Research Roundup: ME/CFS Research Published 27 November – 3 December 2021

December 9, 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 27 November – 3 December 2021  

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

There have been very few interesting ME/CFS papers this week, we have highlighted two from the selection below:  

Paper three (3) while not strictly on ME/CFS, this paper’s main focus is on long Covid, however, patients were assessed for ME/CFS and levels of fatigue as part of the assessment process. This article has gained a lot of media interest, such as here

This paper was a small study using 41 patients who underwent cardiopulmonary exercise testing (CPET) to define unexplained dyspnea (shortness of breath) in patients who had had a severe Covid infection.  

Results from the cardiopulmonary exercise testing (CPET) showed circulatory impairment and ventilatory abnormalities with dysfunctional breathing. However, the interesting and relevant part of this study assessed 46% of the patients with ongoing post-Covid symptoms to meet the criteria for ME/CFS, further concluding that many long Covid sufferers have ME/CFS. 

There are several limitations to this study, such as the small size and selection bias towards patients already known to have dyspnea.  

Paper four (4) is also on ME/CFS and long Covid, and looks at the use of supplements. The study used 79 ME/CFS patients and 9 long-covid patients, where they either received an oral therapy of nutraceutical, Meldonium and sodium dichloroacetate or an infusion therapy of magnesium sulphate together with multivitamins and essential amino acids for one month. 

The results from this study found that oral and infusion therapy had a beneficial effect on fatigue in the majority of ME/CFS patients- 2/3 patients fatigue improved. These results should be taken with caution, due to the small study and results need confirming in larger longer controlled trials. The ME Association has a leaflet summarising the scientific evidence on supplements, available here

You may also be interested in reading paper six (6) in the ME/CFS reference selection as well as three (3) and eight (8) in the Long-covid reference section. 

ME/CFS Research References and Abstracts  

1. The prevalence of chronic fatigue syndrome and depression in Guilan medical students in 2020 

Elahe Abdollahi, Robabeh Soleimani, Hamed Taherzadeh, Fatemeh Eslamdoust-Siahestalkhi 
Res Dev Med Educ. 2021;10(1): 25. 


Background: Chronic fatigue syndrome (CFS) and depression are specific mental disorders that can negatively affect college students’ social, occupational, and academic performance, especially medical students. This study aimed to investigate the prevalence of CFS and depressive symptoms and their relationship with medical students. 

Methods: This cross-sectional analytical study was conducted with 175 medical students at the Guilan University of Medical Sciences in 2020 in Guilan in the north of Iran. Three levels of medical students, including basic sciences and physiopathology, externship, and internship students, participated. A demographic information questionnaire, the Beck Depression Inventory-II (BDI-II), and the Chalder Fatigue Questionnaire (CFQ) were used to collect data. SPSS 22 was used to analyze the data, including Mann-Whitney, KruskalWallis, and Spearman tests. 

Results: The mean age of the participants was 23.92 ± 2.04 years. Of 175 participants, 50.9% were males. In all, 11.4% of subjects reported levels of CFS, and 38.8 % of them showed levels of depression. The rates of CFS and depressions were not associated with age, gender, marital status, educational level, geographic area, or student habitation (P>0.05). The use of cigarettes (P=0.002), alcohol, and substances (P<0.0001) showed a significant relationship with higher levels of CFS and depression scores. The relationship between the CFS score and depression was significant (r=0.523, P<0.0001). 

Conclusion: The prevalence of CFS and depression among medical students were 11.4% and 38.8%, respectively. There was a positive association between CFS and depression. Implementing screening policies is recommended, along with programs to help promote mental and physical health among students. 

2. Survey of people with Myalgic Encephalomyelitis (ME) to explore their use and experiences of physiotherapy services in the UK 

Clague-Baker N, Bull, M, Lesile K, Hilliard N 
Physiotherapy, P076, VOLUME 113, SUPPLEMENT 1, E101-E102, DECEMBER 01, 2021 


250,000 people live with Myalgic Encephalitis (ME) in the UK, this compares to 100,000 living with Multiple Sclerosis. In 2019, a survey by MEAction of 1906 people with ME, identified that over 50% of people who attended specialists ME clinics, employing physiotherapists, were unsatisfied with the services. People with ME (PwME) are also seen in regular musculoskeletal, community, neurological and paediatric physiotherapy services but the views of PwME related to these services are not known. The aim of this present survey, therefore, was to identify the experiences of PwME of physiotherapy services throughout all areas of physiotherapy practice. 

3. Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post–Coronavirus Disease 

Donna M. Mancini, Danielle L. Brunjes, Anuradha Lala, Maria Giovanna Trivieri, Johanna P. Contreras, Benjamin H. Natelson, 
J Am Coll Cardiol HF. 2021 Dec, 9 (12) 927–937 


Objectives: The authors used cardiopulmonary exercise testing (CPET) to define unexplained dyspnea in patients with post-acute sequelae of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (PASC). We assessed participants for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). 


Approximately 20% of patients who recover from coronavirus disease (COVID) remain symptomatic. This syndrome is named PASC. Its etiology is unclear. Dyspnea is a frequent symptom. 


The authors performed CPET and symptom assessment for ME/CFS in 41 patients with PASC 8.9 ± 3.3 months after COVID. All patients had normal pulmonary function tests, chest X-ray, and chest computed tomography scans. Peak oxygen consumption (peak VO2), slope of minute ventilation to CO2 production (VE/VCO2 slope), and end tidal pressure of CO2 (PetCO2) were measured. Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing. 


Eighteen men and 23 women (average age: 45 ± 13 years) were studied. Left ventricular ejection fraction was 59% ± 9%. Peak VO2 averaged 20.3 ± 7 mL/kg/min (77% ± 21% predicted VO2). VE/VCO2 slope was 30 ± 7. PetCO2 at rest was 33.5 ± 4.5 mm Hg. Twenty-four patients (58.5%) had a peak VO2 <80% predicted. All patients with peak VO2 <80% had a circulatory limitation to exercise. Fifteen of 17 patients with normal peak VO2 had ventilatory abnormalities including peak respiratory rate >55 (n = 3) or dysfunctional breathing (n = 12). For the whole cohort, 88% of patients (n = 36) had ventilatory abnormalities with dysfunctional breathing (n = 26), increased VE/VCO2 (n = 17), and/or hypocapnia PetCO2 <35 (n = 25). Nineteen patients (46%) met criteria for ME/CFS. 


Circulatory impairment, abnormal ventilatory pattern, and ME/CFS are common in patients with PASC. The dysfunctional breathing, resting hypocapnia, and ME/CFS may contribute to symptoms. CPET is a valuable tool to assess these patients. 

4. Boosting Health Recovery by Food Supplements: The Case of ME/CFS versus Post-Covid-19 Syndrome 

Frank Comhaire and Jan Pen 
J Clin Pharmacol Ther. 2021;2(3):JCPT-02-1022 


Background and objectives: Other than the direct impact of cardiopulmonary sequelae, COVID-19 disease may cause persistent signs and symptoms describes as post-COVID syndrome or long COVID. The clinical presentation and neuroimaging aspects of patients suffering from this condition are remarkably similar to those seen in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Inflammation, immune disorder and oxidative damage have been documented to cause metabolic deregulation with decreased glycolysis and impaired mitochondrial function.  

Purpose of the study: It is suggested that these alterations may be improved by the oral administration of a nutraceutical, Meldonium and sodium dichloroacetate (group designated as “oral treatment”; n=79) or intermittent intravenous infusions of magnesium sulphate together with multivitamins and essential amino acids (group designated as “infusion treatment”, n=18).  

Materials and methods: 97 patients suffering from ME/CFS (n=79) or post-COVID syndrome (n=9) were included in a pragmatic prospective open-label trial using either oral or infusion therapy for 1 month, and the effect of treatment was assessed by the Fatigue Severity Scale (FSS).  

Results: Upon interim analysis of 97 cases of ME/CFS and/or Post-COVID-19 syndrome therapeutic approach by either the oral or the infusion therapy was found to result in a reduction of the Fatigue Severity Scale (FSS) in two thirds of patients. The quotient of FSS after treatment divided by the FSS before treatment decreased by an average for all 97 cases by 14% within one month, with no difference between oral and infusion therapy (P=0.70), nor between the ME/CFS patient (mean quotient: 0.85, SD: 0.16) and the post-COVID cases (quotient: 0.87, SD: 0.16). Among the successful cases the FSS decreased by an average of 31%.  

Conclusion: Preliminary results of the oral and the infusion therapy suggest a similar beneficial effect on fatigue in a substantial proportion of patients suffering from ME/CFS or Post-COVID syndrome. The result should be confirmed in a controlled trial, while the long-term efficacy is presently being investigated in a larger group of patients. 

5. Experiences Among School Personnel and School Nurses on Educational Adaptations for Students With CFS/ME: A Qualitative Interview Study 

Similä WA, Rø TB, Nøst TH.  
Front Pediatr. 2021 Nov 11;9:756963.  


Introduction: Chronic fatigue syndrome (CFS/ME) is a disabling disease severely impacting school attendance, education, and social life in young students. Uncertainties surrounding CFS/ME etiology may impact the interpretation of CFS/ME in schools. Thus, school personnel need information from health care providers to make adequate adaptations to education and social life at school for these students.  

Objectives: To explore teachers, counselors, and school nurses' experiences with adapting education for students with CFS/ME aged 13-19 in secondary and high schools.  

Design: A qualitative study with focus group interviews and individual interviews performed face-to-face or digitally between November 2020 and March 2021. Data were analyzed using Systematic text condensation.  

Participants: Six teachers, two counselors, and four school nurses in secondary and high school participated.  

Results: Adapting education for students with CFS/ME was challenging, especially before the students received a diagnosis. The challenges were related to identifying the students' adaptational needs, maintaining a teacher-student relationship due to school absence, difficulties in maintaining continuity of education, and uncertainty regarding the diagnosis. Successful adaptations were related to quickly reacting to school absence, early referral to educational, psychological services, a close collaboration with the school management, and the development of digital teaching for students with CFS/ME. Interdisciplinary collaboration and a clear, constructive plan with adaptive measures, including maintained teacher-student communication and educational and social adaptations, may be useful in preventing the losses, young people, with CFS/ME experience.  

Conclusion: Early interdisciplinary collaboration to adapt education and social life at school for students with CFS/ME, may support teachers, counselors, and school nurses in their efforts to adapt education and prevent losses related to academic and social development in students with CFS/ME. 

6. COVID-19 and Chronic Fatigue Syndrome: An Endocrine Perspective 

Bansal R, Gubbi S, Koch CA.  
J Clin Transl Endocrinol. 2021 Dec 3:100284. [Epub ahead of print.] 


Patients recovering from COVID-19 may have persistent debilitating symptoms requiring long term support through individually tailored cardiopulmonary and psychological rehabilitation programs.  

Clinicians need to be aware about the likely long-term complications and their diagnostic assessments to help identify any occult problems requiring additional help.  

Endocrinological evaluations should be considered as part of the armamentarium in the management of such individuals with diligent cognizance about the involvement of the hypothalamo-pituitary-adrenal (HPA) axis, adrenals, and thyroid. 

Long-COVID Research References   

  1. Neurological, Psychological, and Cognitive Manifestations of Long-COVID 
  1. Long COVID from rheumatology perspective — a narrative review 
  1. Viral diseases and the brain: Long COVID puts the spotlight on how viral infections affect the brain 
  1. Who has long-COVID? A big data approach 
  1. Risk Factors Associated with Development and Persistence of Long COVID: A Cross-Sectional Study 
  1. COVID-19 Induced Immunosuppression resulting in Pulmonary Mucormycosis: A Long COVID sequalae 
  1. Exercise for counteracting post-acute COVID-19 syndrome in patients with cancer: an old but gold strategy? 
  1. SARS-CoV-2: Emerging Role in the Pathogenesis of Various Thyroid Diseases 
  1. Long term predictors of breathlessness, exercise intolerance, chronic fatigue and well-being in hospitalized patients with COVID-19: A cohort study with 4 months median follow-up 
  1. A model framework for projecting the prevalence and impact of Long-COVID in the UK 
  1. A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol 
  1. Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention 
  1. A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol 
  1. Autonomic dysfunction post-acute COVID-19 infection

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent



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