MEA Research Roundup

ME/CFS and Long Covid Research: 04  – 09 January 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 4  – 9 January 2023 

It’s been a slow start to January, with two new ME/CFS studies and thirteen new Long Covid studies. 

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

Paper two (2) investigates the use of red ginseng extract to improve chronic fatigue. This study uses a mice model of chronic fatigue syndrome, which was induced by stress. Three different concentrations (200, 400 or 600 mg/kg (plus control of just water)) of red ginseng extract were administered over 28 days (with 13 mice in each group). 

The two higher levels of red ginseng extract were seen to give the greatest improvements, such as reduced lactic acid. There was an improved skeletal muscle mitochondria function, with improved mitochondrial activity, decreased mitochondrial swelling and mitochondrial membrane permeability, increased mitochondrial biogenesis, thus ameliorating mitochondrial dysfunction. Although it should be noted that some of the more interesting analysis (i.e mitochondria morphology) was only carried out on 6 samples per treatment group, decreasing the strength of these results. 

Obviously, a major disadvantage of this study is the use of mice, a mouse model of tiredness is not the same as ME/CFS. It is also alluded that stress causes ME/CFS, whereas in reality it is not that simple. Some of this paper makes for hard reading, when talking about inducing chronic fatigue syndrome with cold water swimming and sleep deprivation. 

Mice are commonly used to study human biology due to their genetic and physiological similarities. Using mice as model organisms in studies has several advantages: their genome being 99% similar to the human genome while they also provide a cost-effective model due to their small size facilitating large scale/high throughput studies (Vandamme, 2014) (which this study wasn’t). The key facts of why mice are used in research can be found here

However, mice and humans have adapted to their environments differently making mice less reliable as models of human disease. The networks linking genes to disease are likely to differ between the two species. Using mice in biomedical research needs to take account of the evolved differences as well as the similarities between mice and humans (Perlman, 2016). 

Additionally, some of the terms in this study are a bit confused, with chronic fatigue and chronic fatigue syndrome being used interchangeably. A mouse model of chronic fatigue syndrome was used, however, the study focuses on relieving chronic fatigue. 

This study has shown that there is a benefit of taking red ginseng extract for mice, but whether these benefits translate to humans and those with ME/CFS is not known. I think these findings would be a lot more interesting if in humans, especially with the range of analysis that was conducted in this study. 

ME/CFS Research References and Abstracts  

1. Paediatric short fatigue questionnaire, a 4-item fatigue questionnaire for children 

Nap-van der Vlist MM, Vroegindeweij A, Hoefnagels JW, van der Ent CK, Swart JF, van de Putte EM, Nijhof SL.  

J Psychosom Res. 2022 Dec 24;165:111130. [Epub ahead of print] 


Objective: To investigate whether a paediatric Short Fatigue Questionnaire (pSFQ) assesses a valid construct for subjective fatigue, to assess its psychometric properties and provide a cut-off score for severe fatigue in children. 

Methods: The pSFQ consists of 4 items from the Checklist Individual Strength-8 (CIS-8). Data of previous studies using the CIS-8 were used to assess the pSFQ in healthy children (n = 316), children with chronic fatigue syndrome (n = 173), and children with a chronic disease (n = 442). All children were 12-18 years old. Confirmatory factor analysis (CFA) was performed, followed by Cronbach alpha's to investigate internal consistency, and Spearman's correlations to assess construct validity. With ROC analysis, we determined a cut-off score for severe fatigue and provide normative data on the pSFQ for children with and without a chronic disease. 

Results: CFA confirmed a one-factor model in the pSFQ representing subjective fatigue. Cronbach's alpha ranged from good to excellent (0.84-0.94), as did construct validity (-0.76 and – 0.87 for correlation with two other fatigue measurements). ROC analysis delivered a cut-off score of ≥21, with a sensitivity of 93.9% and specificity of 96.2% for severe fatigue. Normative data for children with and without a chronic disease showed similar patterns compared to other fatigue questionnaires. 

Conclusion: The pSFQ is a practical and reliable screening instrument for severe fatigue in children with and without a chronic disease, and effectively reduces the questionnaire length with 50% compared to the conventional CIS-8. 

2. Red ginseng extract improves skeletal muscle energy metabolism and mitochondrial function in chronic fatigue mice 

Zhang H, Zhao C, Hou J, Su P, Yang Y, Xia B, Zhao X, He R, Wang L, Cao C, Liu T, Tian J. 

Front Pharmacol. 2022 Dec 23;13:1077249. 


Background: Skeletal muscles are organs with high energy requirements, especially during vigorous exercise. Adequate mitochondrial function is essential to meet the high energy needs of skeletal muscle cells. Recent studies have reported that red ginseng can significantly improve chronic fatigue; however, the specific mechanism of action is still not clear. 

Methods: A chronic fatigue syndrome mouse model was developed using C57BL/6J mice through long-term compound stimulation of stress factors. Following this, the animals were orally administered 200, 400, or 600 mg/kg red ginseng extracts for 28 days. Skeletal muscle lactate acid, serum lactate dehydrogenase, urea concentrations, ATP level, mitochondrial membrane potential, activities of Na+-K+-ATPase and cytochrome c oxidase were determined using assay kits or an automatic biochemical analyser detection system.  

Skeletal muscle mitochondria morphology was observed using electron microscopy and the expression of p-AMPK, PGC-1α, ACO2 and complex I in skeletal muscle protein was determined by western blotting. 

Results: Oral administration of 400 or 600 mg/kg red ginseng extract in mice with chronic fatigue reduced lactic acid, lactate dehydrogenase and urea, rescued the density and morphology of skeletal muscle mitochondria, increased the activities of Na+-K+-ATPase and cytochrome c oxidase, and activated the AMPK/PGC-1α cascade pathway, resulting in improved skeletal muscle mitochondrial function by restoring ATP level, mitochondrial membrane potential, complex I and mitochondrial biogenesis. 

Conclusion: The anti-fatigue effects of red ginseng are partly related to its potent mitochondrial improving activity, including decreasing mitochondrial swelling and mitochondrial membrane permeability, increasing mitochondrial biogenesis, thus ameliorating mitochondrial dysfunction. 

Long-COVID Research References  

  1. Determinants of long COVID among adults hospitalized for SARS-CoV-2 infection: A prospective cohort study 
  1. Post-COVID-19 Syndrome: Incidence, Risk Factor, and the Most Common Persisting Symptoms 
  1. Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10-month follow-up 
  1. A machine learning-based phenotype for long COVID in children: an EHR-based study from the RECOVER program 
  1. Prevalence of long COVID-19 among healthcare workers: a systematic review and meta-analysis protocol 
  1. A Network Perspective on Neuropsychiatric and Cognitive Symptoms of the Post-COVID Syndrome 
  1. Long COVID: The long-term consequences of COVID-19 and the proposed pathophysiological mechanisms 
  1. A prospective follow-up on thyroid function, thyroid autoimmunity and long COVID among 250 COVID-19 survivors 
  1. Serum NGF and BDNF in Long-COVID-19 Adolescents: A Pilot Study 
  1. Post-COVID-19 Menstrual Symptom Disorders Relating to Anxiety and Long COVID-19 Symptoms 
  1. The contribution of gut-brain axis to development of neurological symptoms in COVID-19 recovered patients: A hypothesis and review of literature 
  1. Post-COVID-19 syndrome: nature of symptoms and associated factors 
  1. Post-acute sequelae of SARS-CoV-2 associates with physical inactivity in a cohort of COVID-19 survivors 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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