ME Association Index Of Published Research

ME/CFS and Long Covid Research: 19 – 25 September 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 six new ME/CFS studies and twenty-three new Long Covid studies this week.

Not much caught our eyes this week, with very limited biomedical studies. We have highlighted one of the ME/CFS studies in more detail below:

Paper five (5) is a preprint (meaning it has not been peer-reviewed and the science verified) which looks into long gene sequencing to help explain severe fatigue disorders including ME/CFS.

DNA sequencing is the process of reading some or all of the DNA from organisms. Studies often use short gene sequencing techniques due to how long the human genome is, meaning it cannot be sequenced in a continuous string so is broken into fragments. Long gene sequencing allows much larger sections of the genome to be sequenced, DNA can be sequenced in real time. This is sometimes referred to as third generation sequencers. This has benefits in genome reconstruction and analysis, which is thought to be beneficial in the diagnosis of diseases. (More on the different sequencing techniques can be found here.)

This study is a proof of concept study, as the investigation of this technique was based only on one patient whose severe mental and physical fatigue started after a viral infection at age 16, now 42 years old. Interestingly, the diagnosis of ME/CFS was removed as it was proving a barrier to accessing treatments for other conditions. There was also a family history of fatigue, the study states several times that ME/CFS is heritable, however, we are not aware of any strong evidence which shows this.

The sample size is definitely disappointing as this technique has the potential to provide so much more insight. In this patient the upregulation of the gene region AKR1C2 combined with partial loss of AKR1C1 may explain the severe fatigue experienced, this provides evidence for hormone dysfunction. This could, therefore, be a potential biomarker to target.

As it stands, this study provides a complex look into gene sequencing, and some interesting take away points. Simply this research shows:

  • The power of long gene sequencing techniques in characterising gene regions which are difficult to access through short reads/typical techniques.
  • The technique has the potential to provide a molecular diagnosis for genetic conditions, revealing underlying causes of conditions of unknown aetiology.
  • The technique is currently costly, but there is a hope as technologies improve costs will fall and algorithms will improve making long read sequencing more widely available.
  • This study shows that more large genetic studies are needed, such as DecodeME which is the world’s largest ME/CFS study (although using different techniques).

You may also be interested in reading this week:

  • Paper one (1) which is a published report from the Charité Fatigue Centre conference which took place in May 2023. We have also previously reported on a selection of the presentations which can be found here.
  • Paper three (3) is a disappointing paper on guidance for health professionals in Norway. Sadly, the MEA is cited as a source of misinformation in this study, you can read the MEA’s response to this on our website.

ME/CFS Research References

1. Understanding, diagnosing, and treating Myalgic encephalomyelitis/chronic fatigue syndrome – State of the art: Report of the 2nd international meeting at the Charité fatigue center

Steiner, Fehrer, Hoheisel, Schoening, Aschenbrenner, Babel, Bellmann-Strobl, Finke, Fluge, Froehlich, Goebel, Grande, Haas, Hohberger, Jason, Komaroff, Lacerda, Liebl, Maier, Mella, Nacul, Paul, Prusty, Puta, Riemekasten, Ries, Rowe, Sawitzki, Shoenfeld, Schultze, Seifert, Sepúlveda, Sotzny, Stein, Stingl, Ufer, Veauthier, Westermeier, Wirth, Wolfarth, Zalewski, Behrends, Scheibenbogen.

Autoimmunity Reviews: 103452. [In press, Journal pre-proof]


Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating disease affecting millions of people worldwide. Due to the 2019 pandemic of coronavirus disease (COVID-19), we are facing a significant increase of ME/CFS prevalence.

On May 11th to 12th, 2023, the second international ME/CFS conference of the Charité Fatigue Center was held in Berlin, Germany, focusing on pathomechanisms, diagnosis, and treatment. During the two-day conference, more than 100 researchers from various research fields met on-site and over 700 attendees participated online to discuss the state of the art and novel findings in this field.

Key topics from the conference included: the role of the immune system, dysfunction of endothelial and autonomic nervous system, and viral reactivation. Furthermore, there were presentations on innovative diagnostic measures and assessments for this complex disease, cutting-edge treatment approaches, and clinical studies.

Despite the increased public attention due to the COVID-19 pandemic, the subsequent rise of Long COVID-19 cases, and the rise of funding opportunities to unravel the pathomechanisms underlying ME/CFS, this severe disease remains highly underresearched. Future adequately funded research efforts are needed to further explore the disease etiology and to identify diagnostic markers and targeted therapies.

2. Association Between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Cardiovascular Disease

Mawulorm KI Denu, Ritika Revoori, Cherita Eghan, Fredrick Larbi Kwapong, Andrew Hillman, Cornelius A Normeshie, Kofi Poku Berko, Emily L. Aidoo, Maame Araba E Buadu.

ResearchSquare [Preprint]


Background: Chronic Fatigue Syndrome or Myalgic Encephalomyelitis (CFS/ME) is a medical condition characterized by severe and prolonged fatigue that is not relieved by rest or attributed to any underlying medical or psychological condition. Individuals with CFS/ME are considered to have an increased risk of a wide range of comorbid conditions, including cardiovascular disease (CVD). The association between CFS/ME and CVD is not fully understood.

Objective: To determine the prevalence of CFS/ME in a sample population and examine its association with CVD.

Methods: Data was analyzed from the 2021 National Health Interview Survey (NHIS). Information on sociodemographic factors, CVD risk factors, and history of CFS/ME and CVD were collected. Multivariate logistic regression model was used to determine the association between CFS/ME and CVD, adjusting for traditional CVD risk factors (age, sex, race, hypertension, diabetes, dyslipidemia, smoking, and body mass index (BMI).

Results: Median age of participants was 53 years, and majority of participants were female (53.9%). Prevalence of CFS/ME was 1.4%. A history of CFS/ME was significantly associated with CVD (aOR: 3.13, 95%CI: 2.37, 4.15, p-value:<0.001) after adjusting for traditional CVD risk factors.

Conclusion: A history of CFS/ME was independently associated with CVD after adjusting for traditional CVD risk factors. Patients with CFS/ME need close evaluation for CVD. Further studies are needed to better understand the relationship between CFS/ME and CVD.

3. Chronic fatigue syndromes: real illnesses that people can recover from

Oslo Chronic Fatigue Consortium; Alme TN, Andreasson A, Asprusten TT, Bakken AK, Beadsworth MB, Boye B, Brodal PA, Brodwall EM, Brurberg KG, Bugge I, Chalder T, Due R, Eriksen HR, Fink PK, Flottorp SA, Fors EA, Jensen BF, Fundingsrud HP, Garner P, Havdal LB, Helgeland H, Jacobsen HB, Johnson GE, Jonsjö M, Knoop H, Landmark L, Launes G, Lekander M, Linnros H, Lindsäter E, Liira H, Linnestad L, Loge JH, Lyby PS, Malik S, Malt UF, Moe T, Norlin AK, Pedersen M, Pignatiello SE, Rask CU, Reme SE, Roksund G, Sainio M, Sharpe M, Thorkildsen RF, van Roy B, Vandvik PO, Vogt H, Wyller HB, Wyller VBB.

Scand J Prim Health Care. 2023 Sep 23:1-5.


The ‘Oslo Chronic Fatigue Consortium' consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients.

Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process.

Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided.

We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation. Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities.

Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.

4. Prevalence of Fibromyalgia and Chronic Fatigue Syndrome among Individuals with Irritable Bowel Syndrome: An Analysis of United States National Inpatient Sample Database

Tarar ZI, Farooq U, Nawaz A, Gandhi M, Ghouri YA, Bhatt A, Cash BD.

Biomedicines. 2023; 11(10):2594.


Background and Aim: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with other somatic disorders. We studied the prevalence and predictors of fibromyalgia and chronic fatigue syndrome (CFS) in IBS patients. 

Methods: We used the National Inpatient Sample and included hospitalization of individuals with IBS, using ICD-10 codes, from 2016–2019. The prevalence and predictors of fibromyalgia and CFS in IBS patients were studied. Univariate and multivariate patient- and hospital-level regression models were used to calculate the adjusted odds of fibromyalgia and CFS in the IBS patient population. 

Results: Of 1,256,325 patients with an ICD-10 code of IBS included in the study, 10.73% (134,890) also had ICD-10 codes for fibromyalgia and 0.42% (5220) for CFS. The prevalence of fibromyalgia and CFS was significantly higher in IBS patients (adjusted odds ratio (AOR) 5.33, 95% confidence interval (CI) 5.24–5.41, p < 0.001, and AOR 5.40, 95% CI 5.04–5.78, p < 0.001, respectively) compared to the general adult population without IBS.

IBS-diarrhea, IBS-constipation, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS. Increasing age (AOR 1.02, 95% CI 1.01–1.04, p 0.003; AOR 1.02, 95% CI 1.01–1.03, p 0.001), female gender (AOR 11.2, 95% CI 11.1–11.4, p < 0.001; AOR 1.86, 95% CI 1.78–1.93, p < 0.001) and white race (AOR 2.04, 95% CI 1.95–2.12, p < 0.001; AOR 1.69, 95% CI 1.34–2.13, p < 0.001) were independent predictors of increased odds of fibromyalgia and CFS, respectively. 

Conclusions: It appears that IBS is associated with an increased prevalence of somatic disorders such as fibromyalgia and CFS.

5. Healthcare system barriers impacting the care of Canadians with myalgic encephalomyelitis: a scoping review

Said Hussein, Lauren Eiriksson, Maureen MacQuarrie, Scot Merriam, Maria Dalton, Eleanor Stein, Rosie Twomey.

medRxiv [Preprint]


Background: Myalgic encephalomyelitis (ME, also known as chronic fatigue syndrome or ME/CFS) is a debilitating, complex, multi-system illness. Developing a comprehensive understanding of the multiple and interconnected barriers to optimal care will help advance strategies and care models to improve quality of life for people living with ME in Canada.

Objectives: To: (1) identify and systematically map the available evidence; (2) investigate the design and conduct of research; (3) identify and categorize key characteristics; and (4) identify and analyze knowledge gaps related to healthcare system barriers for people living with ME in Canada.

Methods: The protocol was preregistered in July 2022. Peer-reviewed and grey literature was searched, and patient partners retrieved additional records. Eligible records were Canadian, included people with ME/CFS and included data or synthesis relevant to healthcare system barriers.

Results: In total, 1821 records were identified, 406 were reviewed in full, and 21 were included. Healthcare system barriers arose from an underlying lack of consensus and research on ME and ME care; the impact of long-standing stigma, disbelief, and sexism; inadequate or inconsistent healthcare provider education and training on ME; and the heterogeneity of care coordinated by family physicians.

Conclusions: People living with ME in Canada face significant barriers to care, though this has received relatively limited attention. This synthesis, which points to several areas for future research, can be used as a starting point for researchers, healthcare providers and decision-makers who are new to the area or encountering ME more frequently due to the COVID-19 pandemic.

5. Long read sequencing characterises a novel structural variant, revealing underactive AKR1C1 with overactive AKR1C2 as a possible cause of unexplained severe fatigue

Julia Oakley, Martin Hill, Adam Giess, Mélanie Tanguy, Greg Elgar.

ResearchSquare [Preprint]


Background: Causative genetic variants cannot yet be found for many disorders with a clear heritable component, including chronic fatigue disorders like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These conditions may involve genes in difficult-to-align genomic regions that are refractory to short read approaches. Structural variants in these regions can be particularly hard to detect or define with short reads, yet may account for a significant number of cases. Long read sequencing can overcome these difficulties but so far little data is available regarding the specific analytical challenges inherent in such regions, which need to be taken into account to ensure that variants are correctly identified.

Research into chronic fatigue disorders faces the additional challenge that the heterogeneous patient population likely encompasses multiple aetiologies with overlapping symptoms, rather than a single disease entity, such that each individual abnormality may lack statistical significance within a larger sample. Better delineation of patient subgroups is needed to target research and treatment.

Methods: We use nanopore sequencing in a case of unexplained severe fatigue to identify and fully characterise a large inversion in a highly homologous region spanning the AKR1C gene locus, which was indicated but could not be resolved by short-read sequencing. We then use GC-MS/MS serum steroid analysis to investigate the functional consequences.

Results: Several commonly used bioinformatics tools are confounded by the homology but a combined approach including visual inspection allows the variant to be accurately resolved. The DNA inversion appears to increase the expression of AKR1C2 while limiting AKR1C1 activity, resulting in a relative increase of inhibitory neurosteroids and impaired progesterone metabolism.

Conclusions: This study provides an example of how long read sequencing can improve diagnostic yield in research and clinical care, and highlights some of the analytical challenges presented by regions containing tandem arrays of genes. It also proposes a novel gene associated with a specific disease aetiology that may be an underlying cause of complex chronic fatigue and possibly other conditions too. It reveals biomarkers that could be assessed in a larger cohort, potentially identifying a subset of patients who might respond to treatments suggested by the aetiology.

6. New government delivery plan to support children with myalgic encephalomyelitis

Dorothy Lepkowska.

British Journal of Child Health, Vol. 4, No. 4.


The new plan, which is currently out for consultation, calls for schools to be flexible to help support children and young people with conditions such as myalgic encephalomyelitis or chronic fatigue syndrome to help them access education. Dorothy Lepkowska explains.

Long-COVID Research References

  1. Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort study
  2. Proximal immune-epithelial progenitor interactions drive chronic tissue sequelae post COVID-19
  3. Post–COVID-19 Condition in Children
  4. Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care
  5. Immune Adsorption for the Treatment of Fatigue-Dominant Long-/Post-COVID Syndrome: A Series of Cases With Standardized Individual Experimental Therapy
  6. Clinical Rationale for Dietary Lutein Supplementation in Post COVID-19 and mRNA Vaccine Injury Syndromes
  7. Effects of six-month creatine supplementation on patient- and clinician-reported outcomes, and tissue creatine levels in patients with post-COVID-19 fatigue syndrome
  8. Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts
  9. Impact of extended-course oral nirmatrelvir/ritonavir (Paxlovid) in established Long COVID: Case series and research considerations
  10. Paxlovid as a potential treatment for long COVID
  11. Long Term Effects of COVID-19 in Adolescents Exploring the Pathophysiology and Psychosocial Factors of Long COVID
  12. The importance of patient-partnered research in addressing long COVID: Takeaways for biomedical research study design from the RECOVER Initiative's Mechanistic Pathways taskforce
  13. Autonomic dysregulation in long-term patients suffering from Post-COVID-19 Syndrome assessed by heart rate variability
  14. Long COVID quality of life and healthcare experiences in the UK: a mixed method online survey
  15. Proximal immune-epithelial progenitor interactions drive chronic tissue sequelae post COVID-19
  16. Living with Long COVID: A Longitudinal Interview Study of Individuals’ Communicative Resilience Through the “Long Haul”
  17. Post-COVID-19 epigenetic signatures
  18. Prevalence of musculoskeletal pain as a long-covid symptom after hospitalisation in covid-19 survivors
  19. Long-Term cognitive dysfunction after the COVID-19 pandemic: a narrative review
  20. Distinguishing features of Long COVID identified through immune profiling
  21. How methodological pitfalls have created widespread misunderstanding about long COVID
  22. What Role Does Microthrombosis Play in Long COVID?

Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit- COVID study

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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