Images of research to illustrate the weekly research roundup

ME/CFS Research Published 9 – 15 January 2024 

The weekly research round-up includes recent publications about ME/CFS and Long Covid. We highlight studies that have particularly caught our attention.


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

There have been four new ME/CFS studies and twenty-eight new Long Covid studies.  

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

Paper one (1) looks into the metabolic and immune alterations of Long Covid patients meeting the classification criteria for ME/CFS, due to a portion of Long Covid patients having symptoms which meet the diagnostic criteria for ME/CFS. 

This was primarily a metabolic study which is a large-scale comprehensive measurement of low-weight small molecules and metabolites within a biological specimen. These types of study are high output with a large amount of data being collected, and they rely heavily on statistical tests to find differences. More information on metabolomics can be found in the Medical Matters section of our website. 

As well as the laboratory analysis of blood samples, patients were assessed through questionnaires, such as: the De Paul Symptom Questionnaires (DSQ) and Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale questionnaire to determine symptom severity. 

The research included 60 PCR-confirmed SARS-CoV-2 individuals (plus healthy controls), and split these into four groups: 

  • Patients with LC exhibiting ME/CFS symptoms (LC) (n=30) 
  • Patients recovered from Covid-19 without any long lasting symptoms (R)(n=15) 
  • Patients with an acute Covid-19 infection (A) (n=15) 
  • Healthy controls who had not been exposed to Covid-19 (HC) (n=15). 

The results identified a range of alterations in the metabolomic pathways in the LC group compared to the other three groups, and these metabolic abnormalities were found to persist 12 months after the acute infection. The study also highlighted the fact that Long Covid disproportionately affects females more than males, with nearly 70% of LC patients in the study being female. 

There is a lot of detail given about the specific metabolic alterations in this study. Some of the further findings included: 

  • A total of 2584 metabolites were detected in the plasma samples. 
  • The Long Covid groups differed in its plasma metabolomics compared to the Recovered and Healthy Control groups. 
  • The Recovered groups also had a different metabolomic profile from Healthy Controls. 
  • Compared to HC’s, 18 pathways were significantly altered in LC patients. These alterations in metabolic pathways, resulted in a significant decline in the levels of aspartate, uracil, serine, sarcosine, arginine, dehydroalanine, thymine, and porphobilinogen in LC patients versus HCs. Other metabolites showed a significant increase: 5-Aminolevulinate, cysteate, putrescine, 4-Aminobutyraldehyde, kynurenine, serotonin, Formyl-5-hydroxykynurenamine, 5-Hydroxykynurenine, 2-Aminomuconate, xanthine, and 5-Aminolevulinate. 
  • A significant elevation in the plasma proinflammatory biomarkers such as the cytokine and autoantibodies (e.g. IL-1a, IL-6, TNF-a, Flt-1, and sCD14) but a reduction in ATP in LC patients compared to the controls and recovered groups. 
  • The results suggest that Long Covid severely affects the function of different organs, which could result in delayed tissue repair following infection.  
  • Metabolic alterations can be found in the recovered group 12 months after the acute infections. This means that the metabolic recovery period for infected individuals with Covid-19 is long lasting. 
  • A significant reduction in sarcosine and serine concentrations in Long Covid patients was found, which is also inversely correlated with depression, anxiety, and cognitive dysfunction scores. The authors therefore suggest that sarcosine and serine supplementations might have potential therapeutic implications in Long Covid patients. 
  • The authors also noted a correlation between their findings and previous ME/CFS research, such as reduction in glutamine and ornithine plasma levels, which suggests a disturbance in amino acid and nitrogen metabolism as previously reported in ME/CFS (Armstrong et al., 2012)

The biggest drawback of this research is that despite the link between ME/CFS and Long Covid being highlighted in this paper, an ME/CFS group was not included for comparison. 

Other limitations include: single-centred study (i.e. just one location), collection of samples at just one time point so we do not know how the metabolites vary over time, and all patients were infected with the Wuhan strain so we don’t know how results will differ with other covid strains. Furthermore, the metabolic analysis was restricted and did not include lipids which would allow a more detailed picture. 

Overall, this is a very comprehensive study. Metabolic studies like this give a lot of data which help to reveal metabolic alterations which could be fundamental to the disease course. We need more studies like this to understand disease mechanisms, help identify biomarkers and to point to treatments that can compensate for alterations found. 

You may also be interested in reading Paper two (2) in the Long Covid reference section, which is on the use of Amantadine for post Covid 19 fatigue. Dr Charles Shepherd has provided a comment on this study, which can be found here

ME/CFS Research References  

  1. Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome 
  1. Frequency and characteristics of chronic fatigue syndrome in multiple sclerosis patients at a university hospital in Eastern Saudi Arabia 
  1. Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview 
  1. Efficacy and Acceptance of Cognitive Behavioral Therapy in Adults with Chronic Fatigue Syndrome: A Meta-analysis 

Long-COVID Research References  

  1. Risks of digestive diseases in long COVID: evidence from a population-based cohort study 
  1. A randomized open-label clinical trial on the effect of Amantadine on post Covid 19 fatigue 
  1. Efficacy of dual-task augmented reality rehabilitation in non-hospitalized adults with self-reported long COVID fatigue and cognitive impairment: a pilot study 
  1. Characteristics of long COVID and the impact of COVID-19 vaccination on long COVID 2 years following COVID-19 infection: prospective cohort study 
  1. Randomised clinical trials with hyperbaric oxygen in COVID-19 and Long COVID : transcriptomic insights into benefits and harms 
  1. Self-Managing Symptoms of Long COVID: an Education and Strategies Research Protocol 
  1. Sustaining work ability amongst female professional workers with long COVID 
  1. Effectiveness of Internet-Based Group Supportive Psychotherapy on Psychic and Somatic Symptoms, Neutrophil-Lymphocyte Ratio, and Heart Rate Variability in Post COVID-19 Syndrome Patients 
  1. The new frontier: Clinical consequences of long COVID 
  1. Leveraging Mobile Health for Rehabilitation of Long-COVID Patients: A Scoping Review 
  1. Energy Management Education in Persons with Long COVID-Related Fatigue: Insights from Focus Group Results on Occupational Therapy Approach 
  1. Artificial Intelligence’s Transformative Role in Illuminating Brain Function in Long COVID Patients Using PET/FDG 
  1. Emerging Symptoms of and Institutional Support for Students with Long COVID in Higher Education 
  1. Post-COVID cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction: national prospective study 
  1. Post-COVID dysautonomias: what we know and (mainly) what we don’t know 
  1. Impact of sleep disruption on cognitive function in patients with post-acute sequelae of SARS-CoV-2 infection: Initial findings from a Neuro-COVID-19 clinic 
  1. Assessing the Quality of Life, Coping Strategies, Anxiety and Depression Levels in Patients with Long-COVID-19 Syndrome: A Six-Month Follow-Up Study 
  1. Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID 
  1. Explaining Long Covid: A pioneer cross sectional study supporting the endocrine hypothesis 
  1. Risk factors for experiencing Long-COVID symptoms: Insights from two nationally representative surveys 
  1. The role of α7 nicotinic acetylcholine receptors in post-acute sequelae of covid-19 
  1. Neutrophil degranulation, endothelial and metabolic dysfunction in unvaccinated long COVID patients 
  1. Evaluation of the learning effect on the six-minute walk distance in adults with long COVID 
  1. Long COVID-19 Symptoms in People with Dementia or Mild Cognitive Impairment 
  1. A biopsychosocial approach to persistent post-COVID-19 fatigue and cognitive complaints: results of the prospective multicenter NeNeSCo study 
  1. Vaccine Effectiveness Against Long COVID in Children 
  1. Intrinsic Capacity, COVID-19 infection and its long-term complications in older adults: a narrative review 
  1. Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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