Research Roundup: ME/CFS Research Published 11-17 December 2021

December 24, 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 11 – 17 December 2021  

It’s been another quite uninspiring week research wise. There have been four new research studies on ME/CFS but thirteen studies on Long Covid this week.  

We have highlighted two from the selection below:  

Paper one (1) is on the similar mechanisms involved in heat stroke and ME/CFS, in which both conditions involve inflammation and disturbance to the body’s homeostasis (maintaining stability and equilibrium). 

The paper lists a range of mechanisms which play a part in heat stroke, such as mitochondrial dysfunction, endothelial-cell injury, claiming that these are all well-documented in ME/CFS. Although this statement can be questioned,  as I’m not aware of all the mechanisms discussed being well documented. For example, I’m not aware of the evidence of splanchnic vasoconstriction (the reduced blood flow to the abdominal gastrointestinal organs including the stomach, liver etc). 

This paper is a review article, which draws comparisons, although I feel a lot of the comparisons are stretched, and maybe applied in a range of other medical conditions not just ME/CFS. Therefore, I do not feel this paper particularly adds to our understanding.  

Paper four (4) looks at the Polio vaccination and ME/CFS, where patients and healthy controls received the vaccination. This study showed no negative effects on ME/CFS symptoms with receiving the vaccination, however, the study cannot answer the question whether patients with ME/CFS are more susceptible to enterovirus(polio is caused by several different types of enterovirus) infection. 

You may also be interested in reading paper thirteen (13) in the Long Covid reference section. 

ME/CFS Research References and Abstracts  

1. Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 

Stanculescu Dominic, Sepúlveda Nuno, Lim Chin Leong, Bergquist Jonas 

Frontiers in Neurology 12: 2258 


We here provide an overview of the pathophysiological mechanisms during heat stroke and describe similar mechanisms found in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).  

Both conditions are characterized by disturbed homeostasis in which inflammatory pathways play a central role.  

Splanchnic vasoconstriction, increased gut permeability, gut-related endotoxemia, systemic inflammatory response, central nervous system dysfunction, blood coagulation disorder, endothelial-cell injury, and mitochondrial dysfunction underlie heat stroke. These mechanisms have also been documented in ME/CFS.  

Moreover, initial transcriptomic studies suggest that similar gene expressions are altered in both heat stroke and ME/CFS.  

Finally, some predisposing factors for heat stroke, such as pre-existing inflammation or infection, overlap with those for ME/CFS.  

Notwithstanding important differences – and despite heat stroke being an acute condition – the overlaps between heat stroke and ME/CFS suggest common pathways in the physiological responses to very different forms of stressors, which are manifested in different clinical outcomes.  

The human studies and animal models of heat stroke provide an explanation for the self-perpetuation of homeostatic imbalance centered around intestinal wall injury, which could also inform the understanding of ME/CFS. Moreover, the studies of novel therapeutics for heat stroke might provide new avenues for the treatment of ME/CFS.  

Future research should be conducted to investigate the similarities between heat stroke and ME/CFS to help identify the potential treatments for ME/CFS. 

2.What treatments work for anxiety and depression in children and adolescents with Chronic Fatigue Syndrome? An updated systematic review 

Philippa Clery, Alexander Royston , Katie Driver, Jasmine Bailey, Esther M Crawley, Maria Loades 

BMJ Open, Article in press 


Objectives: Children with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) experience a higher prevalence of depression and anxiety compared to age-matched controls. Our previous systematic reviews in 2015/16 found little evidence for effective treatment for children with CFS/ME with comorbid depression and/or anxiety. This review updates these findings. 
Design: A systematic review. We searched Cochrane library, Medline, Embase and PsychINFO databases from 2015-2020. We combined the updated results with our previous reviews in a narrative synthesis. 
Participants: Inclusion criteria: <18 years old; diagnosed with CFS/ME (using Centre for Disease Control, National Institute for Health and Care Excellence, or Oxford criteria); validated measures of depression and/or anxiety. 
Interventions: Observational studies or randomised controlled trials. 
Comparison: Any or none. 
Outcomes: Studies with outcome measures of anxiety, depression, or fatigue. 
Results: The updated review identified two studies. This brings the total number of paediatric CFS/ME studies with a measure of anxiety and/or depression since 1991 to 16. None of the studies specifically targeted depression, nor anxiety. One new study showed the Lightning Process (in addition to specialist care) was more effective at reducing depressive and anxiety symptoms compared to specialist care alone. Previous studies evaluated cognitive behavioural therapy (CBT); pharmacological interventions; and behavioural approaches. CBT-type interventions had most evidence for improving comorbid anxiety and/or depressive symptoms but varied in delivery and modality. Other interventions showed promise but studies were small and have not been replicated. 
Conclusion: Very few paediatric CFS/ME intervention studies have been conducted. This review update does not significantly add to what is known from previous reviews. The evidence is of poor quality and insufficient to conclude which interventions are effective at treating comorbid anxiety and/or depression in paediatric CFS/ME. 

3. Severity of COVID-19: Causes and Consequences — From Obesity to Chronic Fatigue Syndrome 

Arāja, Diāna, Rovīte, Vita, Murovska, Modra, Terentjeva, Anna, Vaidere, Diāna, Vecvagare, Katrīne and Vīksna, Ludmila.  

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences., vol.75, no.6, 2021, pp.411-416. 

In circumstances of COVID-19 epidemiological uncertainty, the causes and consequences of the disease remain important issues.  

The aim of this study was to investigate obesity as a potential predisposition and chronic fatigue syndrome (CFS) as a possible consequence of COVID-19.  

The study was conducted in two parts: a theoretical part, in which a literature review was performed, and an empirical part, in which COVID-19 patient survey data were analysed. To identify the main findings regarding the relationship between obesity and COVID-19, the literature review was focused on the investigation of systematic reviews and meta-analyses by three databases – Medline(via  PubMed),  Cochrane  COVID-19  Study  Register,  and  PROSPERO  (International prospective register of systematic reviews).  

The patient survey was performed to investigate the relationship between obesity and severity of the disease, as well as the presence of CFS symptoms in COVID-19 patients in Latvia.  

The main findings of the literature review showed that obesity increases the risk of hospitalisation, disease severity, clinical complications, poor outcomes, and mortality. The results of the patient survey showed that overweight and obesity were more critical factors for men (males) suffering with COVID-19 than for women (females) in Latvia.  

The patient group with obesity caused almost half of all hospitalisations. The research data assumed that CFS  patients  were  not  a  high-risk  group  for  COVID-19,  but  COVID-19  caused  CFS-like symptoms in patients and potentially increased the number of undiagnosed patients.  

In the context of further epidemiological uncertainty and the possibility of severe post-viral consequences, preventive measures are becoming increasingly important. 

4. Polio Vaccination and Chronic Fatigue Syndrome 

Smith AP and Thomas M 

Asian Journal of Research in Infectious Diseases 8(4): 43-49 

Background: Previous research has suggested that enteroviruses may be implicated in the development and persistence of Chronic Fatigue Syndrome (CFS). One method of investigating this topic has been to use a polio vaccination challenge, and a previous study showed that CFS patients had more shedding than healthy controls. There was no effect of the vaccination on the clinical condition or wellbeing of the CFS patients.  

Methods: In the previous study, the control group were more likely to have had a recent booster vaccination. This was controlled in the present study, where 18 CFS patients were randomly assigned to vaccination or placebo conditions. Nine healthy volunteers were also given the polio vaccination.  

Results: The results confirmed that vaccination had no negative effects on the CFS group. Although there was more virus shedding in the CFS polio group than in the control polio group, this difference was not significant.  

Conclusion: This study confirms that polio vaccination is not contraindicated in CFS patients but could not confirm that they are more susceptible to enterovirus infection. 

Long-COVID Research References   

  1. The contested meaning of “long COVID” – Patients, doctors, and the politics of subjective evidence 
  1. Controlling the Burden of COVID-19 by Manipulating Host Metabolism 
  1. Post-COVID-19 syndrome: Something to think about 
  1. Brain structure and function in people recovering from COVID-19 after hospital discharge or self-isolation: a longitudinal observational study protocol 
  1. Recovery From COVID-19 in Multiple Sclerosis: A Prospective and Longitudinal Cohort Study of the United Kingdom Multiple Sclerosis Register 
  1. Symptoms and quality of life at 1-year follow up of patients discharged after an acute COVID-19 episode 
  1. Long covid: research must guide future management 
  1. Symptoms and management of long COVID: A scoping review 
  1. Stellate ganglion block reduces symptoms of Long COVID: A case series 
  1. Cognitive sequelae of long COVID may not be permanent. A prospective study 
  1. Characterizing the COVID-19 Illness Experience to Inform the Study of Post-acute Sequelae and Recovery 
  1. Covid-19: Long covid symptoms among hospital inpatients show little improvement after a year, data suggest 
  1. Can l-carnitine reduce post-COVID-19 fatigue? 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent



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