Source: Cai W, Haddad M, Haddad R, Kesten I, Hoffman T, Laan R, Westfall S, Defaye M, Abdullah NS, Wong C, Brown N, Tansley S, Lister KC, Hooshmandi M, Wang F, Lorenzo LE, Hovhannisyan V, Ho-Tieng D, Kumar V, Sharif B, Thurairajah B, Fan J, Sahar T, Clayton C, Wu N, Zhang J, Bar-Yoseph H, Pitashny M, Krock E, Mogil JS, Prager-Khoutorsky M, Séguéla P, Altier C, King IL, De Koninck Y, Brereton NJB, Gonzalez E, Shir Y, Minerbi A, Khoutorsky A. The gut microbiota promotes pain in fibromyalgia. Neuron. 2025 Apr 18:S0896-6273(25)00252-1. doi: 10.1016/j.neuron.2025.03.032. Epub ahead of print. PMID: 40280127. https://www.cell.com/neuron/fulltext/S0896-6273(25)00252-1 (Full text)
Health-related quality of life in people with ME and Long Covid: A conversation with Breanna Weigel, Griffith University, Australia
By Dylan Murphy
In March 2024 the UN Disabilities Committee issued a damning report which stated that disabled people in the UK faced systemic violations of their human rights ranging from cuts to benefits to the lack of housing for disabled people. Fast forward to late February 2025 and the UN Economic and Cultural Committee issued a report on the UK which criticized the Labour government for its failures to reduce poverty and social inequality. Since then our government in its infinite wisdom has decided to slash £7 billion from disability benefits and is removing free bus passes from hundreds of thousands of disabled people on PIP.
On the ME front our government has engaged in endless gas lighting postponing the Department of Health care plan for ME several times. It claims that the care plan for ME will be published sometime in June just when it is due to announce major cuts to public spending which makes it very unlikely that it will put any resources into funding this plan.
In 2017 I put in a freedom of information request to the DWP which revealed that a third of pwME applying for PIP were having their applications turned down. The DWP is of course completely ignorant of the heavy disease burden of ME on those suffering with this wretched illness. It chooses to ignore the wealth of scientific evidence revealing the low quality of life outcomes for pwME.
In light of the above developments I came across a recent research paper, Health-related quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: A systematic review, by a group of scientists from the National Centre for Neuroimmunology and Emerging Diseases (NCNED) at Griffith University, Australia.
One of the co-authors of the above paper, Breanna Weigel, took time out from her busy schedule to talk to me about this important piece of research which may be of value to those pwME navigating the treacherous waters which are our current benefits system. It was such a pleasure to talk to a passionate young scientist who is so committed to the field of ME/Long Covid research. Breanna told me, “ It is a privilege to share these findings with the ME and Long COVID community, who have had an immeasurable impact on my growth as a researcher and my passion for making a difference for people who live with these chronic illness.’’
Breanna Weigel has five years’ experience working in the field of ME/CFS and Long COVID research at the National Centre for Neuroimmunology and Emerging Diseases (NCNED), Griffith University, Gold Coast, Australia. This month, Breanna will be submitting her PhD thesis, titled “Living with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID in Australia: An examination of illness experiences and healthcare policy”.
DM: How did you get involved in the field of ME research?
BW: Chronic illness has been an important part of my life and an area that I have wanted to work in for a long time. My Mum has lived with a chronic illness that has affected her life every day for the last 23 years. Seeing the extensive impacts that this had on my Mum, I was motivated to pursue a career that enabled me to contribute to helping people with chronic illness. I also developed a chronic illness four years ago, which considerably disrupted my life. However, my own lived experiences have provided me with additional insight that has informed my approach to research.
My involvement in ME research commenced in 2019 during my search for a supervisor for my Honours project. As I had a strong interest in public health and epidemiology, my program advisor shared with me the public health research that was being conducted at the National Centre for Neuroimmunology and Emerging Diseases (NCNED) and put me in contact with Prof Sonya Marshall-Gradisnik. It was then that I was introduced to the world of ME research.
I have continued to work with the NCNED over the last five years and I am presently finalising my PhD thesis, which highlights the lived experiences of people with ME and people with Post COVID-19 Condition (PCC). Throughout my early research career, I have had the invaluable opportunity to work directly with people who live with these conditions. Hearing their stories and experiences of living with ME or PCC has strengthened my motivation to make a difference for people who live with chronic illnesses that affect so many aspects of life.
DM: In the paper you co-authored, “Health-related quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: A systematic review”, you make the following observation: “people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) are often precluded from accessing necessary disability and social support services. These unmet care needs exacerbate the existing illness burdens experienced by pwME/CFS and pwPCC.’’
This is a very timely and astute observation.
In October 2023 the Department of Health UK held a public consultation regarding its plans to improve the quality of life for people with ME, which admitted that people with ME face many difficulties accessing disability and social care services. Now we face huge cuts to disability benefits such as Personal Independence Payment (PIP), which many people with ME claim to help them with the extra costs of being disabled. Due to the fluctuating nature of the illness many people with ME have problems claiming disability benefits and accessing social care services.
Bearing this in mind can you explain the purpose of your systematic review?
BW: Unfortunately, many people with ME and people with PCC face similar barriers to receiving such necessary support in Australia. Based on results in my Honours and PhD research, approximately half of the people with ME who participated in these studies and were unable to work due to their illness were not receiving income support through the Disability Support Pension (DSP), which is our federally funded income assistance program here in Australia.
A primary barrier to accessing this necessary support for Australians who live with ME or PCC is the lack of recognition for these illnesses as real, physical disabilities in healthcare policy. The purpose of our recently published systematic review was, therefore, to elucidate that the profound impacts of ME and PCC on the health and functioning of people who live with these conditions warrant access to care and support services, such as the DSP.
The systematic review method enabled all relevant studies published worldwide to be included in the analysis. By examining all the existing relevant literature, this systematic review not only provided evidence that ME and PCC are associated with significantly lower quality of life when compared with healthy people, but also indicated that these findings are consistent across studies, countries and time.
DM: Sadly, pwME over many years have suffered from a dismissive and discriminatory attitude from many health professionals and media outlets with their illness being dismissed as psychosomatic in nature. Here in the UK, we still have some of the royal medical colleges maintaining that psychological therapies are an appropriate treatment for pwME. Many people with Long COVID are facing similar negative attitudes towards their illness. Based on the extensive research which you carried out for your systematic review, how would you characterize ME and Long COVID: Are they physical or psychological illnesses?
BW: The findings of our recent systematic review reiterate that ME and PCC are real, physical illnesses that are not psychogenic in nature. I use the term, “PCC”, here as our systematic review specifically examined publications documenting quality of life among people with persistent COVID-19-related symptoms for at least three months, which is consistent with the World Health Organization’s definition of “Post COVID-19 Condition” (PCC).
Importantly, the illness impact trends observed across the studies analyzed in our systematic review highlight that physical health and the ability to complete daily activities are consistently the most substantially impacted components of quality of life among people with ME and people with PCC. In addition, mental health was consistently the least impacted component of quality of life among these two cohorts. These findings affirm that, whilst living with an invisible and incurable chronic illness can have significant mental health repercussions, these impacts are secondary to and not causative of ME or PCC.
This conclusion is supported by the extensive literature documenting disruptions to cellular functioning among people with ME and people with PCC. This includes the world-first research from the NCNED. Laboratory-based studies from our Centre have consistently identified impaired TRPM3 calcium ion channel function among people * with ME and people with PCC, in which these impairments are absent in healthy people. * see footnote for explanation of this term.
DM: People with ME suffer from a multitude of symptoms which have a very debilitating and disabling impact on their lives. Can you explain the disabling impact of the illness on people with ME and its long-term impact on them? Do people with Long COVID suffer from the same issues?
BW: Our systematic review, for the first time, provides consistent evidence of the shared widespread impact of ME and PCC on the health and well being of people with these conditions. Overall health, as well as all individual aspects of health and functioning, are considerably poorer among pwME and pwPCC when compared with healthy people.
In conjunction with the results of two other studies that contribute to my PhD project (which were published in 2024 [1, 2]) and the NCNED’s laboratory findings [3, 4], the illness impact patterns observed in our systematic review indicate that the collection of post-COVID-19 sequelae (an after effect of a disease, condition, or injury) includes an illness presentation that is highly reminiscent of ME.
Combined with the post-viral nature of a considerable proportion of ME cases, this suggests that, after an episode of COVID-19, some people may experience the typical illness trajectory of people with ME. Hence, people who experience ME-like illness after COVID-19 may be at risk of long-term, complex chronic illness associated with widespread and debilitating symptoms, profound limitations on their ability to participate in daily, work and social life, and high healthcare needs.
DM: During the discussion section of your paper, you observe that pwME and people with Long COVID suffer from a comparable, profound level of disability. You note that “the illness presentation of ME/CFS and PCC poses a considerable barrier to completing physical tasks associated with daily living, …’’ Can you please explain this observation with examples from your research?
BW: The ability to participate in typical daily activities was consistently one of the most impacted components of health and functioning across the studies captured in our systematic review. In the context of the patient-reported outcome measures that were used to collect data in these studies, this refers to the ability to complete work both around the home and in relation to employment or study.
Such patient-reported outcome measures used by the studies included in our systematic review (and used in our studies at the NCNED) quantify quality of life and functioning across a range of scales. These include scales that consider overall health, as well as collections of more specific scales that focus on individual aspects of health. In terms of overall health, our research indicates that most people with ME/CFS and people with PCC have a functional status between 30% and 50% of total functioning. This is significantly lower than the level of functioning of healthy people, who typically return a score of (or close to) 100%.
Overall health status scores between 30% and 50% represent a considerable impact on the ability to complete daily activities, such as only being able to complete a limited number of tasks (like housework or grocery shopping) per day with adequate rest periods. However, people experiencing severe illness can return overall health status scores of 20% or 10%. People who return these considerably low scores may be mostly bed bound and unable to shower or eat independently.
The consistent finding that people with ME and people with PCC have a profoundly impaired ability to perform typical daily activities (including being able to continue employment) in our systematic review is critical in relation to guiding care and support access. As these impairments were repeatedly observed through the collection of data by validated and standardised patient-reported outcome measures, this provides evidence that ME and PCC are real, disabling conditions and must be considered eligible for care and support services, such as income assistance.”
DM: Your study is the first systematic review to capture and compare quality of life metrics for both pwME and people suffering from Long COVID. In your paper, you state “The present systematic review therefore serves to elucidate the pervasive impacts of ME/CFS and PCC on people who live with these conditions to inform and guide healthcare policy reform, as well as future research.” What recommendations would you suggest to public health agencies and governments to help pwME and Long COVID have a better quality of life?
BW: The co-production of healthcare policies and services with ME and PCC consumers will be an essential step in improving quality of life for people who live with these conditions. Importantly, care accessibility must be increased for these cohorts and the processes of accessing care must accommodate for the functional limitations of people who live with ME or PCC.
DM: I had the opportunity to further discuss the role of consumers’ lived illness experiences in shaping healthcare policy in my recent collaboration with the Deeble Institute for Health Policy Research, Australian Healthcare and Hospitals Association, which can be accessed via this link: https://doi.org/10.25916/b246-r560
BW: If anyone has any questions after reading the interview or would like to discuss our research in general, they are more than welcome to contact us at ncned@griffith.edu.au
References:
1. Weigel B, Eaton-Fitch N, Thapaliya K, & Marshall-Gradisnik SM. Illness presentation and quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: A pilot Australian cross-sectional study. Qual Life Res. 2024,33(9):2489–507. doi: 10.1007/s11136-024-03710-3.
2. Weigel B, Eaton-Fitch N, Thapaliya K, & Marshall-Gradisnik SM. A pilot cross-sectional investigation of symptom clusters and associations with patient-reported outcomes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition. Qual Life Res. 2024,33(12):3229–43. doi: 10.1007/s11136-024-03794-x.
3. Martini Sasso E, Muraki K, Eaton-Fitch N, Smith P, Lesslar OL, Deed G, et al. Transient receptor potential melastatin 3 dysfunction in Post COVID-19 Condition and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. Mol Med. 2022,28(1):98. doi: 10.1186/s10020-022-00528-y.
4. Martini Sasso E, Muraki K, Eaton-Fitch N, Smith P, Jeremijenko A, Griffin P, et al. Investigation into the restoration of TRPM3 ion channel activity in Post-COVID-19 Condition: A potential pharmacotherapeutic target. Front Immunol. 2024,15:1264702. doi: 10.3389/fimmu.2024.1264702.
Glossary
* What is TRPM3? Imagine TRPM3 as a tiny “gate” on the surface of cells. This gate specializes in allowing calcium ions (charged particles) to flow into the cell when triggered. Calcium acts like a messenger, telling the cell to perform specific tasks.
How Does It Work?
Triggers: The TRPM3 gate opens in response to certain signals, such as heat (like a body temperature rise) or specific molecules (like those released when you’re injured or when blood sugar is high). – Calcium’s Role: Once the gate opens, calcium rushes in, acting like a text message that alerts the cell to take action. This could mean sending a pain signal, releasing hormones, or adjusting to temperature changes.
1. Calcium Signaling & Cellular Stress: What’s Happening?
TRPM3 allows calcium to enter cells, which is critical for communication between nerves, muscles, and the immune system. In ME/CFS, abnormal calcium flow might disrupt this communication.
Impact: Too much calcium in cells (due to overactive TRPM3) could cause “cellular stress,” damaging mitochondria (the cell’s energy factories) or overstimulating nerves. This might explain the fatigue, muscle weakness, and “brain fog” seen in ME/CFS.
2. Pain Sensitivity & Nervous System Overdrive – What’s Happening?
TRPM3 helps nerves detect pain and temperature. If it’s hypersensitive, it might send constant “false alarms” to the brain.
Impact: This could contribute to chronic pain, allodynia (pain from light touch), or temperature intolerance (feeling too hot/cold) common in ME/CFS. It might also worsen “sensory overload,” where lights, sounds, or movement feel overwhelming.
3. Immune System & Inflammation – What’s Happening?
TRPM3 is activated by inflammatory molecules. In ME/CFS, chronic inflammation or immune dysfunction (e.g., after infections like Epstein-Barr virus) might keep TRPM3 stuck in the “on” position.
Impact: This could lead to a vicious cycle: inflammation → TRPM3 overactivity → more inflammation → worsened symptoms. Studies show ME/CFS patients often have abnormal immune cells (like natural killer cells), and TRPM3 defects in these cells might impair their ability to fight infections.
4. Energy Metabolism & Crashes – What’s Happening?
TRPM3 helps regulate insulin release and cellular energy. If it malfunctions, cells might struggle to manage glucose (sugar) for energy.
Impact: This could worsen energy crashes (post-exertional malaise) and contribute to the “dead battery” feeling in ME/CFS. Poor calcium regulation in muscles might also explain why even mild activity leads to severe fatigue.
5. The Bigger Picture: A Key Piece of the Puzzle?
ME/CFS is likely caused by a mix of genetic, immune, and environmental factors. TRPM3 dysfunction could be one piece of this puzzle. For example: – Genetic mutations in TRPM3 might make some people more prone to ME/CFS.
Viral infections or toxins could “break” TRPM3, triggering symptoms.
Overactive TRPM3 in the brain might disrupt sleep/wake cycles or hormone regulation.
Hope for Treatments? Researchers are exploring drugs that target TRPM3 to: ✅ Calm overactive channels (e.g., using blockers like primidone or certain antidepressants). ✅ Reduce inflammation linked to TRPM3 activation. ✅ Improve cellular energy by restoring calcium balance. However, this is still experimental—no treatments exist yet specifically for TRPM3 in ME/CFS.
Key Takeaway: TRPM3’s role in ME/CFS highlights how tiny cellular “gates” can have big impacts on fatigue, pain, and immune function. While more research is needed
HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entity
Abstract:
Research of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM), two acquired chronic illnesses affecting mainly females, has failed to ascertain their frequent co-appearance and etiology. Despite prior detection of human endogenous retrovirus (HERV) activation in these diseases, the potential biomarker value of HERV expression profiles for their diagnosis, and the relationship of HERV expression profiles with patient immune systems and symptoms had remained unexplored.
By using HERV-V3 high-density microarrays (including over 350k HERV elements and more than 1500 immune-related genes) to interrogate the transcriptomes of peripheral blood mononuclear cells from female patients diagnosed with ME/CFS, FM, or both, and matched healthy controls (n = 43), this study fills this gap of knowledge. Hierarchical clustering of HERV expression profiles strikingly allowed perfect participant assignment into four distinct groups: ME/CFS, FM, co-diagnosed, or healthy, pointing at a potent biomarker value of HERV expression profiles to differentiate between these hard-to-diagnose chronic syndromes.
Differentially expressed HERV-immune-gene modules revealed unique profiles for each of the four study groups and highlighting decreased γδ T cells, and increased plasma and resting CD4 memory T cells, correlating with patient symptom severity in ME/CFS. Moreover, activation of HERV sequences coincided with enrichment of binding sequences targeted by transcription factors which recruit SETDB1 and TRIM28, two known epigenetic silencers of HERV, in ME/CFS, offering a mechanistic explanation for the findings.
Unexpectedly, HERV expression profiles appeared minimally affected in co-diagnosed patients denoting a new nosological entity with low epigenetic impact, a seemingly relevant aspect for the diagnosis and treatment of this prevalent group of patients.
Source: Giménez-Orenga K, Martín-Martínez E, Nathanson L, Oltra E. HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entity. Elife. 2025 May 8;14:RP104441. doi: 10.7554/eLife.104441. PMID: 40338225. https://elifesciences.org/articles/104441 (Full text)
Post-exertional malaise in Long COVID: subjective reporting versus objective assessment
Abstract:
Background: Post-exertional malaise (PEM) is a central feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and has emerged as a prominent feature of Long COVID. The optimal clinical approach to PEM is inconclusive, and studies of the impact of exercise have yielded contradictory results.
Objective: The objective of this study was to examine PEM in Long COVID by assessing the prevalence of self-reported PEM across study cohorts and symptom responses of Long COVID patients to a standardized exercise stressor. Secondarily, Long COVID symptom responses to exercise were compared to those of ME/CFS and healthy volunteers.
Methods: Data from three registered clinical trials comprised four cohorts in this study: Long COVID Questionnaire Cohort (QC; n = 244), Long COVID Exercise Cohort (EC; n = 34), ME/CFS cohort (n = 9), and healthy volunteers (HV; n = 9). All cohorts completed questionnaires related to physical function, fatigue, and/or PEM symptoms. EC also performed a standardized exercise test (cardiopulmonary exercise test, CPET), and the PEM response to CPET was assessed using visual analog scales and qualitative interviews (QIs) administered serially over 72 h. EC PEM measures were compared to ME/CFS and HV cohorts. A secondary analysis of QI explored positive responses to CPET among EC, ME/CFS and HV.
Results: Self-reported PEM was 67% in QC and estimated at 27% in EC. Only 2 of 34 EC patients (5.9%) were observed to develop PEM after a CPET. In addition, PEM responses after CPET in Long COVID were not as severe and prolonged as those assessed in ME/CFS. Twenty-two of 34 EC patients (64.7%) expressed at least one of 7 positive themes after the CPET.
Conclusion: Self-report of PEM is common in Long COVID. However, observable PEM following an exercise stressor was not frequent in this small cohort. When present, PEM descriptions during QI were less severe in Long COVID than in ME/CFS. Positive responses after an exercise stressor were common in Long COVID. Exercise testing to determine the presence of PEM may have utility for guiding clinical management of Long COVID.
Source: Stussman B, Camarillo N, McCrossin G, Stockman M, Norato G, Vetter CS, Ferrufino A, Adedamola A, Grayson N, Nath A, Chan L, Walitt B, Chin LMK. Post-exertional malaise in Long COVID: subjective reporting versus objective assessment. Front Neurol. 2025 Apr 23;16:1534352. doi: 10.3389/fneur.2025.1534352. PMID: 40337174; PMCID: PMC12055772. https://pmc.ncbi.nlm.nih.gov/articles/PMC12055772/ (Full text)
Case Report: The intersection of psychiatry and medicine: diagnostic and ethical insights from case studies
Abstract:
The intersection of psychiatry and medicine presents unique diagnostic and ethical challenges, particularly for conditions involving significant brain-body interactions, such as psychosomatic, somatopsychic, and complex systemic disorders. This article explores the historical and contemporary issues in diagnosing such conditions, emphasizing the fragmentation of medical and psychiatric knowledge, biases in clinical guidelines, and the mismanagement of complex illnesses.
Diagnostic errors often arise from insufficient integration between general medicine and psychiatry, compounded by the reliance on population-based guidelines that neglect individual patient needs. Misclassification of conditions like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme disease, and fibromyalgia as psychosomatic or psychogenic has led to stigmatization and delayed care. While these conditions are referenced as emblematic examples of misclassified and poorly understood disorders, the five clinical cases discussed in this article do not directly illustrate these diseases. Instead, they exemplify shared diagnostic and ethical dilemmas at the medicine–psychiatry interface, including uncertainty, fragmentation, and the risk of epistemic injustice.
The article critically examines terms like medically unexplained symptoms and functional disorders, highlighting their limitations and potential for misuse. Case examples underscore the consequences of diagnostic inaccuracies and the urgent need for improved approaches. Ethical considerations are also explored, emphasizing respecting patient experiences, promoting individualized care, and acknowledging the inherent uncertainties in medical diagnosis.
Advances in technologies such as brain imaging and molecular diagnostics offer hope for bridging the gap between psychiatry and medicine, enabling more accurate assessments and better patient outcomes. The article concludes by advocating comprehensive training at the medicine-psychiatry interface and a patient-centered approach that integrates clinical observation, research insights, and a nuanced understanding of mind-body dynamics.
Source: Monaco F, Vignapiano A, D’Angelo M, Raffone F, Di Stefano V, Boccia A, Longobardi A, Gruttola BD, Fornaro M, Corrivetti G, Martino I, Steardo L, Steardo L Jr. Case Report: The intersection of psychiatry and medicine: diagnostic and ethical insights from case studies. Front Psychiatry. 2025 Apr 22;16:1576179. doi: 10.3389/fpsyt.2025.1576179. PMID: 40330647; PMCID: PMC12053010. https://pmc.ncbi.nlm.nih.gov/articles/PMC12053010/ (Full text)
Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis
Abstract:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogeneous, and systemic disease defined by a suite of symptoms, including unexplained persistent fatigue, post-exertional malaise (PEM), cognitive impairment, myalgia, orthostatic intolerance, and unrefreshing sleep. The disease mechanism of ME/CFS is unknown, with no effective curative treatments.
In this study, we present a multi-site ME/CFS whole-genome analysis, which is powered by a novel deep learning framework, HEAL2. We show that HEAL2 not only has predictive value for ME/CFS based on personal rare variants, but also links genetic risk to various ME/CFS-associated symptoms. Model interpretation of HEAL2 identifies 115 ME/CFS-risk genes that exhibit significant intolerance to loss-of-function (LoF) mutations. Transcriptome and network analyses highlight the functional importance of these genes across a wide range of tissues and cell types, including the central nervous system (CNS) and immune cells.
Patient-derived multi-omics data implicate reduced expression of ME/CFS risk genes within ME/CFS patients, including in the plasma proteome, and the transcriptomes of B and T cells, especially cytotoxic CD4 T cells, supporting their disease relevance. Pan-phenotype analysis of ME/CFS genes further reveals the genetic correlation between ME/CFS and other complex diseases and traits, including depression and long COVID-19.
Overall, HEAL2 provides a candidate genetic-based diagnostic tool for ME/CFS, and our findings contribute to a comprehensive understanding of the genetic, molecular, and cellular basis of ME/CFS, yielding novel insights into therapeutic targets. Our deep learning model also offers a potent, broadly applicable framework for parallel rare variant analysis and genetic prediction for other complex diseases and traits.
Source: Zhang S, Jahanbani F, Chander V, Kjellberg M, Liu M, Glass KA, Iu DS, Ahmed F, Li H, Maynard RD, Chou T, Cooper-Knock J, Zhang MJ, Thota D, Zeineh M, Grenier JK, Grimson A, Hanson MR, Snyder MP. Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis. medRxiv [Preprint]. 2025 Apr 16:2025.04.15.25325899. doi: 10.1101/2025.04.15.25325899. PMID: 40321247; PMCID: PMC12047926. https://pmc.ncbi.nlm.nih.gov/articles/PMC12047926/ (Full text available as PDF file)
Exercise Pathophysiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID: Commonalities Detected by Invasive Cardiopulmonary Exercise Testing
Abstract:
Rationale: There is substantial overlap of exertional symptoms in Long COVID (LC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) including intractable fatigue, post-exertional malaise (PEM), and orthostatic intolerance, but very little objective data liking the two. This study compares exercise pathophysiology in the two disorders and normal controls using invasive cardiopulmonary exercise testing (iCPET).
Methods: Between January 2019 and December 2024, 1,518 patients underwent a clinical iCPET at Brigham and Women’s Hospital. Exclusion criteria included morbid obesity (BMI>40 kg/m2), severe anemia ([Hb]<9.0 g/dL), elite athletes (peak VO2 (pVO2)>120% predicted), sub-maximum effort (RER<1.05), a primary pulmonary mechanical limit (VE @ AT/MVV>0.7), and comorbidities such as active/treated cancer, interstitial lung disease, or other respiratory related diseases. iCPET results from 438 ME/CFS patients, 73 LC patients, and 43 symptomatic but otherwise normal controls were analyzed. pV02, peak cardiac output (pQc), peak right atrial pressure (pRAP), peak systemic oxygen extraction (pSOE; Ca-vO2/[Hb]), and ventilatory inefficiency (VE/VCO2 slope) were compared among groups. Statistical significance was determined using Kruskal-Wallis tests for global comparisons, with post-hoc Dunn tests for pairwise group comparisons. Holm-Bonferroni adjustments were applied to control for multiple comparisons.
Results: LC and ME/CFS displayed reduced pVO2 % predicted compared to controls (LC: 78.4 ± 18%, ME/CFS: 78.1 ± 17%, Controls: 97.5 ± 10%, P≤0.0001). Reduced pQc % predicted was also observed compared to controls (LC: 91.1 ± 18%, ME/CFS: 96.3%, Controls: 101 ± 11%, P≤0.001). pRAP were significantly less compared to controls (LC: 1.1 ± 3.1 mmHg, ME/CFS: 1.3 ± 2.8 mmHg, Controls: 3.6 ± 3.4 mmHg, P≤0.001). Significant reductions in pSOE were seen for LC and ME/CFS (LC: 0.81 ± 0.1, ME/CFS: 0.81 ± 0.1, Controls, 0.91 ± 0.1, P≤0.0001). The only measure with no significant difference between disease and control was VE/VCO2 slope (LC: 31.4 ± 8.4, ME/CFS: 31.6 ± 6.9, Controls: 32.0 ± 6.7, P≥0.261). Most interestingly, no significant differences were seen between the two diseases for any of the analyzed measures (P≥0.245).
Conclusions: We report the largest cohort of ME/CFS and LC investigated with iCPET to date. ME/CFS and LC share symptomatic, reduced aerobic capacity at peak exercise, which is driven by preload insufficiency and impaired systemic O2 extraction, the latter compatible with peripheral left-to-right shunting and/or limb skeletal muscle dysfunction. These findings should drive future diagnostics and personalized medicine in both diseases. We hope these data inform the pending prospective NIH RECOVER iCPET study of LC.
Source: J. Squires, S. Palwayi, P. Li, W. Xiao, K. LeWine, S.W. Johnson, D. Felsenstein, A.B. Waxman, and D.M. Systrom. Exercise Pathophysiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID: Commonalities Detected by Invasive Cardiopulmonary Exercise Testing [abstract]. Am J Respir Crit Care Med 2025;211:A7881. https://www.atsjournals.org/doi/10.1164/ajrccm.2025.211.Abstracts.A7881
Research Supports the Integration of Acupuncture in Mainstream Health Care for the Management of Chronic Diseases
Abstract:
Purpose: To address the role of acupuncture in mainstream health care for symptom relief, condition outcome, pain management, and shared therapy in resolving chronic diseases. This article explores how acupuncture education can adapt to meet the standards required for inclusion in conventional health care.
Objectives: To discuss the future of acupuncture education and its part in training providers for inclusion in a comprehensive health care system that involves physician acupuncturists and licensed acupuncturists for treating and managing specific chronic diseases. To strategize the future of acupuncture education at an advanced clinical level that fosters incorporating acupuncture therapy into selected allopathic settings. To encourage the recognition of translational research for promoting the acceptance of acupuncture by providers and insurers.
Conclusion: Translational research employs clinical evidence to support acupuncture therapy when incorporated into selected areas of allopathic practices, including pain management, palliative care for patients with end-stage cancer, sleep disorders, anxiety disorders, post-traumatic stress, female hormonal conditions such as premenstrual syndrome and menopausal syndrome, as well as chronic fatigue syndromes including Myalgic encephalomyeltitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Advanced clinical training in acupuncture schools and postgraduate certification courses are required to prepare acupuncturists to safely and effectively provide the specialized integrative acupuncture services needed in these clinical areas.
Source: Williams JE, Kim Y, Moramarco J. Research Supports the Integration of Acupuncture in Mainstream Health Care for the Management of Chronic Diseases. Med Acupunct. 2025 Apr 17;37(2):106-111. doi: 10.1089/acu.2024.0108. PMID: 40308724; PMCID: PMC12038303. https://pubmed.ncbi.nlm.nih.gov/40308724/
Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report
Abstract:
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological adverse effect after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations. However, clinicians do not recognize the condition well, and no case report has shown a full recovery.
Case presentation: We present a 65-year-old Japanese female who experienced severe fatigue, postexertional malaise, orthostatic intolerance, and various symptoms after her third SARS-CoV-2 vaccination. Following thorough examinations and excluding other potential diagnoses, she met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The symptoms persisted for 30 months and improved ultimately with comprehensive treatment and a self-management strategy, including pacing management, pharmacological treatments, and psychiatric interventions to support those struggling with the despair over the devastating symptoms.
Conclusion: This case report describes ME/CFS following the SARS-CoV-2 vaccination and its full recovery. It illustrates the importance of considering the differential diagnosis of psychiatric disorders and addressing the condition through psychiatric interventions. Our findings provide new insights into treating ME/CFS and the vaccination-related adverse effects.
Source: Kurotori I, Sasao W, Abe M. Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report. PCN Rep. 2025 Apr 27;4(2):e70111. doi: 10.1002/pcn5.70111. PMID: 40291166; PMCID: PMC12034265. https://pmc.ncbi.nlm.nih.gov/articles/PMC12034265/ (Full text)
The PACE Trial’s GET Manual for Therapists Exposes the Fixed Incremental Nature of Graded Exercise Therapy for ME/CFS
Abstract:
The British National Institute for Health and Care Excellence (NICE) published its updated guidelines for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in October 2021. NICE concluded, after an extensive review of the literature, that graded exercise therapy (GET) is harmful and should not be used, and that cognitive behavioural therapy (CBT) is only an adjunctive and not a curative treatment. An article by White et al., which is written by 51 researchers, claims that there are eight anomalies in the review process and the interpretation of the evidence by NICE. In this article, we reviewed the evidence they used to support their claims.
Their three most important claims are that NICE redefined the disease, that CBT and GET are effective, and that fixed incremental increases are not part of GET. However, our analysis shows that the disease was not redefined by NICE. Instead, it was redefined in the 1990s by a group of doctors, including a number of authors of White et al., when they erased the main characteristic of the disease (an abnormally delayed muscle recovery after trivial exertion, which, over the years, has evolved into post-exertional malaise) and replaced it with chronic disabling severe fatigue. Their own studies show that CBT and GET do not lead to a substantial improvement of the quality-of-life scores or a reduction in CFS symptom count, nor do they lead to objective improvement.
Also, both treatments have a negative instead of a positive effect on work and disability status. Moreover, a recent systematic review, which included one of the authors of White et al., showed that ME/CFS patients remain severely disabled after treatment with CBT. Our analysis of, for example, the PACE trial’s GET manual for therapists exposes the fixed incremental nature of GET.
Why the authors are not aware of that is unclear because eight of them were involved in the PACE trial. Three of them were centre leaders and its principal investigators, four others were also centre leaders, and another one was one of the three independent safety assessors of the trial. Moreover, many of these eight authors wrote, or were involved in writing, this manual.
In conclusion, our analysis shows that the arguments that are used to claim that there are eight anomalies in the review process and the interpretation of the evidence by NICE are anomalous and highlight the absence of evidence for the claims that are made. Furthermore, our analysis not only exposes the fixed incremental nature of GET, but also of CBT for ME/CFS.
Source:Vink M, Partyka-Vink K. The PACE Trial’s GET Manual for Therapists Exposes the Fixed Incremental Nature of Graded Exercise Therapy for ME/CFS. Life (Basel). 2025 Apr 2;15(4):584. doi: 10.3390/life15040584. PMID: 40283139. https://www.mdpi.com/2075-1729/15/4/584 (Full text)