MEA Research Roundup

ME/CFS and Long Covid Research: 10  – 16 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 10  – 16 January 2023 

Research has picked up this week, with five new ME/CFS studies and sixteen new Long Covid studies. 

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

Paper one (1) is a short review article giving an opinion on treatment for ME/CFS and Long Covid. The single author of this review gives a short summary of the key mechanisms they feel are at play within these two conditions. 

The review covers a range of treatments, which could be investigated by the patient, including natural remedies, acupuncture and homeopathy. The importance of a high-quality diet and of moderating sport is also covered, but pacing is not mentioned specifically.  

Interestingly, the use of unregistered medications and next generation anti-inflammatory medicines is also covered, and these focus on resolving the key mechanisms which are included in the introduction. For example, one option covered is sodium dichloroacetate which could be used to reduce the negative effect of the mitochondrial enzyme pyruvate dehydrogenase kinase which in turn affects glucose metabolism, this treatment is proposed as mitochondrial function is known to be affected in ME/CFS. Sodium dichloroacetate could be combined with Meldonium to further increase the benefits to energy production. However, no data is given to prove the effectiveness of these treatments. Less controversially another option covered is intravenous multivitamins, there is some data from an open-label trial to support this recommendation.  

This review is very short, only four pages, including references. Therefore, it is not in depth and how well the different treatments suggested have been researched can be questioned. Due to its length, there is a number of options that have not been covered (e.g.. Chinese medicine which we frequently see studies on). A number of different pharmacological treatments are briefly covered, but there is little or no data to support their use in ME/CFS. It would be nice if some of the suggestions were picked at by other researchers and followed up with clinical trials, but I feel this will be a standalone review only. 

The take-away message is: this review is not well referenced, and is an opinion article only.  

(NB. Please consult your doctor about any change in treatment. The MEA have a variety of leaflets on diet and nutrition, management, and vitamins and supplements.) 

You may also be interested in reading: 

  • Paper three (3) showing the similar symptomatology in ME/CFS and Long Covid, further indicating multisystemic dyshomeostasis in these conditions. However, biomedical studies are needed to prove this. 
  • Paper five (5) which highlights the flaws in the German healthcare guideline which recommends GET and CBT, and opposes the conclusion made by NICE. 

In the Long Covid reference section you may also be interested in Paper one (1) showing the importance of pacing on post-exertional malaise (PEM) in Long Covid. 

ME/CFS Research References and Abstracts  

1. The Role of Immunity and Inflammation in ME/CFS and Post-COVID Syndrome: Implications for Treatment 

Comhaire F. 

MedLife Clinics 2022, Volume 4 (2), Article 1043 


Probably one in seven patients who have experienced acute COVID-19 continue having long-lasting complaints, called post-COVID syndrome or long-COVID, that are similar to those observed in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).  

There are good reasons to believe that common immunological, epigenetic and inflammatory mechanisms are involved in the pathogenesis both diseases.  

To date, various therapeutic approaches have been recommended, but with moderate success. In the present opinion paper, the author weights his clinical experience against data from the literature, and suggests novel approaches.  

In addition to general measures and paramedical approaches, food supplementation with a specific nutraceutical can be completed by oral administration of sodium dichloroacetate and Meldonium to optimize glucose metabolism and mitochondrial energy generation.  

Alternatively, intravenous infusions with magnesium salt and multivitamins can be completed with glutathione, m-tranexamic acid, and cultured stem cells.  

Preliminary results of an open-label, prospective, two-centre trial suggest more than four in five patients benefit from combined oral and infusion therapy with significantly diminished fatigue and improved well-being.  

Monoclonal antibodies in “biologicals”, blocking the effects of cytokines, and “small molecules” with Janus kinase inhibiting activity may offer novel opportunities by focusing on both immunologic and inflammation targets. A pilot trial with, in particular, one of the Janus kinase inhibitors could be considered. 

2. “I Just Want to Feel Safe Going to a Doctor”: Experiences of Female Patients with Chronic Conditions in Australia 

Merone L, Tsey K, Russell D, Nagle C.  

Womens Health Rep (New Rochelle). 2022 Dec 22;3(1):1016-1028.  


Background: The androcentric history of medicine and medical research has led to an ongoing sex and gender gap in health research and education. Sex and gender gaps in research and education may translate into real-life health inequities for women. This study aimed to explore the experiences of female patients with chronic health conditions in the Australian health system, considering existing sex and gender gaps in medicine. 

Methods: This qualitative study used semistructured in-depth interviews with a sample of adult women with chronic conditions in Australia. Thematic analysis was undertaken, guided by Braun and Clarke. Software NVivoX64 assisted in the management of the data. Coding was performed before grouping into subthemes and central themes. To allow for potential researcher biases, the principal researcher engaged in the practice of reflexivity, including the writing of detailed notes during analysis. 

Results: Twenty adult Australian women with chronic conditions were interviewed. Diagnoses were varied and included Ehlers-Danlos syndrome, chronic fatigue syndrome, functional neurological disorder, and inflammatory bowel disease. Four central themes emerged: diagnostic difficulties; spectrum of health care experiences; understanding medical complexity; and coping with symptoms. 

Conclusions: Women with chronic conditions in Australia report pain, fatigue, and suffering that significantly impacts upon their daily lives. There was a shared experience of feeling that the pain and suffering of women was dismissed or not taken seriously. Many women expressed trauma because of their experiences in health care and often this led to a fear of accessing health services. The participants highlighted a need for more knowledge, understanding, and empathy from health care practitioners. 

3. Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis 

Marks DF.  

Biomedicines. 2023; 11(1):180. 


The purpose of this article is to review the evidence of similar symptomatology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of SARS-CoV-2 infection (PASC).  

Reanalysis of data from a study by Jason comparing symptom reports from two groups of ME/CFS and PASC patients shows a notably similar symptomatology.  

Symptom scores of the PASC group and the ME/CFS group correlated 0.902 (p < 0.0001) across items.  

The hypothesis is presented that ME/CFS and PASC are caused by a chronic state of multisystemic disequilibrium including endocrinological, immunological, and/or metabolic changes.  

The hypothesis holds that a changed set point persistently pushes the organism towards a pathological dysfunctional state which fails to reset.  

To use an analogy of a thermostat, if the ‘off switch’ of a thermostat intermittently stops working, for periods the house would become warmer and warmer without limit.  

The hypothesis draws on recent investigations of the Central Homeostasis Network showing multiple interconnections between the autonomic system, central nervous system, and brain stem.  

The hypothesis helps to explain the shared symptomatology of ME/CFS and PASC and the unpredictable, intermittent, and fluctuating pattern of symptoms of ME/CFS and PASC. The current theoretical approach remains speculative and requires in-depth investigation before any definite conclusions can be drawn. 

4. Autonomic Nervous System Regulation Effects of Epipharyngeal Abrasive Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Associated With Chronic Epipharyngitis 

Hirobumi I.  

Cureus 15(1): e33777.  


Objective: To evaluate the autonomic nerve stimulation effect of epipharyngeal abrasive therapy (EAT) on myalgic encephalomyelitis/chronic fatigue syndrome (CFS) associated with chronic epipharyngitis. Heart rate variability analysis was performed. The study was conducted by analyzing heart rate variability. 

Subjects and methods: A total of 29 patients with chronic epipharyngitis who underwent EAT from July 2017 to April 2018 were classified into two groups: 11 patients in the CFS group and 18 patients in the control group without CFS.  

The patients were classified as phase 1 during bed rest, phase 2 during nasal endoscopy, phase 3 during nasal abrasion, and phase 4 during oral abrasion.  

Electrocardiographic recordings were made, and autonomic function was compared and evaluated by measuring heart rate, coefficient of variation on R-R interval (CVRR), coefficient of component variance high frequency (ccvHF), and low frequency/ccvHF ratio (L/H) for each of the four phases. The Shapiro-Wilk test was performed to confirm the normality of the two groups, and the parametric test was selected.  

A repeated measures analysis of variance was performed to assess changes over time between the four events in the two groups. Multiple comparisons were corrected by the Bonferroni method. Comparisons between resting data and three events within each group were performed by paired t-test. 

Results: The CFS group had an increased baseline heart rate compared to the control group, and the CFS group had a greater increase in parasympathetic activity and a decrease in heart rate with nasal abrasion. Oral abrasion elicited a pharyngeal reflex and increased heart rate and both sympathetic and parasympathetic activity. 

Conclusion: The CFS group was in a state of dysautonomia due to autonomic overstimulation, with an elevated baseline heart rate. The CFS group was considered to be in a state of impaired autonomic homeostasis, with an increased likelihood that overstimulation would induce a pathological vagal reflex and the Reilly phenomenon would develop.  

The direct effects of EAT on the autonomic nervous system were considered to be vagus nerve stimulation and the regulation of autonomic function by opposing stimulation input to sympathetic and parasympathetic nerves. As an indirect effect, bleeding from the epipharyngeal mucosa due to abrasion was thought to restore the function of the cerebral venous and lymphatic excretory systems and the autonomic nerve center. 

5. The Draft Report by the Institute for Quality and Efficiency in Healthcare Does Not Provide Any Evidence That Graded Exercise Therapy and Cognitive Behavioral Therapy Are Safe and Effective Treatments for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 

Vink M, Vink-Niese A. 

Diseases. 2023; 11(1):11. 


The German Institute for Quality and Efficiency in Healthcare (IQWiG) recently published its draft report to the government about myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The IQWiG concluded that graded exercise therapy (GET) and cognitive behavioral therapy (CBT) should be recommended in the treatment for mild and moderate ME/CFS based on two CBT and two GET studies.  

In this article, we reviewed the evidence used by IQWiG to support their claims, because their conclusion is diametrically opposed to the conclusion by the British National Institute for Health and Care Excellence (NICE) in its recently updated ME/CFS guidelines.  

Our analysis shows that the trials IQWiG used in support suffered from serious flaws, which included badly designed control groups; relying on subjective primary outcomes in non-blinded studies; alliance and response shift bias, including patients in their trials who did not have the disease under investigation, selective reporting, making extensive endpoint changes and low to very low adherence of treatments.  

Our analysis also shows that the report itself used one CBT and one GET study that both examined a different treatment. The report also used a definition of CBT that does not reflect the way it is being used in ME/CFS or was tested in the studies.  

The report noted that one study used a wrong definition of post-exertional malaise (PEM), the main characteristic of the disease, according to the report. Yet, it ignored the consequence of this, that less than the required minimum percentage of patients had the disease under investigation in that study. It also ignored the absence of improvement on most of the subjective outcomes, as well as the fact that the IQWiG methods handbook states that one should use objective outcomes and not rely on subjective outcomes in non-blinded studies.  

The report concluded that both treatments did not lead to objective improvement in the six-minute walk test but then ignored that. The report did not analyze the other objective outcomes of the studies (step test and occupational and benefits status), which showed a null effect.  

Finally, the report states that the studies do not report on safety yet assumes that the treatments are safe based on a tendency towards small subjective improvements in fatigue and physical functioning, even though the adherence to the treatments was (very) low and the studies included many patients who did not have the disease under investigation and, consequently, did not suffer from exertion intolerance contrary to ME/CFS patients.  

At the same time, it ignored and downplayed all the evidence that both treatments are not safe, even when the evidence was produced by a British university.  

In conclusion, the studies used by the report do not provide any evidence that CBT and GET are safe and effective. Consequently, the report and the studies do not provide any support for the recommendation to use CBT and GET for ME/CFS or long COVID, which, in many cases, is the same or resembles ME/CFS, after an infection with SARS-CoV-2. 

Long-COVID Research References  

  1. Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome 
  1. SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19 
  1. Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective 
  1. Long COVID and mental health correlates: a new chronic condition fits existing patterns 
  1. Long COVID in the Older Adult and Vitamin D 
  1. Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study 
  1. Long COVID Symptomatology and Associated Factors in Primary Care Patients: The EPICOVID-AP21 Study 
  1. Long COVID: major findings, mechanisms and recommendations 
  1. Impacts of delta and omicron variants on inactivated SARS-CoV-2 vaccine-induced T cell responses in patients with autoimmune diseases and healthy controls 
  1. A Systematic Review of Trials Currently Investigating Therapeutic Modalities for Post-Acute COVID-19 Syndrome and Registered on World Health Organization International Clinical Trials Platform 
  1. Towards evidence-based and inclusive models of peer support for long covid: A hermeneutic systematic review 
  1. Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study 
  1. Long COVID: Is There a Role for Antidepressants? 
  1. Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers” 
  1. Can Baseline IL-6 Levels Predict Long COVID in Subjects Hospitalized for SARS-CoV-2 Disease? 
  1. Epidemiology, symptomatology, and risk factors for long COVID symptoms: Multi-centre study 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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