 
  7. From early limbic inflammation to long COVID sequelae 
  8. Causation or confounding: why controls are critical for characterizing long COVID 
  9. Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation 
  10. Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex 
  11. The presence of headache at onset in SARS-CoV-2 infection is associated with long-term post-COVID headache and fatigue: A case-control study 

Katrina Pears, Research Correspondent, ME Association

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