Research Roundup: ME/CFS Research Published 4-10 December 2021

December 17, 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 4 – 10 December 2021  

Research has picked up again this week. There have been nine new research studies on ME/CFS but thirteen studies on Long Covid this week.  

Despite there being nine studies this week, very few of them caught our eye. We have highlighted two from the selection below:  

Paper one (1) looks at functional limitations in ME/CFS and if this can be used as a biomarker (although not in the traditional sense of establishing a blood marker). This study provides a simple way to assess cognitive function using the Montreal Cognitive Assessment and for maintained function the Toulouse-Piéron test. The study found that maintaining attention after performing a test is a sensitive and reliable indicator for clinical suspicion of ME/CFS. 

The results from this study are confirmatory showing marked attention deficit in ME/CFS patients. Although these results need validating as almost all patients were taking medication. 

Paper four (4) is a systematic review, which investigates whether there is any association between psychological processes and behaviours and if these affect the immune-system. The paper found few associations, however emotional regulation, interpersonal function and sleep were associated with higher cytokine levels (essential molecule, part of the inflammatory process). The paper observes few consistent findings and a lack of studies to compare data between. 

You may also be interested in reading paper nine (9) which we missed from the weekly roundup back in September, which is on cardiovascular recovery after exercise (parasympathetic reactivation). 

ME/CFS Research References and Abstracts  

1.The maintained attention assessment in patients affected by Myalgic encephalomyelitis/chronic fatigue syndrome: a reliable biomarker? 

Murga I, Aranburu L, Gargiulo PA, Gómez-Esteban JC, Lafuente JV.  
J Transl Med. 2021 Dec 4;19(1):494. 


The maintained attention is the cause of great functional limitations in CFS/ME, a disease that mainly affects women in the central period of life.  

Cognitive function is explored using the Montreal Cognitive Assessment, the maintained attention using the Toulouse-Piéron test with which the Global Index of Attention and Perception (GIAP) is obtained, the fatigue using the visual analog scale and the perception of effort using the modified Borg scale.  

The final sample were 84 patients (66 women/18 men) who met diagnostic criteria (Fukuda-1994, Carruthers-2011) and 22 healthy controls (14 women/8 men).  

Most of patients maintain normal cognitive function, showing low or very low attention score in the 70% of patients with a marked cognitive fatigue compared to the control group (p < 0.05).  

There were no significant differences between genders in GIAP or fatigue for CFS/ME; however, sick women perceive cognitive effort higher than men.  

Deficits in sustained attention and the perception of fatigue, so effort after performing the proposed test are a sensitive and reliable indicator that allows us to substantiate a clinical suspicion and refer patients for further studies in order to confirm or rule out CFS/ME. 

2. Using Communities of Practice Theory to Understand the Crisis of Identity in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) 

Murray R, Turner L.  
Chronic Illn. 2021 Dec 6:17423953211064989. [Epub ahead of print.] 


Objective: To explore the crisis of identity in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) through the lens of Communities of Practice. 

Methods: A closed Facebook group was created to gather qualitative data from participants diagnosed with CFS/ME (n = 22). Data were analysed using a theoretical thematic analysis. 

Results: The current research revealed the reality of enabling and disabling communities in the lived experience of CFS/ME and the role of participation in developing empowered identities. Learning how to be alongside CFS/ME aligned with participants' experiences of purpose and meaning. New identities may be developed which are not centrally defined by loss or stigma. 

Discussion: Participation in supportive communities enables CFS/ME identities to emerge as a platform for positive change. Engaging with the CFS/ME virtual community may be a way for both families and health professionals to reflect on current practice. 

3. Associations Between Psychological and Immunological Variables in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review 

Raanes EFW, Stiles TC.  
Front Psychiatry. 2021 Nov 23;12:716320.  


Background: Little emphasis has been given to the fact that various psychological processes and behaviors in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) have neural correlates that affect-and are affected by-the immune system. The aim of this paper is to provide a systematic review of the literature on cross-sectional and longitudinal associations between psychological and immunological variables/changes in CFS/ME.  

Methods: The systematic literature search was conducted on Dec 10, 2020 using PubMed. Original research studies investigating associations between a predefined set of psychological and immunological variables in CFS/ME were included. Specifically, the review was focused on studies examining the following psychological variables: executive function, emotion regulation, interpersonal function, sleep, mental health, anxiety, depression, and/or other psychiatric symptoms. In terms of immunological variables, studies investigating interleukin (IL)-1, IL-2, IL-4, IL-6, tumor necrosis factor (TNF), CD4+, and/or CD8+ were included. Besides original research papers, other potentially relevant papers (e.g., literature reviews) were carefully read and reference lists were checked in order to identify any additional relevant studies. Available data was summarized in text and tables.  

Results: The literature search identified 897 potentially relevant papers. Ultimately, 14 studies (807 participants in total) were included in the review of which only two were longitudinal in nature. The review indicated that executive function is associated with IL-1 and IL-6, and interpersonal function is associated with IL-6 and TNF-α. Further, the available data suggested that emotion regulation is associated with IL-2 and sleep is associated with IL-1, IL-6, TNF-α, and IL-2. Interestingly, poorer emotion regulation, interpersonal function, and sleep have all been found to be associated with higher cytokine levels. Executive function has shown both positive and negative relationships with cytokines and among these psychological constructs, it is also the only one that has been found to be associated with CD4+ and CD8+ counts/percentages.  

Conclusions: Correlations exist between psychological and immunological variables in CFS/ME. However, there are few consistent findings and there is almost a complete lack of longitudinal studies. This review points to a gap in existing CFS/ME research and hopefully, it will inspire to the generation of innovative, psychoneuroimmunological hypotheses within the CFS/ME research field. 

4. Testing a newly developed activity pacing framework for chronic pain/fatigue: a feasibility study 

Antcliff D, Keenan AM, Keeley P, Woby S, McGowan L.  
BMJ Open. 2021 Dec 8;11(12):e045398.  


Objectives: To test the feasibility of using a new activity pacing framework to standardise healthcare professionals' instructions of pacing, and explore whether measures of activity pacing/symptoms detected changes following treatment. 

Design: Single-arm, repeated measures study. 

Setting: One National Health Service (NHS) Pain Service in Northern England, UK. 

Participants: Adult patients with chronic pain/fatigue, including chronic low back pain, chronic widespread pain, fibromyalgia and chronic fatigue syndrome/myalgic encephalomyelitis. 

Interventions: Six-week rehabilitation programme, standardised using the activity pacing framework. 

Outcome measures: Feasibility was explored via patients' recruitment/attrition rates, adherence and satisfaction, and healthcare professionals' fidelity. Questionnaire data were collected from patients at the start and end of the programme (T1 and T2, respectively) and 3 months' follow-up (T3). Questionnaires included measures of activity pacing, current/usual pain, physical/mental fatigue, depression, anxiety, self-efficacy, avoidance, physical/mental function and quality of life. Mean changes in activity pacing and symptoms between T1-T2, T2-T3 and T1-T3 were estimated. 

Results: Of the 139 eligible patients, 107 patients consented (recruitment rate=77%); 65 patients completed T2 (T1-T2 attrition rate=39%), and 52 patients completed T3 (T1-T3 attrition rate=51%). At T2, patients' satisfaction ratings averaged 9/10, and 89% attended ≥5 rehabilitation programme sessions. Activity pacing and all symptoms improved between T1 and T2, with smaller improvements maintained at T3. 

Conclusion: The activity pacing framework was feasible to implement and patients' ability to pace and manage their symptoms improved. Future work will employ a suitable comparison group and test the framework across wider settings to explore the effects of activity pacing in a randomised controlled trial. 

5. Graded exercise therapy for ME/CFS: finding consensus between the royal colleges, patients, and researchers 

Brown SI.  
BMJ. 2021 Dec 8;375:n3026. 

No abstract available 

6. Nationwide epidemiological characteristics of chronic fatigue syndrome in South Korea 

Lim EJ, Lee JS, Lee EJ, Jeong SJ, Park HY, Ahn YC, Son CG.  
J Transl Med. 2021 Dec 7;19(1):502.  


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 South 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. 

7. A Botanical Product Containing Cistanche and Ginkgo Extracts Potentially Improves Chronic Fatigue Syndrome Symptoms in Adults: A Randomized, Double-Blind, and Placebo-Controlled Study 

Kan J, Cheng J, Hu C, Chen L, Liu S, Venzon D, Murray M, Li S, Du J.  
Front Nutr. 2021 Nov 26;8:658630. 


Dietary therapy may be beneficial in alleviating symptoms of chronic fatigue syndrome (CFS), a disorder that is characterized by extreme fatigue and other symptoms, but the cause of which remains unclear.  

The aim of this study was to evaluate the protective effect of a botanical product containing cistanche (Cistanche tubulosa [Schenk] Wight) and ginkgo (Ginkgo biloba L.) extracts on adults with CFS in a randomized, double-blind, placebo-controlled clinical trial.  

A total of 190 subjects (35-60 years old, non-obese) with CFS were randomized to receive one tablet of a low dose (120-mg ginkgo and 300-mg cistanche), a high dose (180-mg ginkgo and 450-mg cistanche) or a placebo once daily for 60 days.  

Blood samples and responses on the Chalder fatigue scale (CFQ 11), the World Health Organization's quality of life questionnaire (WHOQOL), and the sexual life quality questionnaire (SLQQ) were collected at baseline and post-intervention.  

CFS symptoms of impaired memory or concentration, physical fatigue, unrefreshing sleep, and post-exertional malaise were significantly improved (p < 0.001) in both of the treatment groups.  

The botanical intervention significantly decreased physical and mental fatigue scores of CFQ 11 and improved WHOQOL and SLQQ scores of the subjects (p < 0.01).  

Levels of blood ammonia and lactic acid in the treatment groups were significantly lower than those of the placebo group (low-dose: p < 0.05; high-dose: p < 0.01).  

In addition, the change in lactic acid concentration was negatively associated with the severity of CFS symptoms (p = 0.0108) and was correlated with the change in total physical fatigue score of the CFQ (p = 0.0302). Considering the trivial effect size, the results may lack clinical significance.  

In conclusion, this botanical product showed promising effects in ameliorating the symptoms of CFS. Clinical trials with improved assessment tools, an expanded sample size, and an extended follow-up period are warranted to further validate the findings. 

8. Small heart and single coronary artery in a young patient with chronic fatigue syndrome: a case report 

Cristina Poleggi, Silvia Perfetti, Davide Restelli, Alessia Perna, Rocco Donato, Gianluca Di Bella 
European Heart Journal Supplements, Volume 23, Issue Supplement_G, December 2021, suab133.018 


Aims: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a clinically defined condition reported mostly in adults, characterized by fatigue and unexplained aspecifical symptoms. Patients with CFS/ME frequently have reduced stroke volume with an inverse relation between cardiac output and post-exertional malaise severity. We describe a rare case of a young man affected by CFS/ME, small heart, and anomalous anatomy of left main coronary artery (LMCA). 

Methods and results: A 19-year-old Caucasian male referred to our clinic complaining weakness, lack of concentration, and sleepiness. He suffered by CFS/ME, D hypovitaminosis, inflammatory bowel disease, and exocrine pancreas insufficiency.  

Blood tests revealed no pathological findings. Faecal exams documented intestinal dysbiosis and low pancreatic elastase.  

He was treated with oxygen-ozone rectal insufflations and probiotics. Physical examination was unremarkable.  

Electrocardiogram showed normal sinus rhythm. Echocardiogram revealed reduced diameters of the left ventricle (LV), normal aortic root dimensions and, in a five-chamber apical view, a binary structure that seemed to cross the aorta perpendicularly. Cardiac magnetic resonance (CMR) found reduced LV stroke volume (34 ml/m2) and end-diastolic volume (57 ml/m2) together with reduced end-diastolic wall mass (51 g/m2). Right ventricle volumes were reduced too.  

In addition, the exam confirmed the anomalous origin of LMCA stemming from the proximal segment of right coronary artery and following a retro-aortic course.  

Mechanism of CFS/ME remains unknown, although various factors have been implicated, including immune activation, chronic viral infection, and emotional disorders.  

A considerable number of patients affected by CFS has an anatomically small heart. Small heart syndrome, in fact, may contribute to the onset of CFS/ME.  

Previous studies hypothesized that clinical manifestations of CMS/ME were caused by reduced venous return, cardiac output, and heart mass, together with decreased arterial oxygen saturation. Single coronary artery is an uncommon congenital anatomic abnormality identified by a single coronary ostium giving rise to all arteries supplying the heart. 

Thus, we reported a rare case of a very young man affected by chronic fatigue syndrome and small heart, investigated not only with echocardiogram but also with CMR, not often used in this clinical setting. More, we found an anomalous origin of LMCA. From literature, it’s not reported any cases of a patient including these three rare conditions (CFS/ME, small heart, and single coronary artery). 

Conclusions: This case highlights that CFS/ME together with small heart is a condition possible also in young people. More studies and reports could be necessary to better define the association between cardiac congenital anomalies and CFS/ME. 

9. Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 

Van Oosterwijck, J.; Marusic, U.; De Wandele, I.; Meeus, M.; Paul, L.; Lambrecht, L.; Moorkens, G.; Danneels, L.; Nijs, J.  
J. Clin. Med.2021, 10, 4527. 


Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients.  

Although severe exercise intolerance is one of the core features of ME/CFS, little attempts have been made to study ANS responses to physical exercise. Therefore, impairments in ANS activation at rest and following exercise were examined using a case-control study in 20 ME/CFS patients and 20 healthy people.  

Different autonomous variables, including cardiac, respiratory, and electrodermal responses were assessed at rest and following an acute exercise bout.  

At rest, parameters in the time-domain represented normal autonomic function in ME/CFS, while frequency-domain parameters indicated the possible presence of diminished (para)sympathetic activation. Reduced parasympathetic reactivation during recovery from exercise was observed in ME/CFS.  

This is the first study showing reduced parasympathetic reactivation during recovery from physical exercise in ME/CFS. Delayed HR recovery and/or a reduced HRV as seen in ME/CFS have been associated with poor disease prognosis, high risk for adverse cardiac events, and morbidity in other pathologies, implying that future studies should examine whether this is also the case in ME/CFS and how to safely improve HR recovery in this population. 

Long-COVID Research References   

  1. Spectrum of SARS-CoV-2-Related Clinical Syndromes in Children: A Year in the Life 
  1. How Common is Long COVID in Children and Adolescents? 
  1. Proposal of a food supplement for the management of post-COVID syndrome 
  1. Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies 
  1. Long COVID-The New “Invisible” Illness: How School Nurses Can Support the Nursing and Educational Teams for Student Success 
  1. Incidence and risk factors of long COVID in the UK: a single-centre observational study 
  1. Persistence of Symptoms After Discharge of Patients Hospitalized Due to COVID-19 
  1. Do vaccines protect against long COVID? What the data say 
  1. Coronapod: vaccines and long COVID, how protected are you? 
  1. Promotion of non-evidence-based therapeutics within patient-led Long COVID support groups 
  1. Neuro-COVID-19 
  1. Proposed subtypes of post‐COVID‐19 syndrome (or long‐ COVID) and their respective potential therapies 
  1. Proposal of a food supplement for the management of post-COVID syndrome

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent



Shopping Basket