Research Roundup

ME/CFS Research Published 10 – 16 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

There have been nine new ME/CFS studies and twenty-one new Long Covid studies this week.

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

Paper five (5) is an initial observational study of the use of repeated immunoadsorption for patients with Post- Covid ME/CFS. The research group conducting this study included investigators based out of Charité’s Fatigue Centre in Berlin, including Carmen Scheibenbogen, who we commonly see ME/CFS research from. 

Immunoadsorption (IA) is a selective apheresis method – a process that removes disease-provoking elements from blood. The theory surrounding the use of apheresis is that ‘micro-clots’ may be present in blood and could be causing persisting symptoms in Long Covid and ME/CFS. However, more research is needed before this invasive treatment can be recommended. There have been no clinical reports of clotting in ME/CFS. The ME Association’s views of apheresis can be read here.

The research team of this newly published study have already conducted two small scale proof-of-concepts studies on IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients (Tölle et al., 2020; Scheibenbogen et al., 2018). IgG or immunoglobulin G is a type of antibody, which is created and released by plasma B cells. These antibodies protect you against infection by “remembering” which germs you've been exposed to before. If those germs come back, your immune system knows to attack them.

This new study aimed to evaluate the efficacy of immunoadsorption in 10 post-Covid ME/CFS patients, its primary objective was to assess functional ability. For this, the study used three different sets of questionnaires to assess physical functioning: the Short-Form 36 Physical Function (SF36-PF) (reporting on health status), Bell Score (disability assessment scale), Fatigue Severity Scale (FFS) and weighted Canadian consensus Criteria (CCC) symptoms to assess the presence and severity of symptoms.

The main finding presented in this study is that: out of the 10 patients included, seven were defined as responding to treatment where there was an increase of between 10 to 35 points using the Short-Form 36 Physical Function (SF36-PF) four weeks after immunoadsorption. Some of the other findings included:

  • Four of the patients were found to respond rapidly to treatment with improvement in SF-36-PF scores.
  • Responders described improvements in core symptoms of pain, cognition and immunological symptoms.
  • Improvements in muscle pain and immune scores were significant after four weeks.
  • Improvements in cognitive score and headache were seen but these weren’t significant changes.
  • Several patients reported an initial worsening of fatigue and PEM, which could be attributed to the invasive treatment. Furthermore, FFS fatigue scores showed no significant change after four weeks.

A few things to note about this study:

  • This is a subset of patients, who had both been diagnosed with post-Covid ME/CFS and had elevated levels of ADRB2 autoantibodies. Therefore, we do not know how a wider cohort would respond.
  • The study was very small with no healthy control group.
  • ME/CFS was diagnosed using the Canadian Consensus Criteria.
  • Response to treatment was only assessed through questionnaires and monitoring autoantibody levels (AAB). It’s a shame no other measures were used.
  • The protocol for treatment involved five sessions of immunoadsorption over a period of ten days with a maximum of two days in between treatments, with two further IAs  being offered to responding patients who deteriorate again. Furthermore, the researchers plan to treat patients later from this observational trial if they deteriorate again to see if this can lead to longer remissions. This questions the longevity of this treatment, especially if improvements are not sustained.
  • The research team report that this study provides evidence that immunoadsorption can improve physical function and symptoms for a subset of post Covid ME/CFS patients, however, some of the data presented questions this conclusion, for example, fatigue did not improve. The authors claim that fatigue often shows improvements later in the recovery journey, although evidence is needed to show this.

This is an initial observation study, therefore, much more research is needed to confirm the efficacy and safety of immunoadsorption. However, as these results stand, I am not convinced by the findings, especially as improvements do not seem to be sustained.

(N.B. We also reported on the work by this research group after the Charité Fatigue Conference in May 2023, our report can be found here and see presentation 26, page 10.)

ME/CFS Research References

1. Chronic fatigue syndrome in caregivers of children with cerebral palsy and affecting factors

Pasin T, Karatekin BD, Pasin O.

North Clin Istanb. 2023 Sep 22;10(5):642-650. 


Objective: In this study, the frequency of chronic fatigue syndrome (CFS), sleep disturbances, and quality of life levels in mothers of children with cerebral palsy (CP) was compared in relation to the functional status of the child.

Methods: The caregivers were evaluated with the sociodemographic data form, Chalder fatigue scale (ChFS), Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index, and Short Form-12, respectively. In addition, the functional status of the child with CP was evaluated with the gross motor function classification system, manual ability classification system (MACS), communication function classification system, and eating and drinking ability classification system.

Results: According to CDC-1994 criteria, 80.4% of the participating mothers have CFS (n=45). While the mean ChFS and FSS scores of housewives were found to be significantly higher than those of full-time workers (p=0.002; p=0.003, respectively), the mean SF-12 MCS was found to be significantly lower (p=0.007).

The rate of housewives was found to be significantly higher in those diagnosed with CFS (p<0.001). The relationship between independent variables and dependent variables data sets as a result of canonical correlation analysis was obtained as 0.815. While the variable with the highest effect among the independent variables is the MACS variable, the variable with the highest percentage of explanation for the dependent variables is ChFS.

Conclusion: The frequency of CFS is very high in mothers of children with CP, and the most important factors in the presence and severity of CFS are the mother's occupational status and the child's manual skills.

2. People With Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Exhibit Similarly Impaired Vascular Function

Marie Mclaughlin, Nilihan E.M. Sanal-Hayes, Lawrence D. Hayes, Ethan C. Berry, Nicholas F. Sculthorpe.

The American Journal of Medicine, 2023. [Epub ahead of print]


Background: This study aimed to compare flow-mediated dilation values between individuals with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and healthy age-matched controls to assess the potential implications for clinical management and long-term health outcomes.

Methods: A case-case-control approach was employed, and flow-mediated dilation measurements were obtained from 51 participants (17 Long COVID patients, 17 ME/CFS patients, and 17 healthy age-matched controls). Flow-mediated dilation values were analysed using one-way ANOVA for between-group comparisons.

Results: Results revealed significantly impaired endothelial function in both Long COVID and ME/CFS groups compared to healthy age-matched controls as determined by maximum % brachial artery diameter post-occlusion compared to pre-occlusion resting diameter (6.99 ± 4.33% and 6.60 ± 3.48% vs. 11.30 ± 4.44%, respectively, both p < 0.05).

Notably, there was no difference in flow-mediated dilation between Long COVID and ME/CFS groups (p = 0.949), despite significantly longer illness duration in the ME/CFS group (ME/CFS: 16 ± 11.15 years vs. Long COVID: 1.36 ± 0.51 years, p < 0.0001).

Conclusion: The study demonstrates that both Long COVID and ME/CFS patients exhibit similarly impaired endothelial function, indicating potential vascular involvement in the pathogenesis of these post-viral illnesses.

The significant reduction in flow-mediated dilation values suggests an increased cardiovascular risk in these populations, warranting careful monitoring and the development of targeted interventions to improve endothelial function and mitigate long-term health implications.

3. Bioimpedance spectroscopy characterization of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) peripheral blood mononuclear cells

Sara Martinez Rodriguez, Alberto Olmo Fernandez, Daniel Martin Fernandez, Isabel Martin-Garrido.

Biomedical Letters, Volume 9, Issue 2: 121-128.


Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling and chronic disease, importantly related to the current COVID-19 pandemic. Currently, there are no specific laboratory tests to directly diagnose ME/CFS.

In this work, the use of impedance spectroscopy is studied as a potential technique for the diagnosis of ME/CFS. A specific device for the electrical characterization of peripheral blood mononuclear cells was designed and implemented.

Impedance spectroscopy measurements in the range from 1 Hz to 500 MHz were carried out after the osmotic stress of the samples with sodium chloride solution at 1M concentration. The evolution in time after the osmotic stress at two specific frequencies (1.36 kHz and 154 kHz) was analyzed.

The device showed its sensitivity to the presence of cells and the evolution of the osmotic processes. Higher values of impedance (around 15% for both the real and imaginary part) were measured at 1.36 kHz in ME/CFS patients compared to control samples. No significant difference was found between patient samples and control samples at 154 kHz.

Results help to further understand the diagnosis of ME/CFS patients and the relation of their blood samples with bioimpedance measurements.

4. Post-COVID and ME/CFS – Do We Need New Disease Theories?

Schauenburg H.

Z Psychosom Med Psychother. 2023 Oct 13:OA7. [Epub ahead of print.]


Background and Research Question: The SARS-CoV-2 pandemic often resulted in prolonged illness courses. A particular challenge today lies in the clinical presentation resembling that of Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS). 

Method: We review selected literature concerning the psychosocial factors influencing chronic courses characterized primarily by fatigue. Additionally, we explore the neurobiologically grounded theory of “Predictive Coding” as a possible explanatory framework for complex somato- psychic interactions. 

Results: Physical findings only partially account for the dynamics and progression of chronic fatigue syndromes, necessitating more intricate disease models that incorporate aspects of bodily perception. 

Conclusions: Incorporating these newer theories of perception and behavior could provide a more helpful perspective on phenomena such as fatigue, leading to improved therapeutic support measures, all without contributing to premature attributions of “psychological” causes and the associated risk of stigmatization.

5. Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies-An Interim Report

Stein E, Heindrich C, Wittke K, Kedor C, Kim L, Freitag H, Krüger A, Tölle M, Scheibenbogen C.

J Clin Med. 2023 Oct 9;12(19):6428.


There is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS.

We have already conducted two small proof-of-concept studies on IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients. This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective was to assess the improvement in functional ability.

Due to the urgency of finding therapies for post-COVID-Syndrome (PCS), we report here the interim results of the first ten patients, with seven responders defined by an increase of between 10 and 35 points in the Short-Form 36 Physical Function (SF36-PF) at week four after IA.

The results of this observational study will provide the basis for patient selection for a randomised controlled trial (RCT), including sham apheresis, and for an RCT combining IA with B-cell depletion therapy. 

6. Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome from Early Symptoms of COVID-19 Infection

Hua C, Schwabe J, Jason LA, Furst J, Raicu D. 

Psych. 2023; 5(4):1101-1108.


It is still unclear why certain individuals after viral infections continue to have severe symptoms. We investigated if predicting myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) development after contracting COVID-19 is possible by analyzing symptoms from the first two weeks of COVID-19 infection.

Using participant responses to the 54-item DePaul Symptom Questionnaire, we built predictive models based on a random forest algorithm using the participants’ symptoms from the initial weeks of COVID-19 infection to predict if the participants would go on to meet the criteria for ME/CFS approximately 6 months later.

Early symptoms, particularly those assessing post-exertional malaise, did predict the development of ME/CFS, reaching an accuracy of 94.6%. We then investigated a minimal set of eight symptom features that could accurately predict ME/CFS. The feature reduced models reached an accuracy of 93.5%.

Our findings indicated that several IOM diagnostic criteria for ME/CFS occurring during the initial weeks after COVID-19 infection predicted Long COVID and the diagnosis of ME/CFS after 6 months.

7. A systemic review on chronic fatigue syndrome

K. Sreevasumathi, K. T. Naik.

World Journal of Pharmaceutical Science and Research, 2 (5):8-20.


Despite hurting encephalomyelitis/chronic fatigue syndrome (ME/CFS) moving legion individuals worldwide, several clinicians lack the information to suitably diagnose or manage ME/CFS.

Sadly, clinical steering has been scarce, obsolete, or probably harmful. Consequently, up to 91% of patients within the US stay unknown, and people diagnosed typically receive inappropriate treatment. These issues are a unit of accelerating importance as a result of when acute COVID-19, a big proportion of individuals stay sick for several months with associate unhealthiness almost like ME/CFS.

In 2015, the North American nation National Academy of drugs printed new evidence-based clinical diagnostic criteria that are adopted by the North American nation Centers for malady management and interference. moreover, the u. s. and alternative governments furthermore as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral medical care because the treatment of selection for patients with ME/CFS.

Recently, twenty one clinicians specializing in ME/CFS convened to debate best clinical practices for adults full of ME/CFS. This text summarizes their prime recommendations for student and specialist health care suppliers supported recent scientific progress and decades of clinical expertise.

There are a unit several steps that clinicians will want improve the health, function, and quality of lifetime of those with ME/CFS, together with those in whom ME/CFS develops when COVID-19. Patients with a lingering unhealthiness that follows acute COVID-19 United Nations agency don't totally meet criteria for ME/CFS may additionally enjoy these approaches.

8. Sex and disease severity-based analysis of steroid hormones in ME/CFS

Cornelia Pipper, Linda Bliem, Luis León, Daniela Mennickent, Claudia Bodner, et al.

ResearchSquare [Preprint]


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by decreased daily activity and persistent fatigue after physical and/or cognitive exertion. Although ME/CFS affects both sexes, there is a higher preponderance of cases in women. However, endocrinological studies focused on evaluating this sex-related disparity are limited.

In this scenario, the aim of this study was to measure 9 circulating steroid hormones (SHs) divided into mineralocorticoids (aldosterone), glucocorticoids (cortisol, corticosterone, 11-deoxycortisol, cortisone), androgens (androstenedione, testosterone), and progestins (progesterone, 17α-hydroxyprogesterone) in plasma samples from mild/moderate (ME/CFSmm; females, n=20; males, n=8), severely affected patients (ME/CFSsa; females, n=24; males, n=6), and healthy controls (HC, females, n=12; males, n=17) using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).

After correction for multiple testing, we observed that circulating levels of 11-deoxycortisol, 17α hydroxyprogesterone in females, and progesterone in males were significantly different between HC, ME/CFSmm and ME/CFSsa.

Comparing two independent groups, we found that female ME/CFSsa had higher levels of 11-deoxycortisol (vs. HC and ME/CFSmm) and 17α hydroxyprogesterone (vs. HC).

In addition, female ME/CFSmm showed a significant increase in progesterone levels relative to HC. In contrast, we observed that male ME/CFSmm had lower circulating levels of cortisol and corticosterone, while progesterone levels were elevated compared to HC.

In addition to these univariate analyses, our correlational and multivariate approaches identified differential associations between our study groups. Also, using two component partial least squares discriminant analysis (PLS-DA), we were able to discriminate ME/CFS from HC with an accuracy of 0.712 and 0.846 for females and males, respectively.

In conclusion, our findings not only suggest the potential value of including SHs in future studies aimed at improving stratification in ME/CFS, but also provide new perspectives to explore the clinical relevance of these SH-related differences within specific patient subgroups.

9. Case Report: Rapid and partially persistent, improvements of anorexia nervosa and probable myalgic encephalo-myelitis/chronic fatigue syndrome upon metreleptin treatment during two dosing episodes

Jochen Antel, Johannes Hebebrand, Linda Von Piechowski, Cordula Kiewert, Burkhard Stüve, Gertraud Gradl-Dietsch.

Front. Psychiatry, Sec. Adolescent and Young Adult Psychiatry, Volume 14 – 2023.


A comorbidity of anorexia nervosa (AN) and myalgic encephalomyelitis (ME/CSF) is uncommon. A 17-year-old male adolescent with possible onset of ME/CFS after an Epstein Barr Virus infection (EBV) and later onset of AN during a second period of weight loss was twice treated off-label with metreleptin for 15 and 11 days, respectively.

As in previous cases, eating disorder specific cognitions and mood improved. Interestingly, fatigue and post-exertional muscle pain (P-EMP) improved, too. We discuss potential mechanisms. Treatment with metreleptin may prove beneficial in AN and in ME/CSF associated with substantial weight loss.

Long-COVID Research References

  1. Neutrophil extracellular traps and long COVID
  2. First insights into multidisciplinary and multispecialty Long COVID networks – a SWOT analysis from the perspective of ambulatory health care professionals
  3. Stress, anxiety, and depression severity among individuals with no history, previous history, or current history of long COVID
  4. The distinctive immune features of long COVID
  5. Vitamin B12 as an epidrug for regulating peripheral blood biomarkers in long COVID-associated visuoconstructive deficit
  6. The lived experience of long COVID: A qualitative study of mental health, quality of life, and coping
  7. Sociodemographic and Clinical Profile of Long COVID-19 Patients, and Its Correlation with Medical Leave: A Comprehensive Descriptive and Multicenter Study
  8. Long COVID coping and recovery (LCCR): Developing a novel recovery-oriented treatment for veterans with long COVID
  9. Psychophysical therapy and underlying neuroendocrine mechanisms for the rehabilitation of long COVID-19
  10. Gut-brain pathogenesis of post-acute COVID-19 neurocognitive symptoms
  11. Pulmonary embolism in patients in acute COVID-19, long-COVID and post-COVID syndrome
  12. Insomnia and sleep characteristics in post COVID-19 fatigue: A cross-sectional case-controlled study
  13. Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials
  14. Meta-analysis risk factors for long covid-19
  15. Brain fog in long COVID: A glutamatergic hypothesis with astrocyte dysfunction accounting for brain PET glucose hypometabolism
  16. Maximal Oxidative Capacity During Exercise is Associated with Muscle Power Output in Patients with Long coronavirus disease 2019 (COVID-19) Syndrome. A Moderation Analysis
  17. Monitoring the change in the quality of life of patients with post-COVID syndrome by influence on their functional status
  18. Prognosis of patients with long COVID symptoms: a protocol for a longitudinal cohort study at a primary care referred outpatient clinic in Helsinki, Finland
  19. Long COVID: A Chronic Shortage of Blood. Pathophysiology and Treatment Proposal
  20. Cognitive-behavioral therapy for patients with post-COVID-19 condition (CBT-PCC): a feasibility trial
  21. Persistent respiratory symptoms associated with post-covid condition (Long covid) in children: a systematic review and analysis of current gaps and future perspectives

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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