MEA Research Roundup

ME/CFS and Long Covid Research: 14 – 20 June 2022 

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.

Audio Commentary by Dr Katrina Pears

ME/CFS Research Published 14 – 20 June 2022 

There have been four new ME/CFS studies and fourteen studies on Long Covid.  

There have been a number of biological studies this week. We have highlighted two of the studies below: 

Paper one (1) is on cryotherapy with stretching exercises, one of the co-authors of this paper is Professor Julia Newton who has provided us with a comment on this paper: 

“Cryotherapy is a treatment that is used frequently in Eastern Europe and Scandinavian countries, it provides a significant cold stimulus to the whole body by encouraging an individual to spend time in an extreme low temperature chamber.  It is recognised as being a stimulus to the autonomic nervous system, something that we have shown to be disordered in those with ME/CFS.   In view of the recognised value of low temperatures for autonomic dysregulation, we wanted to explore the feasibility of this in those with ME/CFS.  This was a pilot study to look at safety and potential efficacy of this form of treatment in ME/CFS and I am delighted to say that whole body cryotherapy appeared to be safe and of some benefit for those with ME/CFS. 

I (Julia Newton) have worked really closely with the team in Poland for a number of years now. Prof Zalewski has a lot of experience assessing and managing those with autonomic dysfunction and I encouraged him to consider ME/CFS as an autonomic disorder. My involvement was that I partly funded the study, developed with Prof Zalewski the protocol and supported the interpretation and analysis of the results.” 

The full study is easy to read, with several figures showing the methodology and improvements in cognitive function and fatigue. From the data presented in this study, cryotherapy is shown to be a potential treatment option, with many benefits, of course with more research and bigger studies needed. However, this research study is a follow-up of the previously published study by this group, published last June, so I am not sure how much of this is new data. Furthermore, if you wish to read a personal account of cryotherapy it can be read here

Paper two (2) is on anti-pathogen antibody levels, which aims to find evidence of an infectious trigger and/or evidence of immune dysregulation via plasma screening of 122 pathogen antigens.  

I personally felt this study would show some interesting findings, due to the fact that ME/CFS is often reported to be triggered by a viral infection, the fact a reasonable sized sample was used (59 ME/CFS patients and 44 healthy controls), and it was a high throughput study with a large range of pathogens investigated. Unfortunately, the findings from this research did not point to any one pathogen potentially triggering ME/CFS, or point to common pathogens being the cause of ME/CFS, with an absence of differences in antibody levels between ME/CFS and controls. 

The study, however, did find some interesting results when looking at sex-based differences, showing that male and female cases differ in their anti-pathogen immune profiles. Furthermore, the authors conclude from this that it is inappropriate to combine data from both sexes in serological investigations as opposite trends were seen between the two. 

You may also be interested in reading paper three (3) on intracellular nutritional differences, however, we can only access the abstract of this paper but this shows a number of interesting results with lower intracellular Vitamin B3 and manganese. 

ME/CFS Research References and Abstracts  

1. Combination of whole body cryotherapy with static stretching exercises reduces fatigue and improves functioning of the autonomic nervous system in Chronic Fatigue Syndrome 

Kujawski, S., Słomko, J., Godlewska, B.R. et al.  
J Transl Med20, 273 (2022). 


Background: The aim of this study was to explore the tolerability and effect of static stretching (SS) and whole body cryotherapy (WBC) upon fatigue, daytime sleepiness, cognitive functioning and objective and subjective autonomic nervous system functioning in those with Chronic Fatigue Syndrome (CFS) compared to a control population. 

Methods: Thirty-two CFS and eighteen healthy controls (HC) participated in 2 weeks of a SS + WBC programme. This programme was composed of five sessions per week, 10 sessions in total. 

Results: A significant decrease in fatigue was noted in the CFS group in response to SS + WBC. Some domains of cognitive functioning (speed of processing visual information and set-shifting) also improved in response to SS + WBC in both CFS and HC groups. Our study has confirmed that WBC is well tolerated by those with CFS and leads to symptomatic improvements associated with changes in cardiovascular and autonomic function. 

Conclusions: Given the preliminary data showing the beneficial effect of cryotherapy, its relative ease of application, good tolerability, and proven safety, therapy with cold exposure appears to be an approach worth attention. Further studies of cryotherapy as a potential treatment in CFS is important in the light of the lack of effective therapeutic options for these common and often disabling symptoms. 

2. Survey of Anti-Pathogen Antibody Levels in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome 

O’Neal, A.J.; Glass, K.A.; Emig, C.J.; Vitug, A.A.; Henry, S.J.; Shungu, D.C.; Mao, X.; Levine, S.M.; Hanson, M.R.  
Proteomes 2022, 10, 21. 


Infectious pathogens are implicated in the etiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) because of the occurrence of outbreaks of the disease.  

While a number of different infectious agents have been associated with the onset of ME/CFS, the identity of a specific organism has been difficult to determine in individual cases.  

The aim of our study is to survey ME/CFS subjects for evidence of an infectious trigger and/or evidence of immune dysregulation via serological testing of plasma samples for antibodies to 122 different pathogen antigens.  

Immune profiles were compared to age-, sex-, and BMI-matched controls to provide a basis for comparison.  

Antibody levels to individual antigens surveyed in this study do not implicate any one of the pathogens in ME/CFS, nor do they rule out common pathogens that frequently infect the US population.  

However, our results revealed sex-based differences in steady-state humoral immunity, both within the ME/CFS cohort and when compared to trends seen in the healthy control cohort. 

3. Intracellular Nutritional Biomarker Differences in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subjects and Healthy Controls 

Priya Krishnakumar, Camila Jaramillo, Shawn Kurian, Wendy Levy, Cara Milman, Nadine Mikati, Fatma Huffman, Maria Abreu, Amanpreet Cheema 
Current Developments in Nutrition, Volume 6, Issue Supplement_1, June 2022, Page 745 


Objectives: A comparison of the nutritional biomarkers between ME/CFS subjects and healthy controls (HC) was undertaken on secondary data collected from an IRB approved cross-sectional study in ME/CFS patients. 

Methods: ME/CFS participants were recruited per the 2018 revised Canadian Clinical Case Definition for ME/CFS along with age matched HCs. Self-reported information on demographics and supplement use was collected, and body mass index calculated. HEI was calculated from Willet FFQ and multiple day 24-hour recall data, and severity of fatigue measured by Multidimensional Fatigue Inventory (MFI). Lymphocyte transformation assay by SpectraCell Lab (Houston, TX) was employed for intracellular micronutrient status. A series of two-tailed Mann-Whitney U tests (ɑ = 0.05) were performed for the non-parametric data expressed as mean ± standard error of the mean. All statistical analyses were conducted in IBM SPSS Statistics version 25 (Armonk, NY). 

Results: Out of the 21 participants (11 ME/CFS and 10 HC), 82% of ME/CFS and 50% of HC were female. Higher fatigue scores were observed in ME/CFS (16.64 ± 1.36) than HC (10.78 ± 2.14). ME/CFS had better HEI scores (63.36 ± 13.44) than the HC (38.55 ± 12.29). However, despite better diet quality and supplementation, ME/CFS group showed lower intracellular Vitamin B3 and manganese (Mn) (86.3 ± 2.42 and 53.6 ± 2.81 respectively) but higher calcium (Ca) (57.5 ± 3.55) as compared to HC (97.2 ± 2.31, 64.5 ± 1.87 and 46.5 ± 0.96 respectively). 

Conclusions: The results align with the current literature on indications of mitochondrial dysfunction in ME/CFS. Reduced intracellular vit B3 provides suboptimal production of the NAD(P)(H)-cofactor family, thus affecting mitochondrial function and consequently energy production. The aberration in energy metabolism is compounded by other factors, such as reduced Mn but higher Ca intracellular levels seen in this study indicating disruptions in oxidative stress pathways, resulting in debilitating fatigue experienced by individuals with ME/CFS. 

4. Altered Effective Connectivity of Resting-State Networks by Tai Chi Chuan in Chronic Fatigue Syndrome Patients: A Multivariate Granger Causality Study 

Li Y, Wu K, Hu X, Xu T, Li Z, Zhang Y, Li K.  
Front Neurol. 2022 Jun 3;13:858833. 


Numerous evidence has shown that patients with chronic fatigue syndrome (CFS) have changes in resting brain functional connectivity, but there is no study on the brain network effect of Tai Chi Chuan intervention in CFS.  

To explore the influence of Tai Chi Chuan exercise on the causal relationship between brain functional networks in patients with CFS, 21 patients with CFS and 19 healthy controls were recruited for resting-state functional magnetic resonance imaging (rs-fMRI) scanning and 36-item Short-Form Health Survey (SF-36) scale assessment before and after 1month-long training in Tai Chi Chuan.  

We extracted the resting brain networks using the independent component analysis (ICA) method, analyzed the changes of FC in these networks, conducted Granger causality analysis (GCA) on it, and analyzed the correlation between the difference causality value and the SF-36 scale.  

Compared to the healthy control group, the SF-36 scale scores of patients with CFS were lower at baseline.  

Meanwhile, the causal relationship between sensorimotor network (SMN) and default mode network (DMN) was weakened.  

The above abnormalities could be improved by Tai Chi Chuan training for 1 month.  

In addition, the correlation analyses showed that the causal relationship between SMN and DMN was positively correlated with the scores of Role Physical (RP) and Bodily Pain (BP) in CFS patients, and the change of causal relationship between SMN and DMN before and after training was positively correlated with the change of BP score.  

The findings suggest that Tai Chi Chuan is helpful to improve the quality of life for patients with CFS. The change of Granger causality between SMN and DMN may be a readout parameter of CFS.  

Tai Chi Chuan may promote the functional plasticity of brain networks in patients with CFS by regulating the information transmission between them. 

Long-COVID Research References   

  1. Self-Reported Long COVID in the General Population: Sociodemographic and Health Correlates in a Cross-National Sample 
  1. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2 
  1. Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID 
  1. The presence of symptoms within 6 months after COVID-19: a single-center longitudinal study 
  1. A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study 
  1. Supporting Health for the Long Haul: a literature synthesis and proposed occupational therapy self-management virtual group intervention for return-to-work 
  1. Long-Term Symptoms of COVID-19: One-Year Follow-Up Study 
  1. Sarcopenia as potential biological substrate of long COVID-19 syndrome: prevalence, clinical features, and risk factors 
  1. Detecting anti–SARS-CoV-2 antibodies in urine samples: A noninvasive and sensitive way to assay COVID-19 immune conversion 
  1. Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study 
  1. Neurological long-COVID in the outpatient clinic: Two subtypes, two courses 
  1. The Role of Acupuncture for Long COVID: Mechanisms and Models 
  1. Long-COVID, metabolic and endocrine disease 
  1. The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent


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