MEA Research Roundup

ME/CFS and Long Covid Research: 28 February – 06 March 2023 

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 28 February – 6 March 2023 

It’s been a slower week for ME/CFS research with only three new ME/CFS studies but twenty-two new Long Covid studies. 

We have highlighted one of the ME/CFS studies in more detail below: 

Paper one (1) is a small study on brainstem volume changes in ME/CFS and Long Covid. This research used brain imaging through a strong MRI scanner, known as the 7-tesla. 

This study was small comparing the brainstem regions of 10 participants with ME/CFS, 8 with Long Covid and 10 healthy controls. 

Despite this being a small study, significant results were found showing abnormalities in the brainstem volume in ME/CFS and Long Covid, specifically: 

  • ME/CFS had larger volumes in several areas of the brainstem (whole and pons) compared to healthy controls. The pons is located at the base of the brain, between the medulla oblongata and the midbrain. It is part of the brainstem and central nervous system. 
  • Long Covid patients also had larger volumes in several areas of the brainstem, these were: whole brainstem, pons and superior cerebellar peduncle compared to healthy controls. 
  • No significant differences were found between the brain volumes in ME/CFS and Long Covid, demonstrating similar brainstem abnormalities. 
  • Brainstem volumes were also correlated to symptoms, such as pain and breathing difficulties. 

There are not many negatives that can be pointed out in the study design. However, it is a shame that there was a huge imbalance of females: males, for example in the healthy control group there were 7 females to 3 males. With such small sample sizes, the strength of the study could be improved by just using one sex, or a less unbalanced ratio. Longitudinal changes would also be interesting, especially seeing as the duration of illness will vary in ME/CFS and Long Covid. 

The researchers from Queensland Australia are highly active and experienced in the field of MRI scanning showing differences in the brains of people with ME/CFS. However, numerous studies they have conducted using neuroimaging have been small, so I am still waiting for a study which brings this all together. A summary of recent previous work from this group includes:  

  • Su et al., 2022 looked at the different networks in the brain (called the brain salience (SA) and default mode (DMN) networks) finding there is different neuropathology involved in ME/CFS patients who are diagnosed with the ICC criteria to those diagnosed with the Fukuda criteria (previous research roundup comment). 
  • Thapaliya et al., 2022a showed altered cortical volume and thickness in ME/CFS compared to controls (previous research roundup comment). 
  • Thapaliya et al., 2022b showing volumetric differences in the hippocampal subfields, again showing differences between patients diagnosed with the ICC Thapaliya or Fukuda criteria.  
  • Thapaliya et al., 2021 demonstrated neuronal microstructural changes in ME/CFS (alongside differences with diagnostic criteria). 
  • Thapaliya et al., 2020 used weighed MRI scans which produce different images (known as T1w/T2w) and these can be used to assess the microstructure of the brain. This research showed that this ratio increased in ME/CFS which is in contrast to other neurogenerative diseases, showing an increase in myelin and/or iron in the white matter and basal ganglia in ME/CFS. 

However, outside of this research group results for increased brainstem volume have not been so clear cut as shown by a review by Shan et al., 2020 (there is a table within the supplementary information detailing previous studies in this field) and studies by Alumutairi  et al., 2020. Although this may be due to advances in technology, as 7-Tesla is very advanced in its MRI scanning capabilities, as well as limitations in the design of the studies. Therefore, larger scale well designed studies are desperately needed. 

There are several papers of interest in the Long Covid reference section this week: 

  • Papers one (1), two (2) and three (3) are on gut microbiota, showing the increased risk of gastrointestinal disorders in Long Covid as well the microbiota’s role in disease development. 
  • Papers four (4) and five (5) are on covid-19 vaccination, showing that vaccination reduces the severity and duration of Long Covid. There is more coverage of the impact of covid-19 vaccination on long covid here and here
  • Paper six (6) suggests that Epstein-Barr virus (EBV) is associated with an increased risk in developing Long Covid. 

ME/CFS Research References and Abstracts  

1. Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients 

Thapaliya K, Marshall-Gradisnik S, Barth M, Eaton-Fitch N and Barnden L.  

Front. Neurosci. 17:1125208 


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients have overlapping neurological, autonomic, pain, and post-exertional symptoms.  

We compared volumes of brainstem regions for 10 ME/CFS (CCC or ICC criteria), 8 long COVID (WHO Delphi consensus), and 10 healthy control (HC) subjects on 3D, T1-weighted MRI images acquired using sub-millimeter isotropic resolution using an ultra-high field strength of 7 Tesla.  

Group comparisons with HC detected significantly larger volumes in ME/CFS for pons (p = 0.004) and whole brainstem (p = 0.01), and in long COVID for pons (p = 0.003), superior cerebellar peduncle (p = 0.009), and whole brainstem (p = 0.005).  

No significant differences were found between ME/CFS and long COVID volumes. In ME/CFS, we detected positive correlations between the pons and whole brainstem volumes with “pain” and negative correlations between the midbrain and whole brainstem volumes with “breathing difficulty.”  

In long COVID patients a strong negative relationship was detected between midbrain volume and “breathing difficulty.”  

Our study demonstrated an abnormal brainstem volume in both ME/CFS and long COVID consistent with the overlapping symptoms. 

2. A patient who recovered from post-COVID myalgic encephalomyelitis/chronic fatigue syndrome: a case report 

Oka T.  

BioPsychoSocial Medicine 17 (1): 8.  


Background: Some patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complain of persistent fatigue, dyspnea, pain, and cognitive dysfunction. These symptoms are often described as “long COVID”. Whether a patient with long COVID might develop myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is of interest, as is the treatment and management of ME/CFS in a post-COVID patient. Here I report a patient, who, after an infection with SARS-CoV-2, developed ME/CFS and recovered after treatment. 

Case presentation: The patient was a previously healthy 55-year-old woman who worked as a nurse and became ill with COVID-19 pneumonia. She then presented with severe fatigue, post-exertional malaise, dyspnea, pain, cognitive dysfunction, tachycardia, and exacerbation of fatigue on physical exertion, which persisted for more than 6 months after her recovery from COVID-19 pneumonia. She was bedridden for more than half of each day.  

The patient was treated from multiple perspectives, which included (1) instructions on eating habits and supplements; (2) cognitive and behavioral modifications for coping with physical, emotional, and cognitive fatigue; (3) instructions on conditioning exercises to improve deconditioning due to fatigue and dyspnea; and (4) pharmacotherapy with amitriptyline and hochuekkito, a Japanese herbal (Kampo) medicine. The patient made a complete recovery after completing the prescribed regimen and was able to return to work as a nurse. 

Conclusions: To the best of my knowledge, this is the first detailed report on a patient infected with SARS-CoV-2 followed by long COVID with the signs/symptoms of ME/CFS who recovered after treatment. I hope this case report will be helpful to health care practitioners by its presentation of some of the therapeutic options for alleviating disabling signs/symptoms in patients with post-COVID ME/CFS. 

3. Skin Temperature Circadian Rhythms and Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Role of Endothelin-1 in the Vascular Tone Dysregulation 

Cambras T, Zerón-Rugerio MF, Díez-Noguera A, Zaragozá MC, Domingo JC, Sanmartin-Sentañes R, Alegre-Martin J, Castro-Marrero J.  

International Journal of Molecular Sciences. 2023; 24(5):4835. 


There is accumulating evidence of autonomic dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, little is known about its association with circadian rhythms and endothelial dysfunction.  

This study aimed to explore the autonomic responses through an orthostatic test and analysis of the peripheral skin temperature variations and vascular endothelium state in ME/CFS patients.  

Sixty-seven adult female ME/CFS patients and 48 healthy controls were enrolled. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Postural changes in blood pressure, heart rate, and wrist temperature were recorded during the orthostatic test. Actigraphy during one week was used to determine the 24-h profile of peripheral temperature and activity. Circulating endothelial biomarkers were measured as indicators of endothelial functioning.  

Results showed that ME/CFS patients presented higher blood pressure and heart rate values than healthy controls in the supine and standing position (p < 0.05 for both), and also a higher amplitude of the activity rhythm (p < 0.01).  

Circulating levels of endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in ME/CFS (p < 0.05). In ME/CFS, ET-1 levels were associated with the stability of the temperature rhythm (p < 0.01), and also with the self-reported questionnaires (p < 0.001). This suggests that ME/CFS patients exhibited modifications in circadian rhythm and hemodynamic measures, which are associated with endothelial biomarkers (ET-1 and VCAM-1).  

Future investigation in this area is needed to assess dysautonomia and vascular tone abnormalities, which may provide potential therapeutic targets for ME/CFS. 

Long-COVID Research References  

  1. Long-term gastrointestinal outcomes of COVID-19 
  1. The role of the microbiota-gut-brain axis in post-acute COVID syndrome 
  1. Assessment of microbiota in the gut and upper respiratory tract associated with SARS-CoV-2 infection 
  1. Efficacy of first dose of covid-19 vaccine versus no vaccination on symptoms of patients with long covid: target trial emulation based on ComPaRe e-cohort 
  1. Effect of covid-19 vaccination on long covid: systematic review 
  1. Is exposure to epstein-barr virus a risk factor for long-covid? 
  1. COVID-19 long-term sequelae: Omicron versus Alpha and Delta variants 
  1. Could the fibromyalgia syndrome be triggered or enhanced by COVID-19? 
  1. Effect of Repetitive Transcranial Magnetic Stimulation on Long Coronavirus Disease 2019 with Fatigue and Cognitive Dysfunction 
  1. Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review 
  1. Conceptualising the episodic nature of disability among adults living with Long COVID: a qualitative study 
  1. Risk of new onset and persistent psychopathology in children with long-term physical health conditions: a population-based cohort study 
  1. The Very Long COVID: Persistence of Symptoms after 12–18 Months from the Onset of Infection and Hospitalization 
  1. Quality of life and ability to work of patients with Post-COVID syndrome in relation to the number of existing symptoms and the duration since infection up to 12 months: a cross-sectional study 
  1. Aging and long COVID-19 syndrome: what’s new in 2023? 
  1. Functional outcomes in post Covid-19 patients with persistent dyspnea: multidisciplinary approach 
  1. Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course 
  1. The role of immune activation and antigen persistence in acute and long COVID 
  1. Symptomatic Characteristics of Hypozincemia Detected in Long COVID Patients 
  1. “Long COVID”: the current state of the problem. Review of foreign scientific and medical publications 
  1. Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics 
  1. Demographic And Clinical Factors Associated With Long COVID 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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