MEA Research Roundup

ME/CFS and Long Covid Research: 29 November – 05 December 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 29 November – 5 December 2022 

There have been five new ME/CFS studies and fifteen new Long Covid studies. 

We have highlighted two of the ME/CFS studies: 

Paper two (2) looks at the influence of tai chi on functional brain connectivity. Tai chi is a moving meditation form, a series of gentle exercises are followed that creates harmony in the body and mind, it is a traditional Chinese martial art. 

This study recruited 20 ME/CFS patients and 20 healthy controls, who completed eight sessions of Tai Chi over one month. Before the first session and after the last eighth session participants underwent a clinical evaluation and a resting state functional MRI scan (fMRI). Machine learning and computer modelling was then used to study the different connections in the brain. The study also used three different questionnaires to evaluate the outcomes: Fatigue Scale-14 (FS-14), Pittsburgh Sleep Quality Index (PSQI) and MOS 36-item short-form health survey (SF-36). 

The study found that 60 of the functional connections looked at in the brain could discriminate between ME/CFS patients and healthy controls. Furthermore, tai chi was seen to improve ME/CFS symptoms (through decreased fatigue score), sleep quality and increase the connectivity in the brain of the left frontoparietal network (FPN) and default mode network (DMN). 

There are a number of things that stand out, which questions the strength of this study, for example: 

  • This study promotes exercise and quotes a number of references supporting exercise as an effective treatment, there is also no reference to the new NICE guideline. For example one quote from the paper says “the National Institute for Health and Care Excellence updated its guidelines to recommend exercise therapy for CFS”. 
  • The Fukuda criteria was used for diagnosis, which is heavily criticised in its use to diagnosis ME/CFS, especially when used in research. For example, problems with the Fukuda criteria include: post-exertional malaise (PEM) is not compulsory which leads to misdiagnosis, and it is not easy to use on a clinical level (a review on the contrasting case definitions has been written by Brown et al., 2013). 
  • This is also the first study I have come across where there is a tighter exclusion list for women, where those who were pregnant  and lactating women, but surprisingly also those who were menstruating during fMRI scanning were excluded. With these being excluded as hormones have been found to affect network dynamics in the brain. 
  • There is no mention of the ME severities in this study, and I feel this would only be suitable for those with milder ME/CFS. It is also not discussed in this paper if tai chi was conducted in the normal standing position or was adapted to be more chair based which would suit a wider range of people with ME/CFS, especially with orthostatic intolerance. 
  • Lastly, it could also be debated whether a study like this focusing on traditional Chinese medicine would ever find a negative outcome. 

I have previously participated in weekly tai chi classes a few years ago. Initially, I found these very hard work, especially on my arms. However, I did see my muscle strength increase, which was not measured in this study or any effects of post-exertional malaise (PEM), which seems to be commonly missed in these exercise programmes. For this study, twice weekly tai chi sessions were undertaken, and I would have found this too intense for my symptoms, which has not been considered in this study. However, it is nice to see the coupling of an exercise study with the use of fMRI scans. 

Paper three (3) looks at the tissue specific signature of human herpesvirus infection in those with ME/CFS, specifically focusing on HHV-6 and EBV (Epstein Barr virus), where reactivation has been linked to a number of diseases, including Alzheimer’s disease and ME/CFS. This study analyses postmortem tissue of three ME/CFS patients and 26 controls. 

The results show high viral load in the brain and neuronal tissues, including the spinal cord in ME/CFS patients, which was absent in the controls. The results suggest tissue specific locations for the active viruses. These results may also explain why a number of previous studies on HHV and EBV have provided disappointing results as a consequence of the mostly inaccessible sample locations. 

We have seen a number of studies of late which implicate the reactivation of human herpesviruses in ME/CFS and Long Covid, such as Apostolou et al., 2022 which we have previously covered in our weekly research roundup. In the Long Covid reference section this week, paper two (2) is even on this topic, but differing results were found. There is also currently an ongoing study looking at the reactivation of herpesviruses in ME/CFS,  the latest update can be read here.  

Results from this study are fascinating, unfortunately at the moment the full study is not available to read until it has undergone its final formatting (we will update when it becomes available). Studies like this are incredibly rare, therefore, expanding the cohort to verify the results is incredibly difficult. However, we sincerely thank those and their families who donated tissue for this research. 

You may also be interested in reading Paper four (4) which compares symptoms profiles of 42 ME/CFS patients and 73 Long Covid patients, finding a large amount of symptom overlap and greater impairment in those with ME/CFS. Information from the ME Association has also been referenced in this study which is good to see. 

In the Long Covid Reference section you may also be interested in Paper three (3) which shows the effectiveness of active pacing to manage post-exertional malaise (PEM)

ME/CFS Research References and Abstracts  

1. Severe myalgic encephalomyelitis/chronic fatigue syndrome in children and young people: a British Paediatric Surveillance Unit study 

Royston AP, Rai M, Brigden A, Burge S, Segal TY, Crawley EM.  

Arch Dis Child. 2022 Dec 1:archdischild-2022-324319. [Epub ahead of print.] 


Objectives: Primary objective: to determine the point prevalence and incidence rate of severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in children aged 5-16 years over 13 months. 

Secondary objectives: to describe the demographic features, symptoms, impact on activities of daily living, school attendance and time to diagnosis. 

Design: Prospective surveillance study conducted by the British Paediatric Surveillance Unit. Paediatricians was asked if they had assessed a child with severe ME/CFS (screening definition for prevalence and incidence: children (5-16 years) diagnosed with ME/CFS so severe that they are unable to attend school for more than 1 hour a week during the last 6 weeks of the school term). 

Participants: Patients 5-16 years of age, seen by paediatricians and two large ME/CFS specialist services across the UK and Ireland. 

Outcome measures: Paediatrician-completed questionnaires describing demographics, symptoms, function and treatment, (applying National Institute for Health and Care Excellence (NICE)-recommended criteria to assess severity of ME/CFS). Diagnosis of severe, probable severe or possible severe ME/CFS was made only with evidence of NICE-recommended screening blood tests. 

Results: 285 cases were reported, of which of which 33 were severe, 4 probable severe and 55 possible severe. Estimated prevalence was 3.2 per million children (95% CI 2.2 to 4.5). Including possible/probable severe ME/CFS gave 8.9 per million children (95% CI 7.2 to 11). The incidence rate was 0.90 per million children-years (95% CI 0.43 to 1.65) (1.97 per million children-years (95% CI 1.24 to 2.99)). Median age was 13 years and 58% of cases were female. Median time to diagnosis was 0.47 years. 

Conclusions: Although the incidence of children presenting with severe ME/CFS is low, all were very disabled. In addition, the majority receive little or no education. Paediatricians need to consider how to provide rehabilitation and education for these disabled young people. 

2. Tai Chi increases functional connectivity and decreases chronic fatigue syndrome: A pilot intervention study with machine learning and fMRI analysis 

Wu K, Li Y, Zou Y, Ren Y, Wang Y, Hu X, Wang Y, Chen C, Lu M, Xu L, Wu L, Li K. 

PLoS One. 2022 Dec 1;17(12):e0278415. 


Background: The latest guidance on chronic fatigue syndrome (CFS) recommends exercise therapy. Tai Chi, an exercise method in traditional Chinese medicine, is reportedly helpful for CFS. However, the mechanism remains unclear. The present longitudinal study aimed to detect the influence of Tai Chi on functional brain connectivity in CFS. 

Methods: The study recruited 20 CFS patients and 20 healthy controls to receive eight sessions of Tai Chi exercise over a period of one month. Before the Tai Chi exercise, an abnormal functional brain connectivity for recognizing CFS was generated by a linear support vector model. The prediction ability of the structure was validated with a random forest classification under a permutation test. Then, the functional connections (FCs) of the structure were analyzed in the large-scale brain network after Tai Chi exercise while taking the changes in the Fatigue Scale-14, Pittsburgh Sleep Quality Index (PSQI), and the 36-item short-form health survey (SF-36) as clinical effectiveness evaluation. The registration number is ChiCTR2000032577 in the Chinese Clinical Trial Registry. 

Results: 1) The score of the Fatigue Scale-14 decreased significantly in the CFS patients, and the scores of the PSQI and SF-36 changed significantly both in CFS patients and healthy controls. 2) Sixty FCs were considered significant to discriminate CFS (P = 0.000, best accuracy 90%), with 80.5% ± 9% average accuracy. 3) The FCs that were majorly related to the left frontoparietal network (FPN) and default mode network (DMN) significantly increased (P = 0.0032 and P = 0.001) in CFS patients after Tai Chi exercise. 4) The change of FCs in the left FPN and DMN were positively correlated (r = 0.40, P = 0.012). 

Conclusion: These results demonstrated that the 60 FCs we found using machine learning could be neural biomarkers to discriminate between CFS patients and healthy controls. Tai Chi exercise may improve CFS patients' fatigue syndrome, sleep quality, and body health statement by strengthening the functional connectivity of the left FPN and DMN under these FCs. The findings promote our understanding of Tai Chi exercise's value in treating CFS. 

3. Tissue specific signature of HHV-6 infection in ME/CFS 

Bhupesh K. Prusty, Francesca Kasimir, Danny Toomey, Zheng Liu, Agnes Kaiping and Maria Eugenia Ariza. 

Front. Mol. Biosci. 


First exposure to various human herpesviruses (HHVs) including HHV-6, HCMV and EBV does not cause a life-threatening disease. In fact, most individuals are frequently unaware of their first exposure to such pathogens. These herpesviruses acquire lifelong latency in the human body where they show minimal genomic activity required for their survival.  

We hypothesized that it is not the latency itself but a timely, regionally restricted viral reactivation in a sub-set of host cells that plays a key role in disease development.  

HHV-6 (HHV-6A and HHV-6B) and HHV-7 are unique HHVs that acquire latency by integration of the viral genome into sub-telomeric region of human chromosomes.  

HHV-6 reactivation has been linked to Alzheimer’s Disease, Chronic Fatigue Syndrome, and many other diseases. However, lack of viral activity in commonly tested biological materials including blood or serum strongly suggests tissue specific localization of active HHV-6 genome.  

Here in this paper, we attempted to analyze active HHV-6 transcripts in postmortem tissue biopsies from a small cohort of ME/CFS patients and matched controls by fluorescence in situ hybridization using a probe against HHV-6 microRNA (miRNA), miR-aU14.  

Our results show abundant viral miRNA in various regions of the human brain and associated neuronal tissues including the spinal cord that is only detected in ME/CFS patients and not in controls.  

Our findings provide evidence of tissue-specific active HHV-6 and EBV infection in ME/CFS, which along with recent work demonstrating a possible relationship between herpesvirus infection and ME/CFS, provide grounds for renewed discussion on the role of herpesviruses in ME/CFS. 

4. Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder? 

Azcue N, Gómez-Esteban JC, Acera M, Tijero B, Fernandez T, Ayo-Mentxakatorre N, Pérez-Concha T, Murueta-Goyena A, Lafuente JV, Prada Á, López de Munain A, Ruiz-Irastorza G, Ribacoba L, Gabilondo I, Del Pino R.  

J Transl Med. 2022 Dec 6;20(1):569.  


Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor? 

Objective: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition. 

Methods: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated. 

Results: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue. 

Conclusions: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19. 

5. Investigating undergraduate medical education on myalgic encephalomyelitis/ chronic fatigue syndrome 

Victoria Alice Reid, Nina Muirhead 

The British Student Doctor Volume 6, No. 1 (2022) 


Background and Objectives: ME/CFS is a poorly understood, highly stigmatised condition which significantly reduces patients’ quality of life. ME/CFS had been identified as a gap in many health professionals’ knowledge, therefore this research aims to explore the understanding of ME/CFS amongst UK medical students.  

Methods: An online survey developed using Redcap was distributed to participants who were recruited via social media or via medical societies' emails. The participants were undergraduate UK medical students.  

Results: 94 students completed the survey from more than 16 medical schools. 35% of the students did not know what ME/CFS is and 88% say that the disease has not been covered in their course so far. 89% of participants would like to learn more about ME/CFS, specifically through elearning and videos.  

Discussion: Participants were generally unaware of ME/CFS and its symptoms and had not received relevant teaching or exposure to the disease. Education on ME/CFS within undergraduate UK medical schools is currently inadequate and the interest expressed by students in this survey demonstrates a new teaching opportunity for UK medical schools. 

Long-COVID Research References  

  1. Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients 
  1. Impact of pre-existing chronic viral infection and reactivation on the development of long COVID 
  1. Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome 
  1. Reduced Muscle Strength in Patients with Long-COVID-19 Syndrome Is Mediated by Limb Muscle Mass 
  1. Post-COVID-19 syndrome/condition or long COVID: Persistent illness after acute SARS CoV-2 infection 
  1. Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome 
  1. Psychological consequences of long COVID: comparing trajectories of depressive and anxiety symptoms before and after contracting SARS-CoV-2 between matched long- and short-COVID groups 
  1. Pathophysiological mechanisms of thrombosis in acute and long COVID-19 
  1. Brain fog as a Long-term Sequela of COVID-19 
  1. Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems 
  1. A Scoping Review on Long COVID-19: Physiological and Psychological Symptoms Post-Acute, Long-Post and Persistent Post COVID-19 
  1. Psychological consequences of long COVID: comparing trajectories of depressive and anxiety symptoms before and after contracting SARS-CoV-2 between matched long- and shortCOVID groups 
  1. Cochrane “evidence relevant to” rehabilitation of people with post COVID-19 condition. What it is and how it has been mapped to inform the development of the World Health Organization recommendations 
  1. Clinical assessment of children with long COVID syndrome 
  1. The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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