Research Roundup: ME/CFS Research Published 13-19 November 2021

November 25, 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).


The ME Association maintains a comprehensive index of published research on ME/CFS and Long Covid that is free to use and updated weekly.

ME/CFS Research Published 13 – 19 November 2021  

There have been four new research studies on ME/CFS but nine studies on Long Covid this week.  

None of these studies particularly caught our attention this week as they did not conduct biological studies, i.e. they are reviews or social studies. We have highlighted two papers on ME/CFS from the selection below: 

Paper one (1) will certainly cause a disheartening response from many of you in our ME/CFS community as this paper looks at treatment options and does not take into account the new published NICE guidelines. We will not go into the details of this paper any further, and it is perplexing how this paper passed through the peer-review process.  

Paper three (3) is a review paper on a working hypothesis (a supposition which is a good starting point for further investigation) on Epstein-Barr virus (EBV) and ME/CFS. The authors propose that the cause of EBV originates from poor observation of the T cells (type of white blood cell) which means that cells become infected. 

Further to this the authors propose that invasion of pathogens like EBV could be a risk factor for developing ME/CFS, especially in a subset of patients who are more susceptible to EBV due to specific genes. The authors also hope that anti-EBV therapies such as T cell immunotherapy could help a selection of ME/CFS patients, these options are discussed in the paper. 

This paper does not tell us anything new, there is no new evidence for the link between EBV infection and ME/CFS, this still needs to be confirmed. The paper finishes with possible avenues which could be investigated next, such as decreased T cell activation, biomarkers and efficiency of anti-EBV therapies. 

ME/CFS Research References and Abstracts  

1. Evidence-Based Care for People with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis 

Sharpe M, Chalder T, White PD.  
J Gen Intern Med. 2021 Nov 17. [Epub ahead of print.]  


Chronic fatigue syndrome (CFS), sometimes referred to as myalgic encephalomyelitis (ME) and often as CFS/ME, is an illness characterized by disabling fatigue and other symptoms, typically worsened by activity.  

The main evidence-based treatments are rehabilitative in nature and include specific types of cognitive behavior therapy (CBT) and graded exercise therapy (GET).  

In this article, we briefly review the evidence for their safety and effectiveness and propose that much of the controversy about them arises from misunderstandings about their nature and delivery. 

In particular, we emphasize that successful rehabilitation from CFS/ME does not indicate that the illness is not real.  

We recommend that rehabilitative treatment always be preceded by a thorough clinical assessment and delivered by appropriately trained therapists working in close collaboration with the patient.  

We conclude that properly applied rehabilitative treatments offer the best hope of safely improving fatigue and function for patients with CFS/ME. However, we also recognize the need for more research into the treatment of this neglected condition, especially for those most severely disabled by it. 

2. Factors related to educational adaptations and social life at school experienced by young people with CFS/ME: a qualitative study 

Similä WA, Nøst TH, Helland IB, Rø TB.  
BMJ Open. 2021 Nov 18;11(11):e051094. 


Objectives: To explore factors perceived as positive or negative among young people with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in relation to school and everyday life. 

Design: A qualitative study with semistructured individual interviews performed at the local hospital or at the informants' homes between September 2017 and January 2018, with an additional telephone interview to collect data on experiences from the COVID-19 pandemic, conducted in September 2020. Data were analysed using a grounded theory approach. 

Setting: The informants were recruited from two university hospitals that offer interdisciplinary assessments of young people with CFS/ME from various parts of Norway. 

Participants: Five males and 13 females aged 13-21 years with CFS/ME diagnosed 3-56 months prior to the interviews participated. 

Results: The informants were concerned about a lack of educational adaptations and missed social life at school. Educational and social adaptations could improve schooling and health among young people with CFS/ME. Negative experiences were related to a lack of knowledge about CFS/ME among school personnel and young people's difficulties to limit activities. Online teaching as experienced during the COVID-19 pandemic was described as positive both for education and social life. 

Conclusions: Young people with CFS/ME can benefit from better educational adaptations and increased social interaction with peers. From the participants' view, factors that limit learning and socialisation include a lack of knowledge about CFS/ME among teachers and school personnel, expectations from teachers of doing more than they could manage at school, feeling alone coping with the disease and not recognising their own limitations regarding what they are able to do. Suggested factors perceived to enhance learning and socialisation were a better understanding of the disease among school personnel and peers, suitable educational adaptations and being able to socialise with peers. 

3. Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome 

Ruiz-Pablos Manuel, Paiva Bruno, Montero-Mateo Rosario, Garcia Nicolas, Zabaleta Aintzane 
Frontiers in Immunology 12; 4637 


Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) affects approximately 1% of the general population. It is a chronic, disabling, multi-system disease for which there is no effective treatment. This is probably related to the limited knowledge about its origin.  

Here, we summarized the current knowledge about the pathogenesis of ME/CFS and revisit the immunopathobiology of Epstein-Barr virus (EBV) infection.  

Given the similarities between EBV-associated autoimmune diseases and cancer in terms of poor T cell surveillance of cells with EBV latency, expanded EBV-infected cells in peripheral blood and increased antibodies against EBV, we hypothesize that there could be a common etiology generated by cells with EBV latency that escape immune surveillance.  

Albeit inconclusive, multiple studies in patients with ME/CFS have suggested an altered cellular immunity and augmented Th2 response that could result from mechanisms of evasion to some pathogens such as EBV, which has been identified as a risk factor in a subset of ME/CFS patients. Namely, cells with latency may evade the immune system in individuals with genetic predisposition to develop ME/CFS and in consequence, there could be poor CD4 T cell immunity to mitogens and other specific antigens, as it has been described in some individuals.  

Ultimately, we hypothesize that within ME/CFS there is a subgroup of patients with DRB1 and DQB1 alleles that could confer greater susceptibility to EBV, where immune evasion mechanisms generated by cells with latency induce immunodeficiency.  

Accordingly, we propose new endeavors to investigate if anti-EBV therapies could be effective in selected ME/CFS patients. 

4. Moxibustion for Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis 

You J, Ye J, Li H, Ye W, Hong E.  
Evid Based Complement Alternat Med. 2021 Nov 11;2021:6418217.  


Objective: This review aimed at systematically evaluating the efficacy and safety of moxibustion for chronic fatigue syndrome (CFS). 

Methods: Relevant trials were searched in seven digital databases up to January 2021. After literature screening, data extraction, and literature quality evaluation, the included studies were meta-analyzed using RevMan 5.4 software. The evidence level was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). 

Results: Fifteen studies involving 1030 CFS participants were included. Meta-analyses showed a favorable effect of moxibustion on the total effective rate compared with acupuncture (OR = 4.58, 95%CI = [2.85, 7.35], P < 0.00001) and drugs (OR = 6.36, 95%CI = [3.48, 11.59], P < 0.00001). Moxibustion also appeared to significantly reduce fatigue severity measured by fatigue scale-14 (FS-14) (WMD = -2.20, 95% CI = [-3.16, -1.24], P < 0.00001) and fatigue assessment instrument (FAI) (WMD = -16.36, 95% CI = [-26.58, -6.14], P=0.002) compared with the control group. In addition, among the 15 included studies, only two studies reported adverse events related to moxibustion, and the symptoms were relatively mild. The quality of evidence based on the 15 included trials was assessed as moderate to very low. 

Conclusions: Based on limited evidence, moxibustion might be an effective and safe complementary therapy for CFS, which can be recommended to manage CFS. Because of the limited level of evidence in this review, further high-quality trials are still needed to confirm these findings. 

Long-COVID Research References   

  1. Post-COVID Syndrome symptoms, functional disability and clinical severity phenotypes in hospitalised and non-hospitalised individuals: a cross-sectional evaluation from a community COVID rehabilitation service 
  1. More Than 100 Persistent Symptoms of SARS-CoV-2 (Long COVID): A Scoping Review 
  1. Models of Care for Postacute COVID-19 Clinics: Experiences and a Practical Framework for Outpatient Physiatry Settings 
  1. Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction: What Do We Know? 
  1. Addressing the Long COVID Crisis: Integrative Health and Long COVID  
  1. Long-Term Evolution of Malnutrition and Loss of Muscle Strength after COVID-19: A Major and Neglected Component of Long COVID-19 
  1. Treatment of COVID-19 patients with quercetin: a prospective, single center, randomized, controlled trial 
  1. Non-hospitalised COVID-19 patients have more frequent long COVID-19 symptoms 
  1. Long Covid after Breakthrough COVID-19: the post-acute sequelae of breakthrough COVID-19  


Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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