Research Roundup: ME/CFS Research Published 9-15 October 2021

October 21, 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.

ME/CFS Research Published 9 – 15 October 2021  

There’s been very few interesting studies this week, with three new research studies on ME/CFS but thirteen studies on Long Covid. We have highlighted one paper below which is likely to be of the most interest to you: 

Paper two (2) looks at building on current evidence of ME/CFS being an illness which results from the dysfunctional autonomic nervous system (ANS). This study looked into the role of the central autonomic network (CAN) in the functioning of the ANS. The CAN is the intricate system of brainstem, subcortical, and cortical structures (outermost layer) in the brain. 

The study was relatively small using 34 ME/CFS patients and 34 healthy matched controls, where all the patient’s brain activity was recorded using an electroencephalogram (EEG). The data collected from brain activity recording was then analysed through a method called electromagnetic tomography (eLORETA), which can be used to determine which regions of the brain are activated during different states or mental tasks. 

Unfortunately, we cannot access the full paper, to explain the results in depth but the results from this study revealed topological differences between ME/CFS patients and healthy controls. These results suggest problems with homeostatic regulation (maintaining stability in different conditions) in ME/CFS. The authors hope that if their findings are verified, then treatments can be targeted to specific areas of the brain to help manage symptoms.  

You may also be interested in reading paper three (3) and ten (10) in the Long-COVID reference section of this roundup.  

Paper three (3) looks at the involvement of adrenal function in long-COVID , concluding that symptoms could be due to COVID-19 acting on the adrenal glands.  

Paper ten (10) looks at neurocognitive long COVID-syndrome analysing neuropsychological profiles and cerebral glucose metabolism. The paper concludes that it is likely that most neurology problems seen are due to the high level of fatigue, as no pathological changes in the brain were found. 

ME/CFS Research References and Abstracts  

1. Nationwide Epidemiological Characteristics of Chronic Fatigue Syndrome in South Korea 

Eun Jin Lim, Jin-Seok Lee, Eun-Jung Lee, Seok-Ju Jeong, Ho-Young Park, Yo-Chan Ahn, Chang-Gue Son 
ResarchSquare. Preprint 2021 


Background: Chronic fatigue syndrome (CFS) is a long-term disabling illness accompanied by medically unexplained fatigue. This study aimed to explore the epidemiological characteristics of CFS in South Korea. 

Methods: Using the nationwide medical records provided by the Korean Health Insurance Review & Assessment Service (HIRA), we analyzed the entire dataset for CFS patients diagnosed by physicians in Korea from January 2010 to December 2020. 

Results: The annual mean incidence of CFS was estimated to be 44.71 ± 6.10 cases per 100,000 individuals [95% CI: 40.57, 48.76], and the prevalence rate was 57.70 ± 12.20 cases per 100,000 individuals [95% CI: 49.40, 65.79]. These two rates increased by 1.53- and 1.94-fold from 2010 to 2020, respectively, and showed an increasing trend with aging and an approximately 1.5-fold female predominance. 

Conclusions: This study is the first to report the nationwide epidemiological features of CFS, which reflects the clinical reality of CFS diagnosis and care in South Korea. This study will be a valuable reference for studies of CFS in the future. 

2. Cortical autonomic network connectivity predicts symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) 

Zinn MA & Jason LA 

International Journal of Psychophysiology, 10: S0167-8760(21)00900-4. In Press, Journal pre-proof. [Epub ahead of print] 


  • The findings of this study contribute to the understanding of unexplained persistent and relapsing symptoms in patients with ME/CFS. 
  • eLORETA combined with graph theoretical analysis revealed topological changes in cortical autonomic network that were associated cognitive, affect, and somatomotor symptom clusters. 
  • Results suggest that cortical dysregulation with this network may serve as a therapeutic target for patients. 


Myalgic encephalomyelitis and chronic fatigue syndrome (ME/CFS) represents a significant public health challenge given the presence of many unexplained patient symptoms. Research has shown that many features in ME/CFS may result from a dysfunctional autonomic nervous system (ANS).  

We explored the role of the cortical autonomic network (CAN) involved in higher-order control of ANS functioning in 34 patients with ME/CFS and 34 healthy controls under task-free conditions.  

All participants underwent resting-state quantitative electroencephalographic (qEEG) scalp recordings during an eyes-closed condition. Source analysis was performed using exact low-resolution electromagnetic tomography (eLORETA), and lagged coherence was used to estimate intrinsic functional connectivity between each node across 7 frequency bands: delta (1–3 Hz), theta (4–7 Hz), alpha-1 (8–10 Hz), alpha-2 (10–12 Hz), beta-1 (13–18 Hz), beta-2 (19–21 Hz), and beta-3 (22–30 Hz). Symptom ratings were measured using the DePaul Symptom Questionnaire and the Short Form (SF-36) health survey.  

Graph theoretical analysis of weighted, undirected connections revealed significant group differences in baseline CAN organization. Regression results showed that cognitive, affective, and somatomotor symptom cluster ratings were associated with alteration to CAN topology in patients, depending on the frequency band.  

These findings provide evidence for reduced higher-order homeostatic regulation and adaptability in ME/CFS. If confirmed, these findings address the CAN as a potential therapeutic target for managing patient symptoms. 

3. Qualitative study of the acceptability and feasibility of acceptance and commitment therapy for adolescents with chronic fatigue syndrome 

Clery P, Starbuck J, Laffan A, Parslow RM, Linney C, Leveret J, Crawley E.  
BMJ Paediatr Open. 2021 Oct 1;5(1):e001139. 


Background: Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is disabling and relatively common. Although evidenced-based treatments are available, at least 15% of children remain symptomatic after one year of treatment. Acceptance and commitment therapy (ACT) is an alternative therapy option; however, little is known about whether it is an acceptable treatment approach. Our aim was to find out if adolescents who remain symptomatic with CFS/ME after 12 months of treatment would find ACT acceptable, to inform a randomised controlled trial (RCT) of ACT. 

Methods: We recruited adolescents (diagnosed with CFS/ME; not recovered after one year of treatment; aged 11-17 years), their parent/carer and healthcare professionals (HCPs) from one specialist UK paediatric CFS/ME service. We conducted semi-structured interviews to explore barriers to recovery; views on current treatments; acceptability of ACT; and feasibility of an effectiveness RCT. Thematic analysis was used to identify patterns in data. 

Results: Twelve adolescents, eleven parents and seven HCPs were interviewed. All participants thought ACT was acceptable. Participants identified reasons why ACT might be efficacious: pragmatism, acceptance and compassion are valued in chronic illness; values-focussed treatment provides motivation and direction; psychological and physical needs are addressed; normalising difficulties is a useful life-skill. Some adolescents preferred ACT to cognitive behavioural therapy as it encouraged accepting (rather than challenging) thoughts. Most adolescents would consent to an RCT of ACT but a barrier to recruitment was reluctance to randomisation. All HCPs deemed ACT feasible to deliver. Some were concerned patients might confuse ‘acceptance' with ‘giving up' and called for clear explanations. All participants thought the timing of ACT should be individualised. 

Conclusions: All adolescents with CFS/ME, parents and HCPs thought ACT was acceptable, and most adolescents were willing to try ACT. An RCT needs to solve issues around randomisation and timing of the intervention. 

Long-COVID Research References   

  1. Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP) 
  1. Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion 
  1. Possible Adrenal Involvement in Long COVID Syndrome 
  1. Biological and Psychological Factors Determining Neuropsychiatric Outcomes in COVID-19 
  1. Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started? 
  1. Preparing for the long-haul: Autonomic complications of COVID-19 
  1. Post-COVID-19 Syndrome 
  1. A public health approach to estimating the need for long COVID services 
  1. Long COVID: long-term effects? 
  1. Neuropsychological profiles and cerebral glucose metabolism in neurocognitive Long COVID-syndrome 
  1. Update on endothelial dysfunction in COVID-19: severe disease, long COVID-19 and pediatric characteristics 
  1. SARS-CoV-2 RNA in the Cerebrospinal Fluid of a Patient with Long COVID 
  1. Mild and Asymptomatic COVID-19 Convalescents Present Long-Term Endotype of Immunosuppression Associated With Neutrophil Subsets Possessing Regulatory Functions 

 Katrina Pears, Research Correspondent, ME Association  



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