Tag: 2026

Transdisciplinary Expert Statement: care guide for people severely affected by ME/CFS in home-based care

Abstract:

in English, German

Background: Many of those affected by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have significant care needs. However, post-exertional malaise, the defining feature of ME/CFS, means that even minor physical, orthostatic, cognitive, or sensory stressors can trigger a disproportionate worsening of health status, condition and symptoms. This results in specific requirements and significant challenges in home care. Nursing care is still provided predominantly by family caregivers, who frequently lack adequate assistance and support. At the same time, there are significant gaps in knowledge, care infrastructure, and professional guidance for the nursing and healthcare professionals, as well as physicians, involved in providing care.

Objective: The objective of this guide is to structure care measures in a way that prevents overexertion and promotes stability.

Methods: The guide is based on a compilation of practice-oriented measures that have proven effective from the perspective of those affected and family caregivers. These were professionally categorized and further developed by experts in nursing science, physical therapy, general practice and public health.

Results: The guide describes how to adjust key dimensions of care – from nutrition and personal hygiene to communication and managing emotional stress – to disease-specific exertion thresholds. Additionally, requirements for the caregiving relationship and the planning of home visits are outlined and the possibilities of palliative care principles are discussed.

Source: Hermisson J, Schreiner C, Weichselbaumer S, Werner M, Hackl V, Roth J, Leiss S, Maukner AC, Wojczewski S, Hainzl A, Hermisson S, Thonhofer K, Pleschberger S, Hoffmann K. Transdisziplinäres Expert:innen-Statement: Pflegeleitfaden für Menschen mit schwerem ME/CFS in der häuslichen Versorgung [Transdisciplinary Expert Statement: care guide for people severely affected by ME/CFS in home-based care]. Wien Med Wochenschr. 2026 Jun 1. German. doi: 10.1007/s10354-026-01155-6. Epub ahead of print. PMID: 42223876. https://link.springer.com/article/10.1007/s10354-026-01155-6 (Full text)

Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Leading to Assisted Suicide in a Patient in Her Late 30s: A Case Report

Abstract:

A patient in her late 30s developed severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) following an Epstein-Barr virus infection. No distinct autoimmune or autoinflammatory disorder could be identified as the underlying cause of her symptoms, as the observed constellation of cytokine elevations (IL-2, IL-6, and IFN-γ) was not consistent with any known or established disease entity. Despite comprehensive multidisciplinary treatment over two years, including medical, psychological, and rehabilitative approaches, her condition deteriorated, and treatment-related hypersensitivities emerged. The severity and progressive nature of her symptoms, compounded by the absence of effective therapeutic options, ultimately led the patient to pursue assisted suicide.

Source: Opala D, Villiger E, Levenfus I. Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Leading to Assisted Suicide in a Patient in Her Late 30s: A Case Report. Cureus. 2026 May 28;18(5):e109798. doi: 10.7759/cureus.109798. PMID: 42222634; PMCID: PMC13217520. https://pmc.ncbi.nlm.nih.gov/articles/PMC13217520/ (Full text)

Comparative Gut Microbiome Alterations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome & Long COVID-19 Syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 syndrome (LC) show substantial clinical overlap, but direct comparative microbiome studies remain limited.
Methods: In this cross-sectional study, we compared the fecal gut microbiome of patients with ME/CFS, LC, and healthy controls (HC) within a unified analytical framework using 16S rRNA profiling, differential abundance testing, and multivariate modeling. We also examined associations between microbiome variation and questionnaire-derived symptom-domain scores.
Results: Alpha-diversity did not differ significantly among groups, whereas beta-diversity analyses showed small but significant disease-associated community differences with broad overlap between cohorts. Differential abundance analysis identified stronger signals in disease-versus-control contrasts than in the direct ME/CFS vs. LC contrast. Both ME/CFS and LC shared enrichment of Sutterella and depletion of Terrisporobacter and Lachnospiraceae relative to HC. Predicted functional profiling showed shared disease-versus-control changes in pathways related to anaerobic acetate/H2 carbon flow, inositol/polyol degradation, phosphonate/C1-related metabolism, and lysine-derived fermentation. Regression analyses showed the strongest microbiome associations with fatigue-related and physiosomatic domains, while affective, cognitive, and gastrointestinal outcomes showed weaker signals.
Conclusions: Overall, these findings support the presence of overlapping but non-identical gut microbiome alterations in ME/CFS and LC. The results provide a basis for future longitudinal and multi-omics studies aimed at clarifying the stability, functional relevance, and clinical utility of these microbial patterns.
Source: Donchev D, Nikolova R, Vaseva K, Taskov H, Murdjeva M, Maes M, Ivanov IN. Comparative Gut Microbiome Alterations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID-19 Syndrome. Biomedicines. 2026; 14(6):1183. https://doi.org/10.3390/biomedicines14061183 https://www.mdpi.com/2227-9059/14/6/1183 (Full text available as PDF file)

Low-Dose Naltrexone: What is the Evidence? A Narrative Review

Abstract:

Naltrexone is prescribed off-label at low doses, typically 0.5-6.0 mg, for a variety of therapeutic indications. This review evaluates the clinical evidence for low-dose naltrexone (LDN). A literature search was conducted in February 2026 across PubMed, Embase and CINAHL for studies published from 1989 to 2026.

Title and abstract searches for “low dose naltrexone” identified peer-reviewed English-language studies using doses of ≤ 12.5 mg in humans. A total of 105 studies were reviewed, including 15 randomised controlled trials (RCTs) in chronic pain, autoimmune and neuroimmune disorders, gastrointestinal disease, dermatological conditions, post-infectious syndromes, mental health and oncology.

Across these fields, early positive findings from uncontrolled studies were rarely replicated in placebo-controlled trials. Most available evidence consists of case reports and small feasibility studies that are prone to publication bias and rely heavily on subjective outcomes. LDN is generally safe, inexpensive and well tolerated, with most studies using a daily dose of 4.5 mg.

Although these features contribute to its appeal, current evidence does not support routine clinical use. LDN may have a pragmatic role in treatment-resistant cases where standard therapies have failed, provided its experimental status and uncertain efficacy are clearly explained. Larger, well-designed RCTs with objective endpoints, along with N-of-1 approaches to identify potential responders, are needed to clarify its true clinical value.

Source: Gouda AHK, Aitcheson NEC, Steadman KJ. Low-Dose Naltrexone: What is the Evidence? A Narrative Review. Adv Ther. 2026 Apr 30. doi: 10.1007/s12325-026-03612-5. Epub ahead of print. PMID: 42060160. https://link.springer.com/article/10.1007/s12325-026-03612-5 (Full text)

Cardiopulmonary exercise test results do not change over two sequential days in patients with chronic fatigue syndrome

Abstract:

Background: Two consecutive cardiopulmonary exercise tests (CPETs) performed 24 hours apart are increasingly used to determine post-exertional malaise (PEM) and disability in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Declines in functional capacity on Day 2 reflect impaired recovery and PEM. However, reports have variably described a reduction in peak oxygen consumption (VO2) and/or VO2 at the anaerobic ventilatory threshold (VT). Given the inconsistent findings, we sought to replicate the studies by performing sequential 2-day CPETs in ME/CFS and age- and sex-matched sedentary controls.

Methods: Accordingly, maximal bicycle ergometer CPETs were performed on two consecutive days in 58 patients with ME/CFS (mean age 38.6 ± 9.6 years, Body Mass Index (BMI) 24.1 ± 3.3 kg/m2, 11 men and 47 women) and 25 age-matched sedentary control (CON) subjects (age 38.2 ± 9.9 years, BMI 24.2 ± 3.4 kg/m2, 5 men and 20 women). Peak VO2 was reported as the highest 30-sec average; VT was selected as the nadir of the VE/VO2 and PETCO2 curves, and VE/VCO2 as the slope throughout exercise.

Findings: For ME/CFS and CON subjects, there were no significant changes in Peak VO2 between Day 1 and Day 2 studies (ME/CFS Day 1, 22.3 ± 5.4; Day 2, 22.5 ± 5.4 mL·kg-1·min-1; CON Day 1, 23.4 ± 3.5; Day 2, 22.8 ± 3.6 mL·kg-1·min-1; NS). Similarly, VO2VT and VE/VCO2 slopes were not significantly different between the ME/CFS patients and CON, and on Day 2, they did not show any differences within or between groups. Peak heart rate was significantly higher in CON versus ME/CFS. The level of perceived exertion was significantly greater at all levels of exercise on the Day 1 and Day 2 tests for ME/CFS patients versus CON.

Interpretation: Our data indicate that 2-day CPET provides exercise-related results that are the same in ME/CFS patients and CON subjects. ME/CFS patients have a greater perception of exertion throughout exercise and a lower maximum heart rate than CON. The data do not support using the 2-day CPET protocol to define PEM or disability.

Source: Mancini DM, Cook DB, Brunjes DL, Soto T, Blate M, Quan P, Yamazaki T, Norweg A, Natelson BH. Cardiopulmonary exercise test results do not change over two sequential days in patients with chronic fatigue syndrome. Front Physiol. 2026 May 13;17:1816082. doi: 10.3389/fphys.2026.1816082. PMID: 42212259; PMCID: PMC13213420. https://pmc.ncbi.nlm.nih.gov/articles/PMC13213420/ (Full text)

Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long Coronavirus Disease 2019 (long COVID) are complex chronic conditions that often follow infectious triggers with overlapping clinical features but poorly defined pathophysiological relationships. This study aimed to identify disease-specific immune signatures through multiparameter immunophenotyping of monocytes, dendritic cells, and T cell subsets.

A total of 207 participants were included (ME/CFS: n = 103; long COVID: n = 63; healthy controls: n = 41). Peripheral blood mononuclear cells were analyzed using multiparameter flow cytometry. Statistical analyses included non-parametric testing, age-adjusted Analysis of covariance (ANCOVA), correlation network analysis, and principal component analysis (PCA).

Long COVID was characterized by increased M2-like monocyte polarization, elevated CD80 expression across monocyte subsets, expansion of dendritic cells, and reduced expression of activation markers, indicating persistent immune activation with features of immune exhaustion.

In contrast, ME/CFS exhibited reduced costimulatory molecule expression, impaired C-C chemokine receptor type 7 (CCR7)-mediated immune cell trafficking, and less coordinated activation patterns, consistent with a state of immune suppression. Correlation network analysis revealed more extensive and integrated immune interactions in long COVID, while PCA identified distinct immunophenotypic components and enabled moderate discrimination between the two conditions.

These findings demonstrate that ME/CFS and long COVID are characterized by distinct immune profiles, supporting the concept of divergent immunopathological mechanisms. The identified signatures may contribute to biomarker development and guide targeted therapeutic approaches.

Source: Petrov S, Bozhkova M, Ivanovska M, Kalfova T, Dudova D, Todorova Y, Dimitrova R, Murdjeva M, Taskov H, Nikolova M, Maes M. Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID. Int J Mol Sci. 2026 May 17;27(10):4488. doi: 10.3390/ijms27104488. PMID: 42196466; PMCID: PMC13206834. https://pmc.ncbi.nlm.nih.gov/articles/PMC13206834/ (Full text)

Toward a Molecular Reclassification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Integrating Multi-Omics, Machine Learning, and Precision Medicine

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system disease characterized by a multitude of symptoms across various organ systems. Diagnosis has relied heavily on heterogeneous clinical symptom presentation and evolving case definitions, with treatment focused on addressing presenting symptoms due to the paucity of validated biomarkers. Meanwhile, advances have been made in understanding the underlying pathophysiology through strong epidemiologic, clinical, and basic science studies. This narrative review synthesizes recent advances that are likely to drive a shift in understanding from symptom-based classification toward a molecularly defined understanding of the disease.

This shift in understanding will likely provide the foundation for future research efforts focused on targeting diagnosis and treatment more effectively. Specifically, we reference the identification of rare genetic risk variants through the HEAL2 deep learning framework, the large-scale DecodeME genome-wide association study, and dynamic epigenetic markers of disease state.

In addition, the findings revealed the downstream consequences of this genetic and epigenetic priming: chronic innate immune activation, CD8+ T cell exhaustion characterized by upregulation of the exhaustion-driving transcription factors Thymocyte Selection-Associated HMG Box (TOX) and Eomesodermin (EOMES), and a cellular energy crisis centered on mitochondrial dysfunction. Furthermore, results of recent studies have revealed sex-specific transcriptomic and proteomic signatures of maladaptive recovery.

We also highlight the role of machine learning and artificial intelligence integrations in translating high-dimensional multi-omics data into actionable biological insights, including the identification of monocyte subsets via Positive Unlabeled Learning, circulating cell-free RNA diagnostic signatures, and integrated multi-modal disease models such as BioMapAI.

The combination of these findings, which highlight multiple identifiable mechanisms of molecular activity, support the feasibility of molecular subtyping, precision diagnostics, and targeted therapeutic strategies for ME/CFS.

Source: Frank J, Nesterovitch N, Movva C, Klimas NG, Nathanson L. Toward a Molecular Reclassification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Integrating Multi-Omics, Machine Learning, and Precision Medicine. Int J Mol Sci. 2026 May 15;27(10):4436. doi: 10.3390/ijms27104436. PMID: 42196410; PMCID: PMC13207433. https://pmc.ncbi.nlm.nih.gov/articles/PMC13207433/ (Full text)

Human Endogenous Retroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Roles in Pathogenesis, Immunity, Biomarkers and Therapeutics

Abstract:

Human endogenous retroviruses (HERVs) are potential driving forces of the pathophysiology of Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), linking post-infectious immune dysfunction to chronic inflammation and immune and neurocognitive dysfunction that are hallmark features of ME/CFS.

Accumulating evidence from related autoimmune diseases and cancers has shown that reactivated HERVs can contribute to disease pathogenesis by amplifying immune activation through viral protein-mediated innate sensing, long terminal repeat (LTR)-driven transcription, and disrupting epigenetic silencing. HERV signatures are therefore promising biomarkers for diagnosis, patient stratification for drug-repurposing trials, and therapy monitoring.

Accumulating evidence suggests a possible correlation between HERV expression and ME/CFS symptom severity, alterations in immune phenotypes, function and inflammatory gene networks. Importantly, locus-specific HERV profiling is a promising approach for distinguishing ME/CFS from overlapping or co-morbid conditions and healthy controls. Furthermore, HERV-targeted antibodies, immune modulators, epigenetic and antiviral interventions offer promise as concomitant therapeutic strategies for ME/CFS.

Additional research incorporating viromics and other-omics validation, functional assays, and HERV-stratified clinical trials is now needed to realise this potential and to transform ME/CFS from a symptom-based syndrome into a mechanism-driven, treatable condition.

Source: Perera KD, Oltra E, Carding SR. Human Endogenous Retroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Roles in Pathogenesis, Immunity, Biomarkers and Therapeutics. Int J Mol Sci. 2026 May 12;27(10):4309. doi: 10.3390/ijms27104309. PMID: 42196290; PMCID: PMC13207908. https://pmc.ncbi.nlm.nih.gov/articles/PMC13207908/ (Full text)

Shared genetic risk between functional somatic syndromes, internalizing disorders, and immune-mediated diseases: a twin-sibling study

Abstract:

Functional somatic syndromes frequently co-occur with internalizing disorders such as anxiety disorders and major depressive disorder. Both show familial associations with immune-mediated diseases. Here, we estimate genetic and environmental contributions to functional somatic syndromes and their overlap with immune-mediated diseases, with internalizing disorders included for comparison.

The study sample consisted of 6,097,372 Swedish twins, full siblings, and half-siblings born between 1945 and 2003. From nationwide registers covering inpatient, outpatient and primary care, we extracted ICD diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), irritable bowel syndrome (IBS), major depression, anxiety disorders, and immune-mediated diseases (consisting of autoimmune and autoinflammatory diseases).

We used bivariate twin-sibling structural equation modeling to estimate genetic and environmental correlations. We found that the heritability of functional somatic syndromes and internalizing disorders ranged from 15 to 44%, with the unique environment explaining 49-84% of the variance. We estimated the heritability of immune-mediated diseases at 37% (95% CI 36-38%), with a unique environmental component of 63% (95% CI 62-63%). Regarding the genetic correlations with immune-mediated diseases, fibromyalgia showed the strongest genetic correlation (rA = 0.52, 95% CI 0.45-0.63), IBS, ME/CFS, and major depression showed more modest genetic correlations (rA range 0.19-0.29), and anxiety disorders showed minimal genetic correlation (rA = 0.04, 95% CI 0.00-0.08).

In summary, fibromyalgia, and to a lesser degree other functional somatic syndromes and major depression, share genetic risk factors with immune-mediated diseases. These findings suggest that immune-related genetic risk factors contribute to the etiology of fibromyalgia and, to a lesser extent, other functional disorders and major depression.

Source: Steen OD, Ohlsson H, van Ockenburg SL, Kendler KS, Rosmalen JGM, Sundquist K, van Loo HM. Shared genetic risk between functional somatic syndromes, internalizing disorders, and immune-mediated diseases: a twin-sibling study. Brain Behav Immun. 2026 May 25:106837. doi: 10.1016/j.bbi.2026.106837. Epub ahead of print. PMID: 42190845. https://www.sciencedirect.com/science/article/pii/S0889159126005854 (Full text)

Deficient TRPM3-linked mitochondrial Ca2+ influx in natural killer cells associated with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic illness, commonly associated with dysregulation of the immune system including reduced cytotoxicity of natural killer (NK) cells and post-exertional neuroimmune exhaustion. Previously, transient receptor potential melastatin 3 (TRPM3) ion channel impairment associated with reduced Ca2+ mobilisation in NK cells from ME/CFS patients was reported. To further explore the pathomechanisms involved in ME/CFS, we investigated the downstream impact of TRPM3 ion channel dysfunction on mitochondrial Ca2+ mobilisation in NK cells.

Method: Fluorescence live-cell imaging was used to investigate Ca2+ mobilisation in NK cells of (N = 10) ME/CFS, classified using Canadian Consensus Criteria, and (N = 10) healthy control (HC) participants. Cytoplasmic and mitochondrial Ca2+ entry was determined using Fluo-8 AM and Rhod-2 AM Ca2+ indicators, respectively. The effect of TRPM3 modulation on Ca2+ mobilisation ex vivo, was examined using pregnenolone sulfate and ononetin to activate and inhibit the channel, respectively.

Results: Cytosolic Ca2+ influx amplitude and slope were significantly reduced (p < 0.001), with a significantly shorter T1/2 response (p = 0.001) in ME/CFS compared to HC. Ca2+ influx amplitude (p < 0.001) and slope (p < 0.041) into the mitochondria were significantly higher in ME/CFS compared to HC. TRPM3 activation triggered pronounced cytosolic response (P < 0.001) accompanied by mitochondrial Ca2+ increase in HC. TRPM3-dependent cytosolic and mitochondrial Ca2+ mobilisation (P < 0.015) were significantly reduced with a shorter T1/2 response (p < 0.02) in ME/CFS compared to HC.

Conclusion: The results demonstrate that altered TRPM3-mediated cytosolic Ca2+ influx may significantly impact Ca2+ mobilisation into the mitochondria of people with ME/CFS. Alterations that interfere with the optimal function of Ca2+ permeable channels may cumulatively impact downstream signalling, leading to detrimental cellular consequences. Collectively these findings provide an avenue for further studies on the physiological functions of TRPM3 ion channel and its role in ME/CFS.

Source: Magawa CT, Eaton-Fitch N, Muraki K, Marshall-Gradisnik S. Deficient TRPM3-linked mitochondrial Ca2+ influx in natural killer cells associated with myalgic encephalomyelitis/chronic fatigue syndrome. BMC Immunol. 2026 May 23. doi: 10.1186/s12865-026-00849-1. Epub ahead of print. PMID: 42177403. https://link.springer.com/article/10.1186/s12865-026-00849-1 (Full text)