Research Roundup: ME/CFS Research Published 6 – 12 November 2021

November 19, 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 6 – 12 November 2021  

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

We have highlighted two papers on ME/CFS from the selection below: 

Paper three (3) investigates the use of immunoglobulin (IgG) therapy for ME/CFS. Immunoglobulins are a type of antibody and they are made by the white blood cells. This paper is co-authored by the ME Association’s honorary paediatric adviser, Dr Nigel Speight. 

This paper studied research trials conducted between 1990-1999, which resulted in four double-blind randomised placebo-controlled trials being reviewed where intravenous (IV) (via the vein) immunoglobulin was used. The paper lists the key difference and summaries the findings of each of these trails. 

Findings from this paper suggest that IV IgG treatment may have therapeutic value, especially where ME/CFS is well-characterised or severe. The paper stresses that there is a need for more research into IV IgG treatment and offering this treatment should be considered by doctors.  

However, it should be stressed that the new NICE guideline did review evidence for IV IgG treatment and there was not enough evidence for its safety or efficiency (see the ME Association comment on this paper here). As well as the fact that only four papers were reviewed in this paper there is some concern that this paper might raise false hopes for future treatments becoming available. Furthermore, other targeted treatments, such as rituximab, which aims to reduce inflammation and joint damage although initially promising were shown to have no benefit when further studies were carried out. 

The fourth paper (4) below is also a review this time focusing on the role of gut microbiota in ME/CFS. We also covered a paper on gut microbiomes last week (see here), gastrointestinal (GI) problems are common in ME/CFS. 

This review focuses on why the changes in gut microbiota (GM) may be found in ME/CFS patients, reviewing evidence on genetics and infections. This review finds ME/CFS patients to have: 

  • Altered microbiome 
  • Reduced microbial dysbiosis (microbial diversity) (nine papers which cover this are summarised) 
  • Increased gut permeability 
  • Oxidative stress and inflammation 

The review also looks at potential therapies which can be used to address the microbiota and related symptoms, such as probiotics, prebiotics, diet, and fecal microbiota transplantion (FMT)

The paper concludes that “the role of the gut microbiota in ME/CFS pathogenesis and disease development is still partially unclear and needs to be fully addressed to enable proper treatment of the disease” and that there is a need for larger studies. Furthermore, this review does not answer the question, are microbiome changes causing ME/CFS or are these changes caused by patients being ill.  

ME/CFS Research References and Abstracts  

1. mapMECFS: a portal to enhance data discovery across biological disciplines and collaborative sites 

Mathur R, Carnes MU, Harding A, Moore A, Thomas I, Giarrocco A, Long M, Underwood M, Townsend C, Ruiz-Esparza R, Barnette Q, Brown LM, Schu M. mapMECFS: a portal to enhance data discovery across biological disciplines and collaborative sites. J Transl Med. 2021 Nov 8;19(1):461. 


Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease which involves multiple body systems (e.g., immune, nervous, digestive, circulatory) and research domains (e.g., immunology, metabolomics, the gut microbiome, genomics, neurology). Despite several decades of research, there are no established ME/CFS biomarkers available to diagnose and treat ME/CFS. Sharing data and integrating findings across these domains is essential to advance understanding of this complex disease by revealing diagnostic biomarkers and facilitating discovery of novel effective therapies. 

Methods: The National Institutes of Health funded the development of a data sharing portal to support collaborative efforts among an initial group of three funded research centers. This was subsequently expanded to include the global ME/CFS research community. Using the open-source comprehensive knowledge archive network (CKAN) framework as the base, the ME/CFS Data Management and Coordinating Center developed an online portal with metadata collection, smart search capabilities, and domain-agnostic data integration to support data findability and reusability while reducing the barriers to sustainable data sharing. 

Results: We designed the mapMECFS data portal to facilitate data sharing and integration by allowing ME/CFS researchers to browse, share, compare, and download molecular datasets from within one data repository. At the time of publication, mapMECFS contains data curated from public data repositories, peer-reviewed publications, and current ME/CFS Research Network members. 

Conclusions: mapMECFS is a disease-specific data portal to improve data sharing and collaboration among ME/CFS researchers around the world. mapMECFS is accessible to the broader research community with registration. Further development is ongoing to include novel systems biology and data integration methods. 

2. Chronic Fatigue Syndrome and Occupational Status: A Retrospective Longitudinal Study 

Stevelink, S, Mark, K, Fear, N, Hotopf, M & Chalder, T  
Occupational Medicine. 


Aims: This paper explores socio-demographic, work and clinical characteristics that are associated with occupational status among patients who were assessed at baseline and a follow-up point. 
Methods: Longitudinal data were assessed from patients affected by CFS who attended an outpatient CFS attending a specialist CFS treatment service between 2007 and 2014. The main outcome of interest, Employment status at baseline and follow-up, was available for 316 patients. Data were also included on gender, age, duration of CFS, fatigue severity, type and number of treatment sessions, coping strategies, functional impairment, common mental disorders and physical functioning. 
Results: Most patients were female (73%) and had been affected by CFS for longer than 2 years (66%). Patients were followed up for an average of 285 days and over this period 53% of patients who were working remained in employment. Of the patients who were not working at baseline, 9% had returned to work at follow-up. However, of those working at baseline, 6% were unable to continue to work at follow-up. Age, fatigue severity, functional impairment, cognitive and behavioural responses, and depressive symptoms impacted on a patients’ work status at follow-up. 
Conclusions: The findings indicated that it is possible for people with CFS to remain in work or return to work, despite having had a disabling illness. Work-related outcomes should be targeted in all people of working age. 

3. Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 

Brownlie H, Speight N.  
Healthcare. 2021; 9(11):1546. 


The findings of controlled trials on use of intravenous immunoglobulin G (IV IgG) to treat myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are generally viewed as representing mixed results.  

On detailed review, a clearer picture emerges, which suggests that the potential therapeutic value of this intervention has been underestimated.  

Our analysis is consistent with the propositions that:  

(1) IgG is highly effective for a proportion of patients with severe and well-characterised ME/CFS;  

(2) responders can be predicted with a high degree of accuracy based on markers of immune dysfunction.  

Rigorous steps were taken in the research trials to record adverse events, with transient symptom exacerbation commonly experienced in both intervention and placebo control groups, suggesting that this reflected the impact of participation on people with an illness characterised by post-exertional symptom exacerbation. Worsening of certain specific symptoms, notably headache, did occur more commonly with IgG and may have been concomitant to effective treatment, being associated with clinical improvement.  

The findings emerging from this review are supported by clinical observations relating to treatment of patients with severe and very severe ME/CFS, for whom intramuscular and subcutaneous administration provide alternative options.  

We conclude that:  

(1) there is a strong case for this area of research to be revived;  

(2) pending further research, clinicians would be justified in offering a course of IgG to selected ME/CFS patients at the more severe end of the spectrum.  

As the majority of trial participants had experienced an acute viral or viral-like onset, we further suggest that IgG treatment may be pertinent to the care of some patients who remain ill following infection with SARS-CoV-2 virus. 

4. The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications 

Varesi A, Deumer US, Ananth S, Ricevuti G.  
J Clin Med. 2021 Oct 29;10(21):5077. 


The well-known symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are chronic pain, cognitive dysfunction, post-exertional malaise and severe fatigue.  

Another class of symptoms commonly reported in the context of ME/CFS are gastrointestinal (GI) problems. These may occur due to comorbidities such as Crohn's disease or irritable bowel syndrome (IBS), or as a symptom of ME/CFS itself due to an interruption of the complex interplay between the gut microbiota (GM) and the host GI tract.  

An altered composition and overall decrease in diversity of GM has been observed in ME/CFS cases compared to controls.  

In this review, we reflect on genetics, infections, and other influences that may factor into the alterations seen in the GM of ME/CFS individuals, we discuss consequences arising from these changes, and we contemplate the therapeutic potential of treating the gut to alleviate ME/CFS symptoms holistically. 

5. Chronic Fatigue Syndrome: A Case Report Highlighting Diagnosing and Treatment Challenges and the Possibility of Jarisch–Herxheimer Reactions If High Infectious Loads Are Present 

Straub RK, Powers CM. 
Healthcare. 2021; 9(11):1537. 


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multi-system disease with no cure and no FDA-approved treatment. Approximately 25% of patients are house or bedbound, and some are so severe in function that they require tube-feeding and are unable to tolerate light, sound, and human touch.  

The overall goal of this case report was to  

(1) describe how past events (e.g., chronic sinusitis, amenorrhea, tick bites, congenital neutropenia, psychogenic polydipsia, food intolerances, and hypothyroidism) may have contributed to the development of severe ME/CFS in a single patient, and  

(2) the extensive medical interventions that the patient has pursued in an attempt to recover, which enabled her to return to graduate school after becoming bedridden with ME/CFS 4.5 years prior.  

This paper aims to increase awareness of the harsh reality of ME/CFS and the potential complications following initiation of any level of intervention, some of which may be necessary for long-term healing.  

Treatments may induce severe paradoxical reactions (Jarisch–Herxheimer reaction) if high infectious loads are present. It is our hope that sharing this case will improve research and treatment options for ME/CFS. 

Long-COVID Research References   

  1. A mixed-methods systematic review of post-viral fatigue interventions: Are there lessons for long Covid? 
  1. Female gender is associated with “long COVID” syndrome: a prospective cohort study 
  1. Statistical Issues and Challenges in Clinical Trials for COVID-19 Treatments, Vaccines, Medical Devices and Diagnostics 
  1. The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study 
  1. Evidence for impaired chronotropic responses to and recovery from 6-minute walk test in women with post-acute COVID-19 syndrome 
  1. Covid-19-Induced Dysautonomia: A Menace of Sympathetic Storm 
  1. Long-Term Evolution of Malnutrition and Loss of Muscle Strength after COVID-19: A Major and Neglected Component of Long COVID-19 
  1. Small Fiber Neuropathy Associated with SARS-CoV-2 Infection 
  1. The microvascular hypothesis underlying neurologic manifestations of long COVID-19 and possible therapeutic strategies 
  1. Post-COVID-19 assessment in a specialist clinical service: a 12-month, single-centre, prospective study in 1325 individuals 
  1. Post-COVID syndrome: the aftershock of SARS-CoV-2 
  1. Addressing Post-COVID Symptoms: A Guide for Primary Care Physicians 


Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent


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