Research Roundup

ME/CFS and Long Covid Research: 17 – 23 October 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

It’s been a quieter week for research. There have been three new ME/CFS studies and eighteen new Long Covid studies this week.

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

Paper one (1) is a drug trial for post-Covid ME/CFS patients in which clinical assessments and functional MRI scanning (fMRI) were used to determine whether drug therapy could improve their health status. The course of therapy received was coordination complex with succinate acid anion (CCSA), which is classed as being a “novel neuroprotective drug”.

This was a randomized, double-blind, placebo-controlled trial. This means that the patients were randomly split into the two groups either receiving the treatment drug or the placebo, where neither patients or researchers knew who was receiving which treatment. This prevents bias in the results. This study had 15 patients in each group, with treatment over 10 days.

The study involved clinical assessment, using multidimensional Fatigue Inventory (MFI-20) (which assesses general fatigue, physical fatigue, and reduced motivation), Montreal Cognitive Assessment (MoCA) (a rapid screening tool for mild cognitive dysfunction, such as attention and concentration) and Fatigue Assessment Scale (FAS-10). Furthermore, neuroimagaing was used at resting state fMRI and task-based fMRI.

The study demonstrated the potential effectiveness of receiving CCSA treatment for a range of symptoms, such as fatigue, asthenic syndrome and cognitive impairment. The results showed:

  • The main finding was that brain activation during cognitive tasks and brain functional connectivity between hubs of cognitive networks improved with CCSA administration.
  • Reduction in asthenic symptoms in the group of patients receiving CCSA.
  • Increase in functional cognitive status in the CCSA group, both clinically and shown on neuroimaging.
  • CCSA treatment altered rest and task based fMRI of the brain.
  • The patients receiving the CCSA drug had significantly lower MFI-20 scores following treatment, showing improved fatigue. Whereas the use of the MoCA scale only showed slight improvements.

There is a mix of terms in this study, with the use of both post-Covid chronic fatigue syndrome (as in the title) and post-Covid asthenic syndrome (which is used throughout the research). The term asthenia refers to physical weakness or a lack of energy, it is independent of any physical or mental strain. Asthenia can affect specific body parts, or it may affect the entire body. The symptoms of asthenia are commonly listed in ME/CFS research, but not asthenia syndrome. There is no clear diagnostic criteria used in this research, which limits what can be interpreted from the results. It is hard to truly assess which condition this study is referring too, as well as questioning the authors knowledge of these conditions. Furthermore, the link within the paper to explore more about asthenia syndrome links to anxiety neurosis, which is clearly a mistake!

The drug trialled in this research is registered under the trademark ‘Brainmax®’, which is marketed by the company Promomed, who also helped to fund this study. The authors claim that this did not effect the results or interpretation of the material published, but it is difficult to see how this did not introduce bias.

Other limitations of this study included: the small size, no healthy control group and also the limited duration of the study- we do not know the results in the longer term or if improvements will be permanent. This study used a balanced combination of clinical assessment questionnaires and neuroimaging, but it’s a shame that no blood biomarkers were measured for a more detailed clinical picture.

In conclusion, there are a number of limitations and questions over this study, which need to be addressed before CCSA can be considered as a potential treatment option.

ME/CFS Research References

1. A prospective randomized, double-blind placebo-controlled study to evaluate the effectiveness of neuroprotective therapy using functional brain MRI in patients with post-covid chronic fatigue syndrome

Tanashyan M, Morozova S, Raskurazhev A, Kuznetsova P.

Biomed Pharmacother. 2023 Oct 18;168:115723. [Epub ahead of print.]


Background and purpose: to assess executive network using resting-state fMRI and patterns of brain activation using task fMRI with a cognitive paradigm, against the background of taking the drug in comparison with placebo in patients with post-COVID asthenic syndrome.

Methods: The study employed a prospective, randomized, double-blind, placebo-controlled trial approach to assess the efficacy of utilizing functional MRI of the brain as a neuroprotective therapy for treating patients with chronic fatigue syndrome following COVID-19.

The study included 30 patients matched by sex and age with post-COVID asthenic syndrome. All patients were examined with MFI-20, MoCA, FAS-10 scales, MRI using a Siemens MAGNETOM Prisma 3 T scanner before and after a course of therapy with coordination complex with succinate acid anion (CCSA) or placebo (15 patients each) using resting state fMRI and with cognitive paradigm.

Results: The changes obtained as a result of the treatment of post-Covid asthenic syndrome demonstrated clinical superiority in the reduction of asthenic symptoms for the group of patients treated with CCSA (MFI-20 scores: -20·0 points in the CCSA group compared to -12 points in the placebo group, p = 0·043).

The data obtained also correlate with the analysis of task fMRI and resting state fMRI may indicate an increase in the functional cognitive status after a course of therapy with CCSA. Clinically, this correlates with a statistically significant improvement in the MoCA score (2 points in the CCSA group compared to 1 point in the placebo group, p < 0·05).

Conclusions: the study demonstrates the potential effectiveness of CCSA therapy in relation to a wide range of symptoms (chronic fatigue syndrome/ asthenic syndrome and cognitive impairment) in patients with post-COVID syndrome. The first time demonstrated the effectiveness of neuroprotective therapy after post-COVID asthenic syndrome with the use of high-tech neuroimaging techniques.

2. Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept

Luchting B, Behrends U, Eigner B, Stojanov S, Warlitz C, Haegele M, Neuwirth E, Mihatsch L, Richter HP.

Schmerz. 2023 Oct 20. [Article in German.] [Epub ahead of print.]


Background: Multimodal pain therapy usually take place in the context of group therapy lasting several weeks and is based on a generally activating approach. Due to the specificity of stress intolerance with postexertional malaise (PEM) in patients with postviral syndromes, physical as well as psychological overload must be urgently avoided in these cases; however, these aspects can only be insufficiently considered in current medical pain therapy concepts.

Methods: Summary of the current literature and presentation of clinical characteristics as well as presentation of a model project for a multimodal pain therapy in postviral syndromes with PEM.

Model concept: The presented model project describes a day clinic treatment setting for interdisciplinary multimodal pain therapy adapted to the individual resilience with minimization of the risk of strain-induced deterioration of the condition.

3. The importance of estimating prevalence of ME/CFS in future epidemiological studies of long COVID

Anna D. Grabowska, Francisco Westermeier, Luis Nacul, Eliana M. Lacerda, Nuno Sepulveda.

Frontiers in Public Health, Volume 11- 2023.


The end of the COVID-19 pandemic is generating a wide interest on long COVID (LC) (1), a heterogeneous medical condition known by many alternative names, such as the post-COVID-19 syndrome (2), the post-acute COVID-19 syndrome (3), and post-acute sequelae of SARS-CoV-2 infection (4), and persistent post-COVID-19 syndrome (5). This condition is a top priority in the current biomedical research agenda due to its great impact on public health (6).

The clinical manifestation of LC varies from mild and temporary symptoms, such as anosmia and ageusia, to highly debilitating and chronic fatigue and post-exertional malaise (PEM) (7). This spectrum of symptoms might be explained by immune dysregulation, microbiota dysbiosis, autoimmunity and immune priming, abnormal blood clotting and endothelial-related problems, and neurological signaling dysfunction, among other pathological mechanisms (1,8).

The real burden of LC remains elusive even though systematic reviews aggregate data from hundreds of studies and thousands of individuals (9–11). The underlying problems are the reliance on self-reporting of symptoms for the LC diagnosis and the challenge of conducting studies without any sources of sampling bias (10).

The same problems emerge in the few epidemiological studies on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (12,13). This disease remains without a specific biomarker (14), but might share some pathological mechanisms and symptoms with LC (4,15–18).

According to a recent meta-analysis (13), the pooled estimate of ME/CFS prevalence across multiple studies is 0.89% (95% CI =[0.60%–1.33%]). This estimate shows some variations according to gender (1.36% in women versus 0.86% in men), age (0.65% in adults versus 0.55% in children and adolescents), or study setting (0.76% in community-based study versus 0.63% in primary care studies. This disease inflicts dramatic individual and societal costs, such as health deterioration, reduced productivity, earnings and employment, mental health problems, and burnout (19).

Long-COVID Research References

  1. Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID-19 Testing Status Among Adults
  2. The Role of Long-term Low-dose Methylprednisolone Treatment on Long Covid Patients
  3. A National Evaluation of Outcomes in Long COVID Services using Digital PROM Data from the ELAROS Platform
  4. Serotonin reduction in post-acute sequelae of viral
  5. Youth experiences with and perspectives on long covid
  6. COVID-19 related headaches: epidemiology, pathophysiology, impacts, and management
  7. A qualitative study to explore children’s experience of having long-Covid
  8. Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome
  9. Return to work with long-COVID: An episodic disability and total worker health® analysis
  10. Just-in-time adaptive interventions for long covid related symptom cluster: a scoping review and a checklist for decision rules
  11. Prevalence and risk factors for persistent symptoms after COVID-19: a systematic review and meta-analysis
  12. Persistent post-COVID headache is associated with suppression of scale-free functional brain dynamics in non-hospitalized individuals
  13. Altered functional brain connectivity, efficiency, and information flow associated with brain fog after mild to moderate COVID-19 infection
  14. Prevalence of sleep disturbances in patients with long COVID assessed by standardised questionnaires and diagnostic criteria: A systematic review and meta-analysis
  15. Relevance of complement immunity with brain fog in patients with long COVID
  16. Improving Self-management for Long COVID: Using Double Diamond Model to Design A mHealth App
  17. Evaluation of late disorders as possible long-COVID and/or vaccination consequences
  18. Persistent Long-COVID Pain Symptoms Frequently Occur, Warrant Further Study

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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