{ "condition": "ME/CFS – Myalgic Encephalomyelitis / Chronic Fatigue Syndrome", "key": "me-cfs", "last_updated": "2026-07-06T16:45:30.923262Z", "count": 75, "source": "PubMed (NCBI)", "studies": [ { "pmid": "42404713", "title": "Cognitive impairment and prefrontal TGF-β1 elevation in a rat model of fatigue.", "pub_date": "2026-07-06", "journal": "Frontiers in psychiatry", "authors": "Wu, Yingru, Wen, Xuan, Fang, Zeman, Zhang, Jinling et al.", "abstract": "Chronic fatigue syndrome (CFS) is a complex disorder of unknown etiology, characterized by persistent fatigue unrelieved by rest and accompanied by cognitive dysfunction. While dysregulated cytokines are implicated in CFS pathogenesis, the role of anti-inflammatory transforming growth factor β1 (TGF-β1) remains poorly defined. This study investigated central and peripheral TGF-β1 dysregulation and cognitive function in a rat model of fatigue induced by 10-day repetitive sleep deprivation with intermittent rest. Rats were randomly divided into the control group and the fatigue group. Behavioral tests including open field test and Y-maze test were performed after the end of fatigue-loading procedure. Peripheral and central TGF-β1 levels were detected. Rats in the fatigue group exhibited unchanged daytime short-term locomotor activity but significantly increased anxiety-like behavior in the open field test. In the Y-maze test, the fatigue group showed markedly reduced spontaneous alternation rates compared to controls. Furthermore, prefrontal cortical TGF-β1 levels were elevated in fatigued rats, whereas neither peripheral nor striatal TGF-β1 differed between groups. These findings demonstrate that the 10-day repetitive sleep deprivation with intermittent rest fatigue model induces cognitive impairment and increased anxiety-like behavior, with selective prefrontal TGF-β1 upregulation. The concomitant elevation of prefrontal TGF-β1 and cognitive deficits suggests a potential role for central TGF-β1 signaling in the pathophysiology of mental fatigue, although the precise nature of this relationship remains to be elucidated.", "url": "https://pubmed.ncbi.nlm.nih.gov/42404713/" }, { "pmid": "42403482", "title": "Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS.", "pub_date": "2026-07-06", "journal": "Frontiers in neuroscience", "authors": "Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Inderyas, Maira, Barnden, Leighton", "abstract": "The glymphatic system is a recently discovered brain waste clearance system that is mostly active during sleep and disengaged during wakefulness. Impaired glymphatic function leads to the deposition of metabolic waste products in the brain potentially causing inflammation leading to various symptoms in ME/CFS. While the glymphatic function has been assessed in other neurodegenerative diseases using 'diffusion tensor imaging along the perivascular space' (DTI-ALPS), it has not been studied in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). This preliminary study investigates glymphatic function in 58 participants (ME/CFS = 31 and healthy controls = 27) using the DTI-ALPS index derived from DTI data acquired with 3 T MRI. The bilateral hemispheric DTI-ALPS index was estimated to assess glymphatic function, and an asymmetry index was calculated to determine interhemispheric asymmetry in glymphatic function. We found that the global DTI-ALPS index was significantly lower in ME/CFS patients compared to healthy controls (ME/CFS: 1.44 ± 0.086; healthy controls: 1.51 ± 0.11,", "url": "https://pubmed.ncbi.nlm.nih.gov/42403482/" }, { "pmid": "42399727", "title": "Association between light exposure patterns and multidimensional health outcomes in individuals with myalgic encephalomyelitis/chronic fatigue syndrome: findings from an observational cross-sectional cohort study.", "pub_date": "2026-07-04", "journal": "Journal of translational medicine", "authors": "Cambras, Trinitat, Domingo, Joan Carles, Sanmartín-Sentañes, Ramon, Alegre-Martín, José et al.", "abstract": "Light is a major environmental factor regulating circadian rhythms, sleep- wake cycles, and mood-related behaviors. Patients with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often experience circadian disruption and poor sleep quality, which severely compromise their quality of life; however, the relationship between light exposure and illness severity remains largely unknown. An observational cross-sectional cohort secondary study used collected data from 100 ME/CFS patients and 56 healthy controls to explore the impact of spontaneous light exposure on multidimensional health status and circulating biochemical parameters. Demographic and clinical features were assessed using validated patient-reported outcome measures. Light intensity, wrist temperature, and physical activity were continuously monitored at home over one week using wrist-worn actigraphy. Light intensity during predefined intervals and rhythmic variables of light cycle were calculated. Principal component analysis (PCA) was applied to reduce dimensionality of light variables. Multivariable analysis was performed adjusting for age, sex, body mass index, and physical activity. Following PCA of the light patterns, two components emerged across groups with high consistency: PC1 (explaining 61.7% of the total variance) reflected higher daytime light and rhythm stability, and PC2 (explaining 16.1%) represented nocturnal/early-morning light and rhythm instability. In ME/CFS patients, light variables were more extensively associated with clinical outcomes measures (FIS-40, PSQI and SF-36) than in healthy controls (all p < 0.05). Furthermore, PC2 was associated with higher levels of VCAM-1 and triglycerides, and lower serotonin concentrations (all p < 0.05). Four distinct light patterns were identified based on PCA scores: nocturnal light, healthy, adverse, and low diurnal light. ME/CFS patients exhibiting the healthy light pattern showed significantly lower fatigue, fewer sleep complaints, reduced autonomic dysfunction, and higher quality of life compared to those with the adverse light pattern (all p < 0.05). No significant differences were observed among healthy controls. Light exposure patterns show distinct associations with symptom variability in ME/CFS compared to healthy controls. More stable daytime light appears to relate to better symptom profiles, whereas irregular exposure and nocturnal light are linked to poorer health outcomes. Although causality cannot be inferred, these findings highlight light exposure as a potentially modifiable, non-invasive target for behavioral interventions aimed at improving the quality of life in ME/CFS, representing a promising emerging for future translational research.", "url": "https://pubmed.ncbi.nlm.nih.gov/42399727/" }, { "pmid": "42396162", "title": "Higher-order brain processes, rather than early processing, underlie sensory problems in ME/CFS: evidence from ERPs.", "pub_date": "2026-07-03", "journal": "Frontiers in medicine", "authors": "Kumar, Sanjay, Veldhuis, Alfred, Yazdani, Farzaneh", "abstract": "Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) experience significant sensory problems that affect their personal, social and occupational life. However, there is no clear understanding of how the sensory problems manifest in ME/CFS. Neuroimaging studies have provided indirect evidence of the involvement of sensory brain areas in ME/CFS. This novel systematically examined the role of early sensory processing and late information processing brain systems in ME/CFS patients. The participants consisted of 31 ME/CFS patients and 30 healthy matched controls. Measures of subjective experience of sensory problems as well as event-related brain potentials (ERPs) on an auditory paired click task and an auditory oddball task were collected. ME/CFS patients reported significantly higher sensory problems compared to the control group. On the ERP measures, the ME/CFS group was not significantly different on the P50 suppression index than the control group. However, the ME/CFS group showed a significantly reduced P300 potential compared with the control group. These findings suggest that the higher-order control-based brain mechanism contributes to the sensory problems experienced by ME/CFS patients. These findings could have profound implications for targeted interventions directed towards higher-order brain systems, rather than the sensory systems, to address challenges related to sensory processing problems in ME/CFS.", "url": "https://pubmed.ncbi.nlm.nih.gov/42396162/" }, { "pmid": "42391726", "title": "Therapeutic plasma exchange and immunomodulatory strategies in post-infectious syndromes: A review of immune dysregulation in PTLDS, long COVID, ME/CFS, and PANS/PANDAS.", "pub_date": "2026-07-03", "journal": "Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis", "authors": "Kaplan, Gary", "abstract": "Post-infectious syndromes including post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute-onset neuropsychiatric syndrome (PANS)/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) share overlapping clinical phenotypes characterized by fatigue, cognitive dysfunction, sleep disturbance, and neuropsychiatric symptoms. Increasing evidence suggests that immune dysregulation-including persistent inflammation, autoantibody production, and cellular immune dysfunction-may underlie these conditions. This narrative review synthesizes peer-reviewed literature describing immune abnormalities across these syndromes and evaluates the rationale for immunomodulatory therapies, including intravenous immunoglobulin (IVIG), rituximab, and therapeutic plasma exchange (TPE). Evidence supporting immune-targeted treatment strategies is strongest in subsets of patients with identifiable immunologic abnormalities. Notably, the phase III RituxME trial in ME/CFS and a phase II trial of TPE in post-COVID condition both failed to demonstrate efficacy in unselected populations, reinforcing the importance of biomarker-guided patient stratification. TPE functions by removing circulating immune complexes, autoantibodies, and inflammatory mediators, and observational data suggest benefit in patients with demonstrable autoantibody burden. Further controlled studies incorporating immunologic phenotyping and early intervention are needed to define the therapeutic role of immune-directed interventions across these conditions.", "url": "https://pubmed.ncbi.nlm.nih.gov/42391726/" }, { "pmid": "42383026", "title": "Exploring the mechanisms of acupuncture in improving cognitive function in post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome: study protocol for a randomized controlled trial using multimodal MRI.", "pub_date": "2026-07-01", "journal": "Frontiers in neurology", "authors": "Luo, Tingting, Luo, Yang, Huang, Liang, Jin, Hongjiao et al.", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common sequela following COVID-19. Although cognitive dysfunction is one of the most debilitating symptoms in ME/CFS, effective therapies are limited. Acupuncture is an important complementary and alternative therapy for ME/CFS and has been shown to have positive effects on cognitive dysfunction in other diseases. However, the effect and mechanism of acupuncture in treating cognitive dysfunction in post-COVID-19 ME/CFS(PCME/CFS) remain unclear. In this study, we designed a randomized controlled trial to evaluate the efficacy of acupuncture treatment in improving cognitive function in PCME/CFS and to investigate the neural mechanisms of acupuncture using multimodal magnetic resonance imaging (MRI) techniques. A total of 129 patients and 30 healthy controls (HCs) will be enrolled. The 129 patients with PCME/CFS will be randomly assigned in a 1:1:1 ratio to a verum acupuncture (VA), sham acupuncture (SA), or a waitlist control group. Participants in the VA and SA groups will receive three sessions of treatment per week for 8 weeks, while patients in the waitlist control group will be treated after the 8-week waiting period. The primary outcome is the change in the Symbol Digit Modalities Test (SDMT) score from baseline to week 8. The secondary outcome measures include changes from baseline to endpoint (week 8) in cognitive performance as assessed by the Digit Span Test (DST), Trail Making Test (TMT), Rey Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth complex figure test (RCFT), Stroop Color and Word Test (SCWT), phonemic fluency test, category fluency test, action fluency test, and 30-item Boston Naming Test (BNT-30). In addition, changes in hippocampal metabolites and resting-state functional connectivity(RSFC) will be examined using The results of this study will provide preliminary evidence regarding the efficacy of acupuncture therapy in improving cognitive function in PCME/CFS and will explore whether acupuncture improves cognitive function in this disease by modulating metabolism and RSFC in the hippocampus. www.clinicaltrials.gov, identifier: NCT07357688.", "url": "https://pubmed.ncbi.nlm.nih.gov/42383026/" }, { "pmid": "42375682", "title": "Exploring differences in protein cargo of extracellular vesicles from ME/CFS patient plasma compared to healthy controls.", "pub_date": "2026-06-30", "journal": "Biochemistry and biophysics reports", "authors": "Rydland, Anne, Yran, Elena Støvring, Nyman, Tuula A, Strand, Elin Bolle et al.", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by post-exertional malaise, fatigue and pain. Yet, its underlying biological mechanisms remain poorly understood. Extracellular vesicles (EVs) are nanoparticles carrying biological cargo and are involved in cell-cell communication. Plasma EVs reflect several disease states and may serve as minimally invasive biomarkers. In this exploratory study, we characterized the plasma EV profiles of ME/CFS patients (N = 49) and healthy controls (N = 50), by enriching for EVs by size-exclusion chromatography coupled to high-resolution quantitative proteomics. The ME/CFS patients had significantly higher concentrations of EVs than healthy controls. Among the 424 detected proteins included for analyses, 11 had different levels in EVs from ME/CFS patients. The ME/CFS associated EV proteins appear to mainly originate from erythroid cells, hepatocytes and plasma B cells, based on their tissue expression. Albeit differences in EV protein levels did not withstand correction for multiple testing, our study is the largest to date, thereby encouraging future investigations on the role of EV and its cargo in ME/CFS.", "url": "https://pubmed.ncbi.nlm.nih.gov/42375682/" }, { "pmid": "42365408", "title": "Effect of \"Tongdu Yupi Tiaoshen\" electroacupuncture on behavioral performance and hippocampal structure and function in chronic fatigue syndrome rats.", "pub_date": "2026-06-28", "journal": "Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan", "authors": "Yuanyuan, Q U, Chuwen, Feng, Weibo, Sun, Yuying, Shao et al.", "abstract": "To investigate the effects of electroacupuncture intervention on behavioral performance, hippocampal structure, and function in chronic fatigue syndrome (CFS) rats and to explore the underlying mechanisms. Specific pathogen free-grade male Sprague-Dawley rats were randomly allocated into a control group (Con group, Behavioral assessments demonstrated that electroacupuncture intervention significantly improved rat performance as measured by GSQS, MWMT, OFT, and Exhaustive Treadmill Test. Both HE and Nissl staining results confirmed that, compared with the blank control group, the model group exhibited abnormal cellular morphology, disorganized arrangement, and reduced Nissl bodies in the hippocampal CA1 region. These pathological alterations were ameliorated in the electroacupuncture group relative to the model group. 18F-FDG PET/CT imaging revealed that following treatment, the mean and maximum standardized uptake values (SUV) in the anterior-dorsal and posterior hippocampus were significantly decreased in the Mod group compared to the Con group. In contrast, electroacupuncture treatment significantly increased both SUV-mean and SUV-max in these hippocampal subregions in the EA group relative to the Mod group (all Electroacupuncture intervention alleviated cognitive impairment, hippocampal pathological structural changes, and glucose metabolism dysfunction in a rat model of chronic fatigue syndrome induced by an improved chronic multi-factor compound stress stimulation method.", "url": "https://pubmed.ncbi.nlm.nih.gov/42365408/" }, { "pmid": "42360043", "title": "Comparison of Proteomic Analysis of Cerebrospinal Fluid From Neurological Patients With and Without Amyotrophic Lateral Sclerosis.", "pub_date": "2026-06-27", "journal": "Journal of neurochemistry", "authors": "Sabetta, Eleonora, Rallmann, Karin, Taba, Pille, Pfaff, Abigail L et al.", "abstract": "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by progressive muscle weakness in both bulbar and extremity muscles, leading to a diverse clinical phenotype with motor and non-motor symptoms. Approximately 85% of ALS cases are sporadic (sALS), while the remaining 10%-15% are familial (fALS). Biological biomarkers of sporadic ALS remain poorly understood, hindering precise patient screening, delaying diagnosis and negatively affecting prognosis. This study aims to identify potential proteomic biomarkers by comparing the cerebrospinal fluid (CSF) of sALS patients with that of patients suffering from other neurological diseases. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for proteomic profiling of CSF samples from 24 sALS patients and 26 patients with other neurological diseases. The complete protein expression profiles were compared using a two-tailed Student's t-test, with a p < 0.05 considered statistically significant with additional FDR correction at the 0.1 level. Proteomic analysis of CSF samples identified significant quantitative changes in 96 proteins with threshold p < 0.05 and 74 proteins with FDR < 0.1 between sALS and non-ALS patients, including alterations in proteins associated with neurodegenerative processes, such as amyloid precursor proteins and inflammatory markers. CSF proteomic analysis reveals altered inflammatory and neurodegenerative metabolic pathways, providing valuable insights into the proteomic landscape of sALS. Several dysregulated proteins were consistent with the disease mechanisms highlighted in previous studies. These findings represent a step forward in developing personalised approaches for diagnosing and managing the disease.", "url": "https://pubmed.ncbi.nlm.nih.gov/42360043/" }, { "pmid": "42358486", "title": "Redefining pandemic resilience: a roadmap for post-infectious syndrome preparedness and health system transformation.", "pub_date": "2026-06-26", "journal": "Frontiers in health services", "authors": "Schieffer, Bernhard", "abstract": "Post-infectious syndromes like Long COVID and ME/CFS lead to disability and economic losses globally, especially in lower-income countries. These involve complex multisystem issues such as immune disturbances, inflammation, autonomic dysregulation, vascular problems, altered metabolism, and tissue damage. Re-infections increase the risk of disability and complications. Healthcare delays diagnosis and neglects long-term effects. We propose a three-part healthcare approach: primary care screening with digital tools, regional testing centers, and specialized Centers of Excellence for complex cases. An integrated infrastructure with registries, patient data, and wearables supports personalized care and surveillance. Policies should include disability benefits, rehab, infection control, and innovative funding. Healthcare must be accessible via mobile and community efforts, integrated into pandemic plans. The goal is to reduce morbidity and improve socioeconomic resilience.", "url": "https://pubmed.ncbi.nlm.nih.gov/42358486/" }, { "pmid": "42357670", "title": "Human Herpesvirus-6A and -6B (HHV-6A and HHV-6B): The Role of Roseoloviruses in Neurological Dysfunction and the Mechanisms of Viral-Induced Epileptogenesis.", "pub_date": "2026-06-26", "journal": "Viruses", "authors": "Bahramian, Elham, Bajpai, Ananya, Yang, Xue, Cairns, Dana M et al.", "abstract": "Human herpesvirus-6 consists of a pair of viral species, HHV-6A and HHV-6B, which are neurotropic with the ability to invade, persist, and reactivate within the nervous system. Accumulating evidence links HHV-6 to epilepsy and other neuropathologies, including: multiple sclerosis, chronic fatigue syndrome, and neurodegeneration. Yet, mechanisms by which these viruses induce neurological disorders, including their role in epileptogenesis, remain unknown. It has been demonstrated that HHV-6 exhibits tropism for astrocytes, oligodendrocytes, and neurons. Thus, HHV-6 can perturb cellular homeostasis, neuronal signaling, and immune regulation, astrocytic glutamate clearance, GABAergic inhibition, and cholinergic or monoaminergic neurotransmission yielding network hyperexcitability. It is also reported that HHV-6 can activate neuroinflammation through Toll-Like Receptor (TLR), cytokine, and/or NF-κB activation, which facilitates neuronal injury and network instability. Indeed, a suite of converging processes suggest a multifactorial nature for HHV-6 related neuropathology. Despite robust experimental and clinical data, definitive causal relationships between HHV-6 and epilepsy (or induction of neurodegeneration) remain elusive. This review discusses evidence for roseolovirus-induced neurological dysfunction and disorders commonly associated with HHV-6A and HHV-6B infections. A preponderance of clinical and experimental evidence suggests that differential tropism for distinct neuronal neurotransmitter chemotypes and glia as well as systemic effects are involved in roseolovirus-mediated neurological disease.", "url": "https://pubmed.ncbi.nlm.nih.gov/42357670/" }, { "pmid": "42356126", "title": "Long-Term Follow-Up of Women with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A 16-Year Longitudinal Study.", "pub_date": "2026-06-26", "journal": "Medicina (Kaunas, Lithuania)", "authors": "Tomić, Slavica, Pastornački, Aleksandra, Drljača, Maja, Glogovac, Jelena et al.", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/42356126/" }, { "pmid": "42356003", "title": "Multimorbidity in Chronic Overlapping Pain Conditions: From Burden to Integrated Care.", "pub_date": "2026-06-26", "journal": "Journal of clinical medicine", "authors": "d'Incau, Emmanuel, Kaplan, Chelsea Marie, Micoulaud-Franchi, Jean-Arthur, Veasley, Christin et al.", "abstract": "Chronic overlapping pain conditions (COPCs) refer to a set of chronic pain disorders that frequently co-occur and may involve partially overlapping mechanisms. The U.S. National Institutes of Health currently recognizes ten COPCs: fibromyalgia, painful temporomandibular disorders, chronic low back pain, chronic migraine headache, chronic tension-type headache, irritable bowel syndrome, endometriosis, interstitial cystitis/bladder pain syndrome, vulvodynia, and myalgic encephalomyelitis/chronic fatigue syndrome. When multiple COPCs coexist, they are associated with a disproportionate multimorbidity burden, including greater pain, poorer psychological well-being, functional limitations, disability, fatigue, sleep disturbances, diminished quality of life, and increased healthcare utilization. Despite their impact, COPCs remain under-recognized, underdiagnosed, and undertreated. Combining structured literature searches and citation tracking with narrative syntheses, this review examines comorbid relationships, the burden of multimorbidity, and potentially overlapping nociplastic mechanisms. By adopting a multimorbidity-based perspective rather than a one-disease, one-treatment approach, it highlights barriers to care-including limited clinical awareness, under-recognition of additional COPCs, limited mechanistic understanding, and fragmented care-and proposes integrated strategies emphasizing prevention, systematic screening, mechanism-informed assessment, and coordinated, patient-centered multimodal management.", "url": "https://pubmed.ncbi.nlm.nih.gov/42356003/" }, { "pmid": "42351611", "title": "Comparative Gut Microbiome Alterations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID-19 Syndrome.", "pub_date": "2026-06-26", "journal": "Biomedicines", "authors": "Donchev, Deyan, Nikolova, Ralitsa, Vaseva, Katya, Taskov, Hristo et al.", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/42351611/" }, { "pmid": "42334638", "title": "Effect of photobiomodulation on pain and quality of life in fibromyalgia syndrome: a systematic review.", "pub_date": "2026-06-23", "journal": "Lasers in medical science", "authors": "G A, Swathi, Maiya, G Arun, Shetty, Shiran, Abrahamse, Heidi et al.", "abstract": "Fibromyalgia Syndrome (FMS) is a chronic pain disorder characterized by widespread pain and central sensitization that significantly impacts the quality of life (QoL). For management to be effective, a multidisciplinary approach to care is typically required. Photobiomodulation therapy (PBMT), a non-pharmacological treatment, has garnered attention lately, though its clinical relevance and applications are not well defined. The objective of this review was to assess the effectiveness of PBMT in reducing FMS symptoms. This systematic review was registered at PROSPERO (CRD420251084730) and conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines. A total of seven randomized controlled trials were identified following an extensive literature search across various databases, including PubMed, Scopus, Web of Science, the Cochrane Library, Embase, Ovid and ProQuest. To evaluate the methodological quality of these studies, the Cochrane Risk of Bias (RoB 2.0) tool was applied. PBMT demonstrated consistent short-term reductions in pain intensity and improvements in QoL. Additional positive effects on sleep quality and psychological well-being were observed, indicating that PBMT may provide additional therapeutic benefits beyond pain reduction, including improvements in sleep quality and psychological well-being. PBMT has shown promise as a safe, non-pharmacological adjunct therapy that may provide short-term improvements in pain levels and QoL, but substantial heterogeneity limits generalizability. Clinical trials with large samples and standardized methodologies should be conducted to better clarify the role of PBMT in multidisciplinary therapy for FMS.", "url": "https://pubmed.ncbi.nlm.nih.gov/42334638/" }, { "pmid": "42327760", "title": "Elevated serum levels of interleukin-11 and matrix metalloproteinase-9 in myalgic encephalomyelitis/chronic fatigue syndrome.", "pub_date": "2026-06-22", "journal": "Frontiers in immunology", "authors": "Chinnappan, Baskaran, Kempuraj, Duraisamy, Aenlle, Kristina K, Middleton, Ashley et al.", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease of unknown etiology associated with chronic severe fatigue and neurological symptoms, including dizziness, sleep disturbances, cognitive impairment and pain. There are no reliable blood biomarkers available for ME/CFS, possibly due to the lack of specific pathogenesis, even though Epstein-Barr Virus (EBV) has been suspected. We quantified the levels of interleukin-11 (IL-11) in the serum of female ME/CFS patients (n = 40; mean age 51 years) and age- and gender-matched healthy control subjects (n = 38; mean age 43), as well as matrix metalloproteinase-9 (MMP-9) in ME/CFS patients (n = 18; mean age 57 years old) and healthy control subjects (n = 18; mean age 53 years old), using an enzyme-linked immunosorbent assay (ELISA). We hypothesized that mast cells (MC) stimulated by EBV may be involved. MC are unique tissue immune cells that have been implicated in ME/CFS. MC were grown from human umbilical cord blood CD34", "url": "https://pubmed.ncbi.nlm.nih.gov/42327760/" }, { "pmid": "42325052", "title": "Tryptophan Metabolism and Aryl-Hydrocarbon Receptor Agonists in the Gut Microbiome of People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.", "pub_date": "2026-06-22", "journal": "MicrobiologyOpen", "authors": "Esteban, David J, Conrad, Brynn, Cullinan, Autumn, Luong, Sharon et al.", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease with unknown biological basis and no cure. Microbiome dysbiosis has been reported in people with ME/CFS but its relevance to pathophysiology is unknown. Gut microbes are an important source of tryptophan metabolites that activate the aryl hydrocarbon receptor (AHR), a regulator of homeostatic and inflammatory genes. Dysregulated activation of AHR contributes to pathophysiology of several neuroimmune and chronic diseases but its role in ME/CFS has not been investigated. The purpose of this study was to investigate the production of tryptophan metabolites and AHR agonists by gut microbes of people with ME/CFS. We found lower diversity and altered microbiome community structure in people with ME/CFS and changes in the subcommunity of microbes that correlated with tryptophan metabolites. Using targeted metabolomics we identified nine metabolites elevated in the stool of people with ME/CFS, including three AHR agonists. Stool ex vivo cultures were tested for their capacity to activate AHR in a reporter cell line and by qPCR. AHR activation did not differ between people with ME/CFS and controls, however, we detected elevated agonist activity in people with neurocognitive symptoms, regardless of underlying disease. These findings are consistent with previous work revealing changes in the gut microbiome of people with ME/CFS and adds further support to alterations in tryptophan metabolism associated with the disease. Altered AHR activity by gut microbial metabolites may be a common mechanism contributing to neurocognitive symptoms in diseases including ME/CFS.", "url": "https://pubmed.ncbi.nlm.nih.gov/42325052/" }, { "pmid": "42322758", "title": "Study on Sijunzi decoction regulating intestinal microbiota structure and metabolic profile for improving chronic fatigue syndrome.", "pub_date": "2026-06-21", "journal": "Journal of chromatography. B, Analytical technologies in the biomedical and life sciences", "authors": "Shan, Yi, Jin, Jin, Wu, Yiduo, Yu, Runsheng et al.", "abstract": "Chronic fatigue syndrome (CFS) is a syndrome encompassing several systemic diseases. Sijunzi Decoction (SJZD) is a classic formula in traditional Chinese medicine (TCM) for the treatment of spleen deficiency syndrome. Studies have demonstrated that SJZD can effectively alleviate CFS by modulating the gut microbiota, yet the underlying mechanisms are still unknown. This investigation examined the specific mechanisms by which SJZD regulates intestinal microbiota structure and metabolic profiles to improve CFS. A rat model of CFS triggered by combined multi-factor stress was established, and the rats were treated with SJZD continuously for 30 days. Comprehensive evaluation included body weight, 3-h food intake, intestinal propulsion and gastric emptying rates, exhaustive swimming time, skeletal muscle ATPase content, and indices correlated with oxidative stress and energy metabolism. Serum metabolomics, fecal metabolomics, and 16S rRNA microbial community analysis were applied to investigate the therapeutic mechanism of SJZD in CFS rats. SJZD can improve the general symptoms of CFS rats, as well as the abnormalities of indicators related to oxidative stress and energy metabolism. Metabolomics results showed that SJZD exerted therapeutic effects mainly by regulating 7 fecal differential metabolites and 25 serum differential metabolites. 16S rRNA sequencing analysis illustrated that SJZD elevated the diversity and composition of intestinal microbiota in CFS rats, while decreasing the Firmicutes/Bacteroidetes (F/B) ratio. Moreover, significant relationships were detected between the microbiota and serum/fecal metabolites as well as biochemical indices. SJZD exhibited significant therapeutic effects on CFS rats, and its mechanism may be correlated with regulating the intestinal microbiota structure and metabolic profiles of CFS rats, thereby improving oxidative stress injury and energy metabolism disorders.", "url": "https://pubmed.ncbi.nlm.nih.gov/42322758/" }, { "pmid": "42321833", "title": "Gastrointestinal symptoms correlate with core clinical features and systemic inflammation in myalgic encephalomyelitis/chronic fatigue syndrome.", "pub_date": "2026-06-20", "journal": "Journal of translational medicine", "authors": "Brown, Mikayla, Vernon, Suzanne D, Indart, Alyssa C, Green, Peter H et al.", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness marked by fatigue, cognitive impairment, and post-exertional malaise. Gastrointestinal (GI) symptoms are frequently reported, yet their relationship to central features of the illness and biological correlates remains poorly understood. We aimed to characterize GI symptom burden in ME/CFS and evaluate its associations with core clinical features and specific immune and inflammatory markers, with attention to potential gut-related contributions to disease expression. GI symptoms and 49 additional symptoms across nine domains were assessed in 116 ME/CFS patients and 80 matched controls. Plasma C-reactive protein (CRP) and antibodies against dietary and microbial antigens were measured as indicators of systemic inflammation and putative gut-derived antigen exposure. ME/CFS patients reported significantly elevated GI symptom frequency and severity compared with controls, with 53% of ME/CFS patients versus 8% of controls reporting a prior diagnosis of irritable bowel syndrome. GI symptom burden correlated with fatigue, cognitive difficulties, flu-like symptoms, pain, sleep disturbances, neurological complaints, and sensory sensitivities, independent of illness duration. CRP levels were higher in patients with greater GI symptoms and correlated with GI, fatigue, musculoskeletal pain, and flu-like symptom burden. Patients with greater flu-like symptom expression exhibited higher IgM responses to dietary gliadin and bacterial lipopolysaccharide. These associations were not detected in controls. GI symptoms are a prominent, clinically relevant dimension of ME/CFS, associated with broader symptom burden and inflammatory heterogeneity. These findings highlight the relevance of gut-related and immune processes in ME/CFS and underscore the value of incorporating GI symptom assessment in translational studies to help refine mechanistic understanding and improve therapeutic stratification.", "url": "https://pubmed.ncbi.nlm.nih.gov/42321833/" }, { "pmid": "42320559", "title": "Systems neuroendocrinology in ME/CFS and long COVID: a chronobiological framework for hormone-based research.", "pub_date": "2026-06-20", "journal": "Frontiers in neuroendocrinology", "authors": "Thomas, Natalie, Huang, Katherine, Schneider-Futschik, Elena K, Pollack, Beth et al.", "abstract": "Hormonal dysregulation is increasingly reported in ME/CFS and Long COVID, yet the broader role of neuroendocrine disruption in these conditions remains underexplored. While changes in steroid, peptide, and neuropeptide hormones have been identified, these findings are often considered in isolation and without attention to their timing or integration within broader physiological systems. The hypothalamic-pituitary axes regulate endocrine, immune, autonomic, nervous, and metabolic functions, systems commonly affected in both conditions, yet their circadian and menstrual dynamics are rarely investigated. In this review, we examine the evidence for neuroendocrine dysfunction in ME/CFS and Long COVID, focusing on hormone output, functional assays, receptor expression, and the coordination of endocrine biorhythms. Sex hormone signalling emerges as a key area of vulnerability, particularly given the female predominance in both conditions and the complexity of reproductive hormone regulation. We argue that accurate hormone measurement and time-structured sampling, including circadian and menstrual rhythms, are essential for detecting meaningful biological differences. By embedding chronobiology-aware, dense-sampling strategies and integrating multi-omic analyses into multi-system study designs, we outline a framework for investigating dynamic endocrine mechanisms underlying symptom variability and multisystem dysfunction, which may ultimately support the development of more targeted, personalised interventions.", "url": "https://pubmed.ncbi.nlm.nih.gov/42320559/" }, { "pmid": "42313182", "title": "[Not Available].", "pub_date": "2026-06-18", "journal": "Der Nervenarzt", "authors": "Erbguth, F, Tegenthoff, M, Böwering-Möllenkamp, C, Schain, H et al.", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/42313182/" }, { "pmid": "42310705", "title": "Effectiveness of adapted physical activity and therapeutic exercise programme in improving chronic fatigue syndrome in long COVID, delivered via hospital-based rehabilitation versus telerehabilitation.", "pub_date": "2026-06-18", "journal": "Trials", "authors": "Kabir, Feroz, Yin, Khin Nyein, Jeffree, Mohammad Saffree, Ahmedy, Fatimah Binti et al.", "abstract": "Long COVID is a prevalent condition characterised by pain, fatigue, disability, and a multitude of health issues. There are various treatment options for managing long COVID symptoms, including non-pharmacological interventions like physiotherapy and rehabilitation, which can be effectively delivered either in institutional care settings or via telerehabilitation. This three-arm randomised controlled trial included 145 participants selected from a population-based cohort in eight administrative divisions in Bangladesh. Participants aged 18 and above diagnosed with chronic fatigue syndrome (CFS) secondary to long COVID were included and history of fatigue, cardiovascular, neuro-musculoskeletal, or respiratory diseases, or red flag signs were excluded. Participants were allocated to three groups: hospital-based rehabilitation (HBR), telerehabilitation (TR), or a home programme (HP). Interventions consisted of an individualised exercise programme. The HBR and TR groups received physiotherapist-supervised sessions with sessions lasting 45 min, twice weekly for 8 weeks. And the HP group performed exercises independently following structured instruction. Fatigue, the primary outcome, was measured using the Chalder fatigue scale, while secondary outcomes were quality of life measured using the 36-item Short Form Survey (SF-36), disability-adjusted life years (DALYs), and cardiorespiratory parameters (blood pressure, pulse rate, oxygen saturation, and lung capacity). Between 1st July 2023 and 31st December 2023, 145 participants were enrolled, with a mean age of 46.1 ± 6.7 years. After 8 weeks of intervention, the among-group within-group comparison showed a significant difference in fatigue level (HBR: P < 0.001; TR: P < 0.001; HP: P < 0.321), physical functioning (HBR: P < 0.001; TR: P < 0.001; HP: P < 0.057), and episodic disability (HBR; TR; HP: P < 0.001) among the participants when comparing them between the groups. In multiple comparisons, results showed that differences were observed in the Chalder fatigue scale, physical functioning, and episodic disability between all groups. Hospital-based rehabilitation showed a lower mean score compared to telerehabilitation (p < 0.0001) and the home programme (p < 0.0001). Additionally, telerehabilitation was significantly better than the home programme (p < 0.0001), indicating hospital-based rehabilitation's superior efficacy in reducing fatigue, improving physical function, and reducing disability. Physiotherapy as hands-on implementation in a hospital setting was substantially more effective than telerehabilitation. Training healthcare professionals to improve accessibility to rehabilitation would help mitigate the consequences of long COVID-19. The trial was registered with the clinical trial registry of India (CTRI/2023/03/050808. Registered on 17/03/2023).", "url": "https://pubmed.ncbi.nlm.nih.gov/42310705/" }, { "pmid": "42298601", "title": "Self-management support needs for individuals with Myalgic Encephalomyelitis and their next of kin - a qualitative study.", "pub_date": "2026-06-16", "journal": "BMC health services research", "authors": "Grønning, Kjersti, Lysfjord, Liv Eli, Røstad, Ann Katrin Hagen", "abstract": "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, disabling condition with limited evidence-based treatment options. Self-management support is recommended to improve people's coping and quality of life, yet little is known about whether the provided self-management support meet individuals with ME/CFS and their next of kins needs. The aim of this study was to explore the self-management support needs of individuals with ME/CFS and their next of kin, and to identify barriers and facilitators to effective self-management support in order to inform improvements to existing self-management interventions. We conducted an exploratory descriptive qualitative study using a combination of semi-structured individual and focus group interviews with a total of 16 participants (12 individuals with ME/CFS and four next of kin) in Norway. Data were analysed thematically within a constructivist framework. We identified three main themes. Theme one was named \"Individualised and accessible support\", focusing on the importance of timing, readiness, and flexible delivery formats (digital, hybrid, modular). The second theme was named \"Continuity and validation\", emphasising current gaps in follow-up care for individuals with ME/CFS and experiences of stigma. The third main theme was named \"The role of peer support and practical strategies\", highlighting the value of peer interaction, sharing experiences, and adaptive tools (e.g., pacing, symptom tracking). Overall, the participants described that existing self‑management support was poorly aligned with their physical and cognitive limitations, lacked consistent and structured follow‑up, and often conveyed contradictory guidance on activity management. Self-management support for individuals with ME/CFS should be integrated into standardised care pathways, delivered in phased and modular formats, and include structured follow-up. Digital and hybrid solutions can enhance accessibility. Including peer-led components and family involvement may foster empowerment and reduce isolation. Training healthcare professionals in ME-sensitive communication and developing national guidelines are critical to improving service quality and reducing stigma.", "url": "https://pubmed.ncbi.nlm.nih.gov/42298601/" }, { "pmid": "42291861", "title": "Approach to Fatigue in Primary Care: A Practical Diagnostic Framework for General Practitioners.", "pub_date": "2026-06-15", "journal": "Cureus", "authors": "Elbaroumi, Omar", "abstract": "Fatigue is one of the most common presenting complaints in primary care and poses a significant diagnostic challenge due to its multifactorial aetiology. While the majority of cases are benign and self-limiting, fatigue may also represent an early manifestation of serious underlying pathology. This review distinguishes between acute fatigue, typically transient and associated with intercurrent illness or lifestyle factors, and chronic fatigue, defined as fatigue persisting for six or more weeks, which is more likely to be multifactorial in origin. This narrative review aims to provide a practical and structured diagnostic framework for general practitioners to evaluate and manage fatigue effectively in the primary care setting. A narrative review of the literature was conducted using PubMed and Google Scholar. Searches were limited to articles published in English from 2010 onwards. Search terms included \"fatigue,\" \"primary care,\" \"chronic fatigue,\" \"myalgic encephalomyelitis,\" \"post-viral fatigue,\" \"sleep disorders,\" and \"functional somatic syndromes.\" Seminal references predating 2010 were retained where no suitable replacement was available. This review did not employ a formal systematic search strategy, and no risk-of-bias assessment was performed, consistent with the narrative review format. Fatigue arises from a wide range of physical, psychological, and lifestyle-related causes, best understood through a three-tier classification: primary/idiopathic, secondary, and psychosocial. A systematic approach incorporating thorough history-taking, focused clinical examination, and judicious use of investigations is essential. Identification of red flag symptoms is critical to exclude serious conditions, including malignancy and chronic infections. A structured, patient-centred approach enables general practitioners to manage fatigue effectively while minimising unnecessary investigations and ensuring timely identification of serious disease.", "url": "https://pubmed.ncbi.nlm.nih.gov/42291861/" }, { "pmid": "42289444", "title": "Fatigue-associated gut bacteria in Japanese healthy adults characterized by metagenomic analysis.", "pub_date": "2026-06-15", "journal": "Scientific reports", "authors": "Masuoka, Hiroaki, Miyatake, Takumi, Park, Jonguk, Negishi, Hiroki et al.", "abstract": "Emerging evidence suggests that fatigue caused by accumulated stress may serve as a prodromal symptom of psychiatric disorders, and gut microbiome dysbiosis has been reported in many such conditions. However, little is known about microbial and metabolic signatures associated with fatigue in otherwise healthy individuals. This study aimed to investigate associations between fatigue, the gut microbiome, and fecal metabolites in healthy Japanese adults. We identified characteristic microbial and metabolic differences specific to fatigued healthy individuals. Taxonomic analysis revealed a reduction in potentially beneficial bacteria and an enrichment of Escherichia coli in their gut microbiome. Functional profiling demonstrated enrichment of KEGG orthologs related to oxidative stress and depletion of energy-producing pathways. Correspondingly, key energy metabolites such as citrate were decreased. Notably, some fatigue-associated bacterial alterations overlapped with findings from external datasets on psychiatric disorders and myalgic encephalomyelitis/chronic fatigue syndrome, suggesting associative overlap in gut microbial alterations. These findings suggest associations between host fatigue and gut microbiome alterations involving oxidative stress and impaired energy metabolism. The consistent overlap of fatigue-associated microbial changes with those observed in psychiatric disorders highlights the potential relevance of gut microbial signatures in fatigue-related biological states. This study provides a foundation for future studies on gut microbial and metabolic pathways.", "url": "https://pubmed.ncbi.nlm.nih.gov/42289444/" }, { "pmid": "42286686", "title": "Two-timepoint multidomain follow-up of post-COVID condition and ME/CFS: overlapping autonomic, small-fiber, and cognitive changes.", "pub_date": "2026-06-13", "journal": "Journal of translational medicine", "authors": "Azcue, N, Barranco, C, Tijero-Merino, B, Acera, M et al.", "abstract": "Post-COVID condition (PCC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) show marked clinical overlap, suggesting a shared post-infectious pathophysiology. This study aims to characterize the longitudinal change of autonomic function, small-fiber integrity, cognitive performance, and clinical symptoms in PCC and ME/CFS, and to determine whether trajectories differ between diagnostic groups. Thirty-eight participants (21 PCC, 17 ME/CFS) underwent two standardized evaluations separated by a median of 31 months. Assessments included comprehensive autonomic testing, small-fiber evaluation, and an extensive neuropsychological battery. ME/CFS showed longer disease duration than PCC at baseline (median 42 vs. 12 months), while the interval between evaluations was comparable (31 vs. 30 months). Baseline profiles were largely overlapping, although ME/CFS showed nominally higher QST warm detection thresholds (p = 0.034), greater autonomic symptom burden (p = 0.038), and lower hemodynamic scores (p = 0.019), none surviving FDR correction. Cross-domain analyses linked small-fiber symptoms with autonomic symptom burden (Rho = 0.65, pFDR = 0.002) and fatigue (Rho = 0.55, pFDR = 0.018), while fatigue was negatively associated with processing speed (Rho = - 0.57, pFDR = 0.004), attention (Rho = - 0.49, pFDR = 0.018), and executive function (Rho = - 0.44, pFDR = 0.047). Rank-transformed mixed-effects models identified FDR-corrected Time effects, with increases in CHEPs (pFDR < 0.001) and verbal memory (pFDR = 0.010), and decreases in processing speed (pFDR = 0.006) and QST cold thresholds (pFDR = 0.038). PCC and ME/CFS showed broadly overlapping multidomain profiles, with particularly similar profiles at follow-up. This suggests that, among individuals with persistent symptoms, PCC may increasingly resemble longer-standing ME/CFS across autonomic, small-fiber/sensory, and cognitive domains. These findings are consistent with overlapping post-infectious mechanisms, but do not establish identical disease trajectories or definitive disease convergence.", "url": "https://pubmed.ncbi.nlm.nih.gov/42286686/" }, { "pmid": "42286685", "title": "Combatting ventilator induced diaphragm dysfunction with human bone marrow mesenchymal stromal cell-derived extracellular vesicles.", "pub_date": "2026-06-13", "journal": "Skeletal muscle", "authors": "Wen, Ya, Zhang, Xiang, Hedström, Yvette, Cacciani, Nicola et al.", "abstract": "Prolonged mechanical ventilation is closely associated with ventilator-induced lung injury (VILI) and ventilator-induced diaphragm dysfunction (VIDD). These two conditions occur in parallel and contribute to delayed weaning, prolonged intensive care unit (ICU) stay, and poor clinical outcomes. This study evaluated whether human BM-MSC-derived extracellular vesicles (EVs) can simultaneously alleviate lung and diaphragm abnormalities in a unique rat experimental ICU (ExICU) model. Rats were subjected to 5 days of controlled mechanical ventilation with or without a single intravenous EV dose. Outcomes included lung histopathology, diaphragm single-fiber contractile function, transcriptomics and metabolomics of diaphragm muscle, proteomics and metabolomics of lung tissue, and serial proteomics of bronchoalveolar lavage fluid (BALF). Five days of mechanical ventilation in the ExICU model were accompanied by severe lung morphological damage and approximately 50% reductions in diaphragm fiber size and specific force. EV treatment was associated with parallel improvements in lung pathology and diaphragm function. Multi-omics revealed coordinated molecular disturbances across lung, BALF, and diaphragm after mechanical ventilation, the majority of which were reversed by EVs. Our findings demonstrate an association between lung injury and diaphragm dysfunction during prolonged mechanical ventilation. BM-MSC-derived EVs exert parallel protective effects on both organs and represent a promising intervention to reduce complications of mechanical ventilation in critically ill patients.", "url": "https://pubmed.ncbi.nlm.nih.gov/42286685/" }, { "pmid": "42284918", "title": "UHPLC-Q-Exactive Orbitrap MS-based brain-gut metabolomics implicates multi-pathway modulation by Ginseng stem-leaf saponins in chronic fatigue syndrome mice.", "pub_date": "2026-06-13", "journal": "Journal of pharmaceutical and biomedical analysis", "authors": "Wu, Wei, Aishan, Saibire, Zhang, Meng, Chen, Xue et al.", "abstract": "Ginseng stem-leaf saponins (GSLS) were evaluated as potential bioactive food ingredients by characterizing brain-gut metabolic disturbances in a chronic fatigue syndrome (CFS) mouse model and assessing the regulatory effects of GSLS using ultra-high-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS). Male C57BL/6 mice were assigned to control, model, positive control, and GSLS groups (n = 6). A long-term forced-swimming induction protocol was used to establish fatigue-like phenotypes, and fecal and brain tissue samples were collected for untargeted metabolomics with multivariate and pathway analyses. Seventeen differential metabolites were identified in brain tissue and 17 in fecal samples in association with model induction and GSLS supplementation. The altered pathways were mainly related to lipid-derived mediators and membrane-lipid remodeling, including arachidonic acid metabolism, steroid biosynthesis, glycerophospholipid metabolism, ether lipid metabolism, and primary bile acid biosynthesis, with additional involvement of energy- and redox-relevant cofactor/vitamin metabolism, such as pantothenate and CoA biosynthesis, folate-mediated one-carbon metabolism, and lipoic acid metabolism. GSLS partly normalized fatigue-like brain and fecal metabolic abnormalities, suggesting potential links to brain-gut axis regulation involving neurotransmitter-related metabolism, hypothalamic-pituitary-adrenal (HPA)-axis-associated steroid metabolism, inflammation, and oxidative stress. These findings support GSLS as a promising bioactive ingredient for maintaining vitality and metabolic resilience in functional food applications.", "url": "https://pubmed.ncbi.nlm.nih.gov/42284918/" }, { "pmid": "42279648", "title": "The Potential Role of Camel Milk in Alleviating Chronic Fatigue Syndrome in Mice: A Network Pharmacology and In Vivo Validation Study.", "pub_date": "2026-06-12", "journal": "Foods (Basel, Switzerland)", "authors": "Li, Hongman, Osman, Henigul, Zhang, Hongyan, Chen, He et al.", "abstract": "Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex and debilitating disorder with limited treatment options. Camel milk (CM), known for its rich nutrients and anti-fatigue properties, may offer multi-target benefits for managing this condition. This study utilized an integrated approach combining metabolomics, network pharmacology, and animal experiments. CM metabolites were profiled and screened via ADME. Potential targets were predicted and intersected with CFS/ME-associated genes. Male BALB/c mice were subjected to chronic restraint and forced swimming to evaluate the effects of CM (1000 mg/kg) on behavioral, inflammatory, neuroendocrine, and metabolic parameters. CM administration significantly improved exhaustive swimming time and reduced immobility. It attenuated systemic inflammation (restored IL-10), normalized brain CREB and", "url": "https://pubmed.ncbi.nlm.nih.gov/42279648/" }, { "pmid": "42278463", "title": "Raman Spectroscopy Combined with Machine Learning Reveals Myalgic Encephalomyelitis-Associated Biomolecular Signatures at Rest and After Standardized Stress.", "pub_date": "2026-06-12", "journal": "International journal of molecular sciences", "authors": "Heidarifard, Maryam, Moezzi, Atefeh, Dallaire, Frédérick, Ember, Katherine et al.", "abstract": "Myalgic encephalomyelitis (ME) is characterized by profound fatigue, post-exertional malaise (PEM), and cognitive dysfunction. Despite its clinical significance, the pathophysiology of PEM and disease heterogeneity remain unclear, and no validated biomarkers are available for rapid diagnosis or monitoring. We aimed to develop a screening approach combining label-free Raman spectroscopy (RS) and machine learning modeling (ML) to detect biomolecular changes in blood plasma and differentiate patients with ME from sedentary healthy controls. Blood plasma was collected from 115 patients with ME and 45 controls at rest (T0) and 90 min after a standardized, non-invasive stress test designed to induce PEM. Plasma samples were analyzed by RS, and ML models were developed independently at each time point to differentiate patients with ME and controls. The RS-ML models identified spectral features consistent with contributions from proteins, lipids, and low-molecular-weight metabolites. At T0 and T90, the area under the receiver operating characteristic curve, accuracy, specificity and sensitivity were 0.85 and 0.83, 79% and 84%, 82% and 90%, and 73% and 69%, respectively. RS-ML provides a rapid, low-cost approach to detect ME-associated biomolecular signatures in plasma and capture biochemical alterations associated with standardized stress.", "url": "https://pubmed.ncbi.nlm.nih.gov/42278463/" }, { "pmid": "42278300", "title": "Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis.", "pub_date": "2026-06-12", "journal": "International journal of molecular sciences", "authors": "Souma, Bernard, Elremaly, Wesam, Akoume, Marie-Yvonne, Elbakry, Mohamed et al.", "abstract": "Myalgic Encephalomyelitis (ME) is a chronic, multisystem disease characterized by systemic metabolic dysfunction and post-exertional malaise (PEM). In this study, we investigated the dysregulation of irisin, an exercise-induced myokine, and its potential antagonism by thrombospondin-1 (TSP-1). In a cross-sectional study (92 ME patients vs. 44 sedentary healthy controls), plasma irisin and TSP-1 levels were measured at baseline and after a 90 min mechanical stress challenge applied to induce PEM. ME patients exhibited significantly lower baseline irisin (", "url": "https://pubmed.ncbi.nlm.nih.gov/42278300/" }, { "pmid": "42277526", "title": "[Pain in post-acute infection syndromes: clinical classification and practical management].", "pub_date": "2026-06-12", "journal": "MMW Fortschritte der Medizin", "authors": "Luchting, Benjamin", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/42277526/" }, { "pmid": "42277311", "title": "Significant aggravation of pre-existing myalgic encephalomyelitis/chronic fatigue syndrome following proton beam therapy for sphenoid wing meningioma: case report.", "pub_date": "2026-06-12", "journal": "Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]", "authors": "Fischer, Christian, Seidlitz, Annekatrin, Krause, Mechthild", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disorder characterized by profound fatigue, post-exertional malaise (PEM), immune dysregulation, and mitochondrial dysfunction. While radiation exposure has been linked to fatigue syndromes with overlapping pathophysiology, no previous reports have described the effects of therapeutic radiation, including proton beam radiotherapy (PBRT), in patients with ME/CFS. We report the case of a 46-year-old woman with a pre-existing, clinically confirmed diagnosis of ME/CFS (Bell score 60, ECOG 1), who underwent postoperative PBRT (50.4 Gy in 28 fractions) for a recurrent left sphenoid wing meningioma (CNS WHO grade 1). The tumor had been surgically resected but showed residual disease with early postoperative progression and close proximity to the left optic nerve, prompting the indication for adjuvant radiotherapy. The patient initially tolerated treatment well, with only mild acute worsening of pre-existing fatigue and transient corticosteroid-responsive symptoms. However, within weeks of completing radiotherapy, she developed progressive and severe worsening of fatigue, myalgia, vertigo, and hypersensitivity to sensory stimuli as well as cognitive decline. Over several months, she became completely bedridden (Bell score 0, ECOG 4) with persistent ME/CFS aggravation unresponsive to supportive measures persisting until the last known contact 20 months after radiation. Follow-up imaging showed stable postoperative findings without tumor progression or new structural brain lesions. This case illustrates a profound and irreversible deterioration of ME/CFS following PBRT, suggesting that radiation-induced mitochondrial dysfunction, oxidative stress, and chronic inflammatory activation may critically worsen pre-existing metabolic fragility. Despite the theoretical advantages of proton radiotherapy in reducing normal tissue exposure, its protective effects may be insufficient in patients with baseline mitochondrial malfunction. This is, to our knowledge, the first reported case of severe and sustained ME/CFS exacerbation after radiotherapy. The case emphasizes the urgent need for risk stratification, tailored consent processes, and research in the field of radiotherapy tolerance in ME/CFS patients, as conventional expectations regarding side effects may not predict outcomes in this vulnerable population.", "url": "https://pubmed.ncbi.nlm.nih.gov/42277311/" }, { "pmid": "42276999", "title": "Benchmarking large language models for cell-free RNA diagnostic biomarker discovery.", "pub_date": "2026-06-12", "journal": "Nature communications", "authors": "Gaudio, Hunter A, Bliss, Andrew, Loy, Conor J, Eweis-LaBolle, Daniel et al.", "abstract": "Large language models can synthesize biomedical knowledge, parse vast amounts of data, and generate code, positioning them as promising tools for biomarker discovery from high-throughput omics data. Here, we benchmark six models from OpenAI, Anthropic, and Google on plasma cell-free RNA datasets spanning three clinical cohorts: Kawasaki disease versus multisystem inflammatory syndrome in children, active tuberculosis versus symptomatic respiratory controls, and myalgic encephalomyelitis/chronic fatigue syndrome versus sedentary controls. We evaluate literature-guided nomination of diagnostic gene panels for downstream machine learning and autonomous construction of end-to-end classifiers from raw count matrices to held-out test predictions. Despite prompt adherence issues, model-nominated panels recapitulate canonical immune pathways and outperform random panels across cohorts, even matching differential gene expression baselines in the tuberculosis cohort. End-to-end automation proves feasible but is model- and task-dependent. One model approaches conventional performance for Kawasaki disease versus multisystem inflammatory syndrome in children, whereas performance decreases for tuberculosis and myalgic encephalomyelitis/chronic fatigue syndrome cohorts. These findings delineate current capabilities and limitations of large language models in diagnostics and open a path for their future use in biomarker discovery.", "url": "https://pubmed.ncbi.nlm.nih.gov/42276999/" }, { "pmid": "42274123", "title": "Dynamic microclot profiling: thromboelastography advances precision management in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.", "pub_date": "2026-06-11", "journal": "Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis", "authors": "Saleem, Shafaq, Hussain, Ahmad, Haroon, Muhammad, Raza, Ahmad et al.", "abstract": "Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) share overlapping symptoms, and emerging evidence implicates persistent fibrinoid microclots in their pathophysiology, contributing to impaired microcirculation. This review explores the role of microclots and evaluates thromboelastography (TEG) as a potential diagnostic tool. A comprehensive literature review was conducted using major biomedical databases. Studies indicate microclots are prevalent in both conditions. Long COVID patients demonstrate a TEG profile of increased clot strength (maximum amplitude) and reduced fibrinolysis (LY30), suggesting a persistent hypercoagulable state. Despite its advantages in real-time assessment, TEG interpretation faces challenges from preanalytical variability and a lack of standardized protocols. Promising therapeutic trials, including anticoagulants (e.g., apixaban) and fibrinolytics (e.g., lumbrokinase), require further validation. Technological advancements like AI-driven TEG analysis and portable devices could improve diagnostic precision. In conclusion, persistent microclots are a key pathophysiological feature. TEG provides a promising, novel approach for detecting coagulation abnormalities and could guide treatment, but requires standardization in future clinical trials. Future research should integrate multiomics biomarkers for precision therapeutics to improve patient outcomes.", "url": "https://pubmed.ncbi.nlm.nih.gov/42274123/" }, { "pmid": "42261335", "title": "A new patient-led approach to building research infrastructure and evidence generation.", "pub_date": "2026-06-09", "journal": "Oxford open immunology", "authors": "Cousins, Oonagh, Leeming, Harry, Putrino, David, Gordon, Janna", "abstract": "Over recent decades, patient and public involvement (PPI) has become a more established element of health research policy, although its implementation is often criticized for tokenism and for underrepresenting marginalized groups. In fields such as complex chronic illness (CCI), where formal research activity has historically been limited, conventional PPI frameworks have had little scope for meaningful application. Within this context, a new wave of patient-led initiatives has emerged that moves beyond participation in existing systems toward the creation of independent infrastructures for knowledge generation, extending the principle of \"nothing about us, without us.\" This commentary examines Visible, a patient-founded health technology platform that combines daily energy-management tools with research infrastructure for CCIs. This infrastructure enables in-house data analyses and external collaborations, including app-based data studies, investigator-led research, and integration within clinical trials. We explore the advantages of this dual-purpose model, including greater inclusivity, sustained engagement, and richer longitudinal data. We also describe how embedding research functions within tools that patients find directly useful allows evidence generation and patient support to be mutually reinforcing.", "url": "https://pubmed.ncbi.nlm.nih.gov/42261335/" }, { "pmid": "42249466", "title": "Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study.", "pub_date": "2026-06-06", "journal": "Journal of translational medicine", "authors": "Kim, Laura, Cammà, Guido, Peters, Claudia Kedor, Mantwill, Maron et al.", "abstract": "Hyperbaric oxygen therapy (HBOT) has been proposed as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but evidence remains limited. This study evaluated its clinical effectiveness and feasibility, as well as associated functional brain changes. Thirty patients with ME/CFS (mean age 42.3 ± 11.7 years; 7 males, 23 females) received 40 HBOT sessions. Clinical outcomes were assessed at baseline, during treatment, and four weeks post-treatment. The primary outcome was change in the physical functioning subscale of the Short Form-36 Health Survey (SF-36 PF). Secondary outcomes included severity of core symptoms assessed via questionnaires, exercise capacity, handgrip strength, cognitive performance, orthostatic intolerance, and brain magnetic resonance imaging (MRI; volumetry and functional connectivity [FC]). Thirty age- and sex-matched healthy controls (mean age 42.3 ± 11.3 years; 7 males, 23 females) were included for MRI comparison. SF-36 PF significantly improved during HBOT compared with baseline (g = 0.71, p = 0.006). SF-36 pain (p = 0.002, g = 0.79) and Chalder Fatigue Scale also showed clinically meaningful reductions (p < 0.001, g = -0.87). Exercise capacity (g = 0.66), muscle strength (g = 0.40), and information processing speed (g = 0.52) improved significantly after treatment (all p < 0.05). Treatment adherence was high and tolerability was favorable, with no major adverse events reported. Functional MRI analyses revealed increased thalamic FC in ME/CFS patients compared to healthy controls in bilateral sensorimotor (p < 0.001, t = 5.65, FDR-corrected) and visuo-occipital regions (p < 0.001, t = 5.40, FDR-corrected) at baseline. Following HBOT, thalamic hyperconnectivity shifted toward patterns observed in healthy controls. Responders, defined as a ≥ 10 points increase in SF-36 PF, showed greater reductions in thalamic hyperconnectivity than non-responders (p < 0.001, t = -4.34 to -5.18, FDR-corrected). HBOT was well tolerated and associated with significant improvements in physical functioning, fatigue, pain, and cognitive performance in ME/CFS. The post-treatment shift in thalamocortical connectivity toward healthy control patterns and its association with clinical response support the hypothesis that functional thalamic dysregulation contributes to ME/CFS pathophysiology and may be modulated by HBOT. This provides a network-level rationale for controlled trials to confirm therapeutic efficacy. ClinicalTrials.gov NCT06118138. Registered 01 November 2023 - Retrospectively registered, https://clinicaltrials.gov/study/NCT06118138?cond=ME%2FCFSamp;term=HBOTamp;rank=1 .", "url": "https://pubmed.ncbi.nlm.nih.gov/42249466/" }, { "pmid": "42249231", "title": "Novel activity and participation scales for children, adolescents, and young adults with postacute infection and vaccination syndromes and/or ME/CFS.", "pub_date": "2026-06-06", "journal": "European journal of pediatrics", "authors": "Weidmann, Carola, Grabbe, Annika, Eberhartinger, Maria, Kircher, Alissa et al.", "abstract": "Children, adolescents, and young adults (CYP) with postacute infection and vaccination syndromes (PAIVS), and/or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), experience profound loss in activity and participation. We introduce and psychometrically validate two new brief, age-adapted, and domain-specific questionnaires for clinical use assessing activity and participation in this vulnerable patient group. For this, 91 patients (aged 10-25 years) were assessed at the Munich Chronic Fatigue Center (MCFC) from 12/2022 to 11/2024. We designed the MCFC Activity Scale and MCFC Participation Scale and assessed construct validity using confirmatory factor analysis for both questionnaires. Reliability was evaluated via Cronbach's α. Factor-based MCFC Activity and Participation Scores (0-100) were derived and correlated with Bell Score, FSS, DSQ-PEM, and SF-12 Component Summary Scales (PCS and MCS). Discrimination for ME/CFS was evaluated using ROC analyses. Participants (mean age 15.6 ± 2.4 years) were predominantly female (64%). 65% were diagnosed with ME/CFS. The MCFC Activity Scale showed excellent one-factor fit (comparative fit index, CFI = 1.00) and good internal consistency (α = 0.82). The MCFC Participation Scale showed good internal consistency (α = 0.85) and acceptable one-factor fit (CFI = 0.817). Factor-based activity and participation were strongly correlated yet distinct (r = 0.73). Derived MCFC Activity and Participation Scores differed significantly by ME/CFS diagnosis (p ≤ 0.009). Scores correlated with Bell Score, FSS, DSQ-PEM, and SF-12 PCS (all p ≤ .002). For ME/CFS discrimination, the Activity Score achieved an AUC = 0.78 and the Participation Score an AUC = 0.72.Conclusion: The Activity Scale demonstrated strong construct validity. The Participation Scale showed good internal consistency. Both scores demonstrated good convergent validity with established patient-reported outcome measures, supporting clinical utility. They may serve as pragmatic screening tools for this vulnerable patient group.", "url": "https://pubmed.ncbi.nlm.nih.gov/42249231/" }, { "pmid": "42239825", "title": "The expanding potential of low-dose naltrexone in clinical practice with a focus on long COVID.", "pub_date": "2026-06-04", "journal": "The mental health clinician", "authors": "Pucci, Sara L, Veide, Allison, Pierce, Haley, Kaminski, Dana", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/42239825/" }, { "pmid": "42227214", "title": "Correction to \"Evidence of White Matter Neuroinflammation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Diffusion-Based Neuroinflammation Imaging Study\".", "pub_date": "2026-06-02", "journal": "Human brain mapping", "authors": "Authors not listed", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/42227214/" }, { "pmid": "42223876", "title": "[Transdisciplinary Expert Statement: care guide for people severely affected by ME/CFS in home-based care].", "pub_date": "2026-06-01", "journal": "Wiener medizinische Wochenschrift (1946)", "authors": "Hermisson, Joachim, Schreiner, Claudia, Weichselbaumer, Stefanie, Werner, Marlene et al.", "abstract": "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. The objective of this guide is to structure care measures in a way that prevents overexertion and promotes stability. 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. 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. HINTERGRUND: Viele Betroffene von Myalgischer Enzephalomyelitis/Chronischem Fatigue-Syndrom (ME/CFS) sind hochgradig pflegebedürftig. Gleichzeitig bedingt die Post-Exertionelle Malaise (PEM), das Kernmerkmal von ME/CFS, dass bereits geringe körperliche, orthostatische, kognitive oder sensorische Belastungen eine disproportionale Zustandsverschlechterung auslösen können. Dadurch ergeben sich spezifische Anforderungen und erhebliche Herausforderungen in der häuslichen Versorgung. Die pflegerische Versorgung wird bislang überwiegend von Angehörigen getragen, die dabei nur unzureichend Hilfe und Unterstützung finden. Gleichzeitig bestehen erhebliche Defizite in Wissen, Versorgungsstrukturen und professioneller Orientierung für die an der Betreuung beteiligten Pflege- und Gesundheitsberufe sowie Ärzt:innen. ZIEL: Ziel dieses Leitfadens ist es, pflegerische Maßnahmen so auszurichten, dass Überlastungen vermieden und Stabilität unterstützt wird. Der Leitfaden basiert auf einer Zusammenstellung praxisorientierter Maßnahmen, die sich aus Sicht von Betroffenen und pflegenden Angehörigen bewährt haben. Diese wurden durch Expert:innen aus Pflegewissenschaft, Physiotherapie, Allgemeinmedizin und Public Health fachlich eingeordnet und inhaltlich weiterentwickelt. Der Leitfaden beschreibt Anpassungen zentraler Pflegedimensionen – von Ernährung und Körperpflege bis hin zu Kommunikation und Umgang mit emotionalen Belastungen – an krankheitsspezifische Belastungsgrenzen. Ergänzend werden Anforderungen an die Pflegebeziehung und die Planung von Hausbesuchen dargestellt sowie Möglichkeiten palliativer Pflegeprinzipien diskutiert.", "url": "https://pubmed.ncbi.nlm.nih.gov/42223876/" }, { "pmid": "42222634", "title": "Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Leading to Assisted Suicide in a Patient in Her Late 30s: A Case Report.", "pub_date": "2026-06-01", "journal": "Cureus", "authors": "Opala, Dominika, Villiger, Erich, Levenfus, Ian", "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.", "url": "https://pubmed.ncbi.nlm.nih.gov/42222634/" }, { "pmid": "42220511", "title": "Immune remodeling and metabolic reprogramming in chronic fatigue: insights into GPCR signaling and epigenetic regulation.", "pub_date": "2026-06-01", "journal": "Frontiers in immunology", "authors": "Hu, Zekai, Wang, Jinyan, Ma, Sicong, Zhuang, Jie et al.", "abstract": "Inflammation-driven fatigue is a clinically significant feature of several chronic inflammatory conditions, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), post-COVID condition, autoimmune disease, and cancer-related fatigue. Across these conditions, partially overlapping disturbances in immune regulation, cellular metabolism, and neuroimmune signaling may contribute to persistent fatigue, despite important differences in initiating context and biological substrate. Current evidence implicates mitochondrial dysfunction, altered glycolysis and fatty acid utilization, lactate- and succinate-associated signaling, metabolite-sensing G protein-coupled receptor (GPCR) pathways, epigenetic acylation, and immune remodeling in the maintenance of fatigue. This narrative review synthesizes both shared and disease-context-specific mechanisms underlying inflammation-associated fatigue, with particular emphasis on immunometabolism, peripheral-central neuroimmune crosstalk, metabolite-GPCR signaling, and epigenetic regulation. We highlight GPCR signaling as a potentially important regulatory interface in inflammatory and metabolic pathways relevant to fatigue, while recognizing that direct causal evidence in human fatigue syndromes remains limited. The review also examines how metabolite-mediated epigenetic acylation may influence immune cell function and fatigue-related biology, although this association remains incompletely validated in fatigue-specific settings. By integrating metabolic dysregulation, neuroimmune signaling, and immune dysfunction, this review consolidates current knowledge on candidate biomarkers, mechanistic pathways, and emerging therapeutic targets in chronic inflammation-driven fatigue. Overall, this review provides a multidimensional framework for understanding fatigue across inflammatory disorders and for guiding future mechanistic and translational research.", "url": "https://pubmed.ncbi.nlm.nih.gov/42220511/" }, { "pmid": "42219745", "title": "Components and Delivery Formats of Cognitive Behavioral Therapy for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review and Component Network Meta-Analysis.", "pub_date": "2026-06-01", "journal": "Brain and behavior", "authors": "Wang, Shoujian, Ren, Jun, Fang, Sitong, Hao, Qiukui et al.", "abstract": "Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating condition characterized by persistent fatigue, impaired functioning, and substantial societal burden. Although cognitive behavioral therapy (CBT) is commonly used for CFS/ME, the effective components and delivery formats remain unclear. We systematically searched MEDLINE, Embase, PsyclNFO, Web of Science, the Cochrane Library, and major English and Chinese databases from inception to January 15, 2025, without language restrictions. Ultimately, a frequentist network meta-analysis (NMA) and component network meta-analysis (cNMA) of 16 randomized controlled trials were conducted to assess the associations between CBT components, delivery formats, and patient-important outcomes. At the treatment level, guided self-help CBT (mean difference [MD], -6.89; 95% CI, -9.56 to -4.22; moderate certainty) and individual CBT (MD, -4.81; 95% CI, -6.98 to -2.65; moderate certainty) probably reduced fatigue when measured immediately after treatment. At the component level, goal setting (incremental mean difference [iMD], -8.83; 95% CI, -16.92 to -0.74), third-wave components (iMD, -6.02; 95% CI, -11.33 to -0.72), and cognitive restructuring (iMD, -4.41; 95% CI, -8.83 to 0.01) were associated with reduced fatigue when measured immediately after treatment. Psychoeducation was potentially counterproductive (iMD, 5.23; 95% CI, 0.64 to 9.82). At the end of follow-up, cognitive restructuring was associated with reduced fatigue and depression, and improved physical function; goal setting was also associated with improved physical function. The combination of goal setting, third-wave components, and cognitive restructuring delivered via guided self-help may be an efficacious component-based intervention relative to the nonspecific treatment component (iMD, -16.33; 95% CI, -26.68 to -5.99). The effective CBT combination probably involves goal setting, third-wave components, and cognitive restructuring delivered via guided self-help, while psychoeducation may be detrimental. Future studies should prospectively examine core CBT components and their interactions, as well as incorporate measures of dose and intensity to guide more personalized and scalable interventions. CRD420251018083.", "url": "https://pubmed.ncbi.nlm.nih.gov/42219745/" }, { "pmid": "42212259", "title": "Cardiopulmonary exercise test results do not change over two sequential days in patients with chronic fatigue syndrome.", "pub_date": "2026-05-29", "journal": "Frontiers in physiology", "authors": "Mancini, Donna M, Cook, Dane B, Brunjes, Danielle L, Soto, Tiffany et al.", "abstract": "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 (VO 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/m For ME/CFS and CON subjects, there were no significant changes in Peak VO 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.", "url": "https://pubmed.ncbi.nlm.nih.gov/42212259/" }, { "pmid": "42205163", "title": "Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.", "pub_date": "2026-05-28", "journal": "Brain communications", "authors": "Aregawi, Lillian, Walitt, Brian, Sullivan, Patti, Norato, Gina et al.", "abstract": "Fatigue, brain fog and post-exertional malaise are major features of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of severe acute respiratory syndrome coronavirus 2. To date, no specific neurotransmitter abnormalities have been found in either condition. We examined the possibility of central catecholaminergic involvement and clinical correlates in post-infectious myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 groups compared to healthy volunteers and, as positive controls, Parkinson's disease patients. In an observational, cross-sectional cohort study conducted at the National Institutes of Health Clinical Center we measured CSF levels of catecholamines and metabolites in the four groups and assessed correlations with neurobehavioral measures. CSF indices of the central Norepinephrine Pathway (norepinephrine + 3,4-dihydroxyphenylglycol + 3-methoxy-4-hydroxyphenylglycol) and Dopamine Pathway (dopamine + 3,4-dihydroxyphenylacetic acid + homovanillic acid) were measured and related to patient-recorded outcomes and physiological assessments. Mean values for Norepinephrine Pathway activity (in pmol/mL) were lower in the post-infectious myalgic encephalomyelitis/chronic fatigue syndrome, post-acute sequelae of severe acute respiratory syndrome coronavirus 2, and Parkinson's disease groups compared to the healthy volunteer cohort (post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (-15.9, 95% confidence interval [-26.1, -5.7],", "url": "https://pubmed.ncbi.nlm.nih.gov/42205163/" }, { "pmid": "42196466", "title": "Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID.", "pub_date": "2026-05-27", "journal": "International journal of molecular sciences", "authors": "Petrov, Steliyan, Bozhkova, Martina, Ivanovska, Mariya, Kalfova, Teodora et al.", "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.", "url": "https://pubmed.ncbi.nlm.nih.gov/42196466/" }, { "pmid": "42196410", "title": "Toward a Molecular Reclassification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Integrating Multi-Omics, Machine Learning, and Precision Medicine.", "pub_date": "2026-05-27", "journal": "International journal of molecular sciences", "authors": "Frank, Joshua, Nesterovitch, Nicole, Movva, Chetana, Klimas, Nancy G et al.", "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.", "url": "https://pubmed.ncbi.nlm.nih.gov/42196410/" }, { "pmid": "42196290", "title": "Human Endogenous Retroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Roles in Pathogenesis, Immunity, Biomarkers and Therapeutics.", "pub_date": "2026-05-27", "journal": "International journal of molecular sciences", "authors": "Perera, Krishani Dinali, Oltra, Elisa, Carding, Simon R", "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.", "url": "https://pubmed.ncbi.nlm.nih.gov/42196290/" }, { "pmid": "42190845", "title": "Shared genetic risk between functional somatic syndromes, internalizing disorders, and immune-mediated diseases: a twin-sibling study.", "pub_date": "2026-05-27", "journal": "Brain, behavior, and immunity", "authors": "Steen, Olivier D, Ohlsson, Henrik, van Ockenburg, Sonja L, Kendler, Kenneth S et al.", "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.", "url": "https://pubmed.ncbi.nlm.nih.gov/42190845/" }, { "pmid": "42177403", "title": "Deficient TRPM3-linked mitochondrial Ca", "pub_date": "2026-05-24", "journal": "BMC immunology", "authors": "Magawa, Chandi Tabeth, Eaton-Fitch, Natalie, Muraki, Katsuhiko, Marshall-Gradisnik, Sonya", "abstract": "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 Ca Fluorescence live-cell imaging was used to investigate Ca Cytosolic Ca The results demonstrate that altered TRPM3-mediated cytosolic Ca", "url": "https://pubmed.ncbi.nlm.nih.gov/42177403/" }, { "pmid": "42175450", "title": "Post COVID-19 treated with AstraZeneca vaccine exacerbates arthritis with susceptibility to herpes in an older woman: A case report.", "pub_date": "2026-05-23", "journal": "Medicine", "authors": "Guzman, David Calderon, Brizuela, Norma Osnaya, Herrera, Maribel Ortiz, Peraza, Armando Valenzuela et al.", "abstract": "Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder that has seriously affected human health worldwide. This report describes a rare case of herpes infection, secondary to RA, that emerged after coronavirus disease 2019 (COVID-19) infection or vaccination. Despite pharmacological intervention for arthritis, herpes, and mental health symptoms, the patient's condition has not improved. A 70-year-old female homemaker, weighing 110 lbs, sought urgent care for persistent dysphoric mood and irritability attributed to a post-COVID infection. The ill-health condition set in with severe pain, followed shortly by the onset of herpetic lesions. She experienced the symptoms while suffering from chronic fatigue syndrome. A diagnosis of arthritis was made at the age of 60, and the patient has since been under treatment with analgesic therapy and prednisone. However, her doctor advised lowering the dose of her RA medications. At the age of 67, she developed herpes. She is currently on acyclovir and remains fully compliant with her medication. A simple skull magnetic resonance study depicted the absence of intracranial abnormality. Electromyography of normal muscles is silent at rest, without neuropathy. Cholesterol, sodium, chlorine, erythrocyte, and eosinophil were at the lower limit of normal, while lipase, phosphatase alkaline, and platelets were at the upper limit. An integrative approach was taken, combining pharmaceutical prescriptions for arthritis, herpes, and mood symptoms with unconventional complementary therapies. Oral food intake was initiated and well-tolerated; however, the patient's clinical condition did not improve with the current treatment. She is currently recovering at home on a regimen of vitamins, acyclovir, and analgesics. While she has shown clinical improvement, some complications have emerged. Diagnostic findings demonstrate that her health is not within normal limits, necessitating a daily regimen of prednisone, analgesic therapy, and hydroxyzine/losartan. This case highlights the importance of studying patients with RA. Risk factors for severe COVID-19 outcomes include older age and comorbidities. This case highlights the potential for COVID-19 infection or immunization to precipitate a flare of preexisting arthritis, causing severe lower limb manifestations and sacroiliitis (low back pain/sciatica) in older individuals receiving management for rheumatic disease. Immune abnormalities in patients treated with prednisone are elements in deciding the prescription and duration of this drug, and a neurological assessment is essential.", "url": "https://pubmed.ncbi.nlm.nih.gov/42175450/" }, { "pmid": "42174645", "title": "A systematic scoping review and conceptual analysis of new-onset fibromyalgia manifestations after non-hospitalized COVID-19: empirics, definitions, methodologies, pathophysiology, mapping of literature, and knowledge gaps.", "pub_date": "2026-05-23", "journal": "Journal of translational medicine", "authors": "Plaut, Shiloh", "abstract": "The global coronavirus pandemic has led to a quiet wave of a chronic illness referred to as 'Long/Post Covid-19 syndrome' (LC) which bears a notable resemblance to functional-somatic or 'fibromyalgia-type' syndromes, and whose pathophysiology is undetermined. The lack of effective therapies for LC is straining healthcare systems worldwide and causing widespread public health and socioeconomic concerns. \"Fibromyalgia\" is a controversial chronic pain condition of unknown etiology largely attributed to generalized sensory hypersensitivity due to dysregulated central pain processing pathways (i.e. neuroplasting central sensitization). Despite intense research and growing attention in the scientific community, the clinical overlap of fibromyalgia, somatic symptom disorder, and post-viral chronic fatigue, is a medical puzzle yet to be solved, especially when occurring in non-severe infections and previously healthy individuals. This systematic scoping review covers the empirical findings on new-onset fibromyalgia manifestations after non-hospitalized covid-19. MEDLINE, Web of Science, and APA PsycINFO were searched in a systematic scoping approach for empirical studies on new-onset fibromyalgia after non-severe non-hospitalized covid-19, charting study characteristics and outcome data. A total of 228 records were included. Various types of methods, tools, and study designs are being used for LC research, with inconsistency in key concepts and definitions. This leads to a fragmented understanding of the relationship between SARS-CoV-2 infection and LC. Prevalence studies of post-Covid fibromyalgia are ongoing and susceptible to bias. The empirical evidence supports an overlap between LC, chronic fatigue syndrome, and fibromyalgia but the molecular mechanisms still remain unclear. There are conflicting findings regarding presence of viral particles, central sensitization, autoantibodies, and more. This review highlights the need for standardized definitions and rigorous methodologies in research on LC. Future research should focus on epidemiological population-based studies with representative sampling and improving methodology, refining evolving definitions, harmonization of research, elucidating neurological mechanisms in hypothesis driven studies, and developing effective therapeutic strategies. The discussion synthesizes findings and offers an integrative mechanism for the pathophysiology of fibromyalgia and multisystem medically unexplained manifestations of LC as a non-autoimmune connective tissue disease. It helps explain neuropsychiatric and psychosomatic manifestations and is used to make testable theory-based predictions for future hypothesis-driven investigations.", "url": "https://pubmed.ncbi.nlm.nih.gov/42174645/" }, { "pmid": "42174604", "title": "Reframing ME/CFS: toward a unified mechanistic model of chronic post-infectious diseases.", "pub_date": "2026-05-23", "journal": "Journal of translational medicine", "authors": "Watton, Paul, Prusty, Bhupesh K", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multisystem illness marked by post-exertional malaise (PEM), cognitive dysfunction, autonomic disturbance, and impaired physiological resilience. Historically, the absence of validated biomarkers, heterogeneous definitions, and limited investigative capacity have complicated mechanistic interpretation and contributed to the use of psychosocial and rehabilitative frameworks in clinical practice and in parts of the literature. Advances in systems biology, accelerated by Long-COVID research, have transformed our understanding of post-infectious syndromes, implicating persistent immune dysregulation, mitochondrial and metabolic reprogramming, endothelial and microvascular dysfunction, abnormal coagulation, lipid-mediated signalling, extracellular vesicle communication, and viral protein-associated immune activation. This review charts the shift from early post-infectious observations through psychosocial dominance to contemporary biological frameworks, emphasising that pathology is state-dependent and revealed under physiological stress. ME/CFS is thus reframed here as a disorder of impaired adaptive capacity within post-infectious disease biology.", "url": "https://pubmed.ncbi.nlm.nih.gov/42174604/" }, { "pmid": "42167072", "title": "Longitudinal association of mental-health problems with subsequent diagnosis of persistent somatic symptom disorders: A large-scale registry-based observational study in primary care.", "pub_date": "2026-05-22", "journal": "General hospital psychiatry", "authors": "Kitselaar, Willeke M, Hartmann, Lea, Evers, Andrea W M, Numans, Mattijs E", "abstract": "Somatic symptoms of common persistent somatic symptom (PSS) syndromes like irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), and fibromyalgia (FM) are not fully attributed to well-established biomedical pathological processes. These syndromes are often under-recognized and diagnosis is often delayed. This study assessed the extent to which mental health problems precede the onset of IBS, CFS, and FM diagnoses using large-scale registry-based data from primary care settings. Data from 11,409 patients were anonymously extracted from primary care data-bases in the Netherlands. Cases (IBS, CFS, or FM) and non-cases were matched for age and sex using a 1:2 ratio. Associations with preceding mental health were available mental health-related registrations in the dataset (i.e., mental health-related ICPC-codes, referrals, and psychopharmaceuticals) registered prior to diagnosis. For predictive modeling, logistic LASSO regressions were applied. A total of 27 variables were longitudinally associated with IBS, CFS or FM (IBS k = 25, CFS k = 10, and FM k = 20). Five variables were longitudinally associated with all three syndromes (i.e., anxiety, psychosis, addiction behavior, and concentration disorders had positive predictive value and mental health-related referrals had negative predictive value). The overall classification performance of the models was fair (AUC Findings indicate that mental health-related registrations in primary care are associated with, vary between, and can accurately predict IBS, CFS, and/or FM. Prediction rules derived from mental health-related registrations might be able to support GPs in identifying patients with PSS. Future studies should investigate whether distinct decision rules are needed for the different syndromes.", "url": "https://pubmed.ncbi.nlm.nih.gov/42167072/" }, { "pmid": "42158223", "title": "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Successful Therapeutic Plasma Exchange Treatment After SARS-CoV-2 Infection-A Case Report.", "pub_date": "2026-05-20", "journal": "Clinical case reports", "authors": "Ciobanu, Georgiana, Arn, Norbert", "abstract": "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex neuroimmunological disorder characterized by disabling symptoms that are often difficult to manage. More recently, in the context of SARS-CoV-2 infection, potential pathophysiological overlaps and disease modulation have been hypothesized. Our successful case highlights the need to investigate novel therapeutic approaches, including plasma exchange.", "url": "https://pubmed.ncbi.nlm.nih.gov/42158223/" }, { "pmid": "42148664", "title": "Designing studies for post-treatment Lyme disease and other infection-associated chronic illnesses.", "pub_date": "2026-05-18", "journal": "Brain : a journal of neurology", "authors": "Arnaboldi, Paul M, Becker, Jacqueline, Nath, Avindra, Coyle, Patricia K et al.", "abstract": "Infection-associated chronic illnesses (IACIs) encompass a spectrum of poorly understood syndromes often marked by significant neurologic and multisystem symptoms following an infectious event. This review focuses on several diseases representative of the IACI spectrum. These are post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). Their clinical and biological complexity, combined with a lack of clear diagnostic criteria and objective available laboratory biomarkers, makes them difficult to distinguish from conditions with overlapping features. This presents challenges for research studies, as well as diagnosis and clinical management. This diagnostic ambiguity, coupled with heterogeneous patient presentations, has led to challenges in research, including misclassification of study participants and inconsistent or irreproducible findings. Some PTLDS research exemplifies these issues, which also extend to other IACIs. To advance the field, we highlight key methodological refinements and approaches for studying IACIs, including rigorous participant selection, standardized sample collection protocols, and the use of appropriate control groups, including those with microbiologic proof of the initial infection when known and technologically feasible. We also address broader influences on research quality, such as stigma, historical neglect, and the urgency to find treatments, which have contributed to the proliferation of poorly controlled studies and questionable practices. Drawing lessons from past challenges, we propose a path forward grounded in fit-for-purpose methodological rigour to improve scientific understanding and support evidence-based therapeutic development for IACIs.", "url": "https://pubmed.ncbi.nlm.nih.gov/42148664/" }, { "pmid": "42148468", "title": "Phenotypes of Chronic Overlapping Pain Multimorbidity in Rheumatology: A Population-Based Claims Study.", "pub_date": "2026-05-18", "journal": "Arthritis care & research", "authors": "Lu, Di, Cunanan, Kristen, Cragun, James, Vuong, Lauren et al.", "abstract": "This study aims to characterize the burden and distinct patterns of chronic overlapping pain conditions (COPCs) multimorbidity in adults with autoimmune rheumatic diseases (ARDs). We analyzed 2008 to 2021 data from the Merative MarketScan Commercial Claims and Encounters Database, identifying 149,742 patients with ARDs (ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, Sjögren disease, systemic lupus erythematosus, and systemic sclerosis) using International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification codes. We assessed COPC (eg, fibromyalgia, chronic low back pain, migraine, irritable bowel syndrome, chronic fatigue syndrome, temporomandibular disorders, and pelvic pain conditions) prevalence, multimorbidity patterns, and pairwise co-occurrence frequencies, calculating observed/expected ratios and odds ratios (ORs). Of 149,742 patients with ARDs, 57.5% had one or more COPCs, with 22.7% experiencing multiple conditions. Chronic low back pain (41.4%) and fibromyalgia (21.1%) were most prevalent. Women and individuals aged 31 to 50 years had the highest COPC prevalence. Many COPC pairs co-occurred more frequently than expected by chance (eg, fibromyalgia and chronic low back pain: observed/expected ratio 1.35; migraine and chronic low back pain: observed/expected ratio 1.42). Strongly associated dyads included urologic chronic pelvic pain and vulvodynia (OR 10.46). A substantial burden and distinct multimorbidity patterns of COPCs exist among patients with ARDs, suggesting shared pathophysiologic mechanisms. Routine COPC screening and targeted nonopioid multimodal interventions, especially for common dyads, are crucial for improved pain management and reducing opioid-related risks in this population.", "url": "https://pubmed.ncbi.nlm.nih.gov/42148468/" }, { "pmid": "42147023", "title": "Response: Commentary: Cognitive behavioural therapy for the treatment of chronic fatigue syndrome in adults: a short analysis of the meta-analysis.", "pub_date": "2026-05-18", "journal": "Frontiers in psychiatry", "authors": "Kolala, Vivek, La Rosa, Billie, Vangaveti, Venkat, Chen, Kai Yang", "abstract": "No abstract available.", "url": "https://pubmed.ncbi.nlm.nih.gov/42147023/" }, { "pmid": "42141452", "title": "Chronic fatigue syndrome in nursing practice: a concept analysis.", "pub_date": "2026-05-16", "journal": "BMC nursing", "authors": "Gao, Yazhuo, Zhu, Qianyin, Xu, Min", "abstract": "Nurses are essential in chronic fatigue syndrome (CFS) management, serving as care coordinators and patient advocates, but currently lack a unified guiding framework. CFS affects about 0.89% of the global population based on CDC-1994 criteria, with higher prevalence in women. Since its initial definition in 1988, over 25 diagnostic criteria have been introduced, leading to ongoing confusion about core symptoms and diagnosis. This inconsistency poses significant challenges for nurses, including difficulties in patient identification, inconsistent assessment approaches, and lack of standardized care pathways. A clear theoretical model is needed to improve nursing assessments, intervention planning, and care standardization. A concept analysis was conducted using the Walker and Avant's eight-step method. Eight databases were systematically searched for literature from January 1988 to December 2025. Studies on CFS definitions, diagnostic criteria, or conceptual frameworks were included if they addressed key attributes, antecedents, consequences, or measurement methods. Two graduate students and professors independently performed two-stage screening and data extraction. Multiple discussion rounds ensured analytical rigor. Sixty-eight studies were included. CFS antecedents included infections, immune dysregulation, genetics, and stress. Five core attributes were identified as defining features of CFS in the reviewed literature: persistent severe fatigue, post-exertional malaise (PEM), non-restorative sleep, cognitive impairment and/or orthostatic intolerance, and multisystem involvement. Consequences involved disability, poor quality of life, psychological distress, social isolation, and economic burden. Empirical referents included diagnostic criteria, symptom scales, and functional measures. This study proposed a nursing-oriented conceptual framework for CFS based on the reviewed literature, identifying five core features that may help distinguish it from general fatigue. The framework suggests plausible directions for nursing practice, including prioritizing PEM assessments, promoting energy management and pacing as potential interventions, and considering nurses as care coordinators in multidisciplinary teams. It may also contribute to CFS-focused nursing education and the development of assessment instruments. Given shared pathophysiological features reported in the literature, the framework may offer a conceptual basis for application to post-infectious fatigue conditions such as long COVID, though this transferability requires empirical validation in specific populations and clinical contexts.", "url": "https://pubmed.ncbi.nlm.nih.gov/42141452/" }, { "pmid": "42137851", "title": "A Perspective on Observation as Intervention in Chronic Diagnostic Complexity.", "pub_date": "2026-05-15", "journal": "Journal of patient experience", "authors": "Niederman, Caroline N", "abstract": "This patient perspective article advances observation as an intentional, rigorous form of clinical care rather than a passive absence of intervention. The recommendations arise from the lived experience of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), informed by clinical training as a mobile equine veterinarian. Over a nine-year diagnostic course, early clinical curiosity gave way to prolonged skepticism in the context of normal examinations and laboratory findings, ultimately shifting responsibility for daily functioning and symptom interpretation onto the patient. Across repeated encounters, subtle but consistent indicators of impaired energy regulation and exertional intolerance were present yet remained clinically unintegrated. When viewed longitudinally, these findings revealed a coherent physiological pattern that was not apparent at any single time point. Modern medical training emphasizes action. However complex, relapsing, and poorly understood conditions often demand sustained clinical attention before diagnostic clarity emerges. In the absence of immediate abnormalities, discomfort with uncertainty may prompt premature intervention or disengagement, eroding trust and obscuring evolving signals. Structured observation offers an alternative. As a clinical strategy, it preserves diagnostic curiosity, strengthens the physician-patient relationship, and allows for the observation of physiology without confounding influences. Such observation can yield meaningful insight and guide precise, compassionate care.", "url": "https://pubmed.ncbi.nlm.nih.gov/42137851/" }, { "pmid": "42136313", "title": "Recent Perspectives on the Physiological and Therapeutic Benefits of Placental Extracts in Chronic Noninfectious Diseases and Aging.", "pub_date": "2026-05-15", "journal": "Current medicinal chemistry", "authors": "Xinliang, Zhang, Dudnik, Elena N, Gavrikov, Leonid K, Liye, An et al.", "abstract": "Non-communicable diseases (NCDs), including metabolic disorders, cardiovascular diseases, liver pathologies, and age-related syndromes, are a major global health challenge. Human placental extract (HPE) and related formulations, such as Laennec and porcine-derived extracts, have been investigated as cell-free therapeutic agents capable of modulating physiological and immunological pathways. A systematic literature review was conducted using PubMed, MEDLINE, Scopus, Google Scholar, and the National Library of Medicine databases. Only original English-language research articles were included. Data were extracted on the biochemical composition, mechanisms of action, and therapeutic outcomes of placental extracts in preclinical and clinical studies. HPE was shown to enhance liver function by reducing oxidative stress, promoting hepatocyte regeneration, and regulating apoptosis and autophagy. In metabolic disorders and cachexia, it preserved muscle and adipose tissue and alleviated symptoms of cirrhosis and metabolic dysfunction- associated steatohepatitis. Laennec and porcine extracts improved iron metabolism, reduced hepatic fibrosis, and enhanced glucose regulation in type 2 diabetes and non-alcoholic fatty liver disease. Additional reported effects included anti-aging properties, relief in chronic fatigue syndrome, and dermatological benefits, such as reduced hair loss and improved allergic contact dermatitis. Placental extracts, such as HPE, Laennec, and porcine formulations, show promise for treating NCDs, including metabolic disorders, liver pathologies, and age-related syndromes. Preclinical and clinical studies highlight their mechanisms, which involve reducing oxidative stress, promoting hepatocyte regeneration, regulating apoptosis/autophagy, and improving iron metabolism and glucose control. Benefits include alleviating cirrhosis, type 2 diabetes, cachexia, chronic fatigue, and dermatological issues like hair loss. While the evidence is encouraging, largescale trials are needed to confirm their efficacy and the underlying molecular pathways. Placental extracts exhibited diverse therapeutic effects across multiple NCDs, mediated by immunomodulatory, antioxidative, and metabolic regulatory mechanisms. While current evidence from preclinical and clinical studies is promising, large-scale, rigorously designed trials are needed to validate efficacy and clarify molecular pathways.", "url": "https://pubmed.ncbi.nlm.nih.gov/42136313/" }, { "pmid": "42131622", "title": "Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.", "pub_date": "2026-05-14", "journal": "Open forum infectious diseases", "authors": "Ikeda, Gentaro, Koike-Ieki, Mariko, Inoue, Hiroyuki, Dadhania, Arya V et al.", "abstract": "Long COVID (LC) is characterized by symptoms persisting at least 3 months after SARS-CoV-2 infection and affecting multiple organ systems. Diagnosis relies on subjective criteria without established biomarkers. Immune dysregulation and mitochondrial dysfunction are implicated in LC pathophysiology. Given clinical overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), we investigated whether plasma extracellular vesicles (EVs) capture shared molecular signatures. Plasma EVs from 125 individuals across pandemic-era and prepandemic cohorts were analyzed. The pandemic-era cohort included COVID-Recovered, LC with ME/CFS phenotype (LC-ME/CFS), and ME/CFS without infection (pan-ME/CFS). The prepandemic cohort included ME/CFS and matched controls. Extracellular vesicles were isolated using size-exclusion chromatography. Concentration and size were assessed by nanoparticle tracking analysis, and surface markers and mitochondrial membrane potential were evaluated by flow cytometry. Both pan-ME/CFS and LC-ME/CFS exhibited elevated EV concentrations compared with COVID-recovered controls after false discovery rate (FDR) correction ( ME/CFS and LC-ME/CFS demonstrate partially overlapping immune cell-associated EV alterations. Mitochondrial membrane potential alterations within selected immune-derived EV subsets, particularly B cell-associated EVs, suggest immune-metabolic involvement. Plasma EV profiling may inform future biomarker development.", "url": "https://pubmed.ncbi.nlm.nih.gov/42131622/" }, { "pmid": "42129788", "title": "Phosphoproteomic analysis reveals differential associations between liver-spleen disharmony and qi-blood deficiency syndromes in chronic fatigue syndrome.", "pub_date": "2026-05-14", "journal": "Journal of translational medicine", "authors": "Zhang, Jiabao, Tian, Ying, Sun, Guanghan, Kang, Ruixiang et al.", "abstract": "Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest and is often accompanied by multiple somatic symptoms. The etiology of CFS remains poorly understood, and conventional Western medicine offers limited effective targeted therapies. In contrast, Traditional Chinese Medicine (TCM), which utilizes pattern differentiation-particularly the Liver-Spleen Disharmony Pattern (LSDP) and the Qi-Blood Deficiency Pattern (QBDP)-has demonstrated clinical efficacy in managing CFS. However, the molecular mechanisms underpinning TCM pattern classification in CFS remain largely unexplored. A total of 30 participants were enrolled in this study, including 10 CFS patients with LSDP, 10 CFS patients with QBDP, and 10 age- and sex-matched healthy controls (HC). Serum phosphoproteomic profiling was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS), which incorporated data-dependent acquisition (DDA) for spectral library construction and data-independent acquisition (DIA) for label-free quantification. Differentially phosphorylated sites (DPSs) and proteins (DPPs) were identified with thresholds of absolute fold change (|FC|) ≥ 1.2 and a Benjamini-Hochberg (BH)-corrected false discovery rate (FDR) < 0.05. Principal component analysis (PCA) was employed to assess global differences in phosphorylation profiles across groups, and functional enrichment analyses were performed to elucidate the biological functions of differential molecules. PCA revealed distinct clustering of phosphoproteomic profiles among the three groups, with high consistency across biological replicates (PC1 explained 19.3% of the total variance, and PC2 explained 15.9%). A total of 849 non-redundant DPSs and 586 non-redundant DPPs were identified across the three pairwise comparisons. The HC vs. LSDP comparison yielded the highest number of differential molecules (406 DPSs and 351 DPPs), with a balanced distribution of upregulated and downregulated events. In contrast, the HC vs. QBDP comparison was dominated by phosphorylation upregulation (61.2% of DPSs), while the QBDP vs. LSDP comparison showed a higher proportion of downregulated DPSs (56.7%). Functional enrichment analysis indicated that upregulated DPPs in the HC vs. LSDP comparison were primarily involved in MAPK signaling and cytoskeletal remodeling, while downregulated DPPs were enriched in pathways associated with neurodegenerative diseases and nucleocytoplasmic transport. Notably, we identified a candidate differential phosphorylation site, DENND3 S472 (S472@DENND3_HUMAN), with moderate discriminatory power (raw p = 0.042, BH-corrected FDR < 0.05, AUC = 0.72). This exploratory study identified significant differences in serum phosphoproteomic profiles between CFS patients with LSDP and QBDP. The distinct phosphoproteomic signatures observed in LSDP and QBDP provide preliminary molecular evidence supporting TCM pattern differentiation in CFS. These findings enhance the understanding of CFS pathogenesis and lay the groundwork for precision-based TCM diagnosis and individualized therapeutic strategies for CFS.", "url": "https://pubmed.ncbi.nlm.nih.gov/42129788/" }, { "pmid": "42129014", "title": "Sleep in myalgic encephalomyelitis/chronic fatigue syndrome shows marked night-to-night fluctuation under free-living conditions-results from a matched case-control study.", "pub_date": "2026-05-14", "journal": "Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine", "authors": "Saurel, Maïtena, Fornasieri, Isabelle, Del Sordo, Giovanna C, Chatain, Cyril et al.", "abstract": "Unrefreshing and non-restorative sleep is a hallmark complaint in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, little is known about their habitual sleep and night-to-night fluctuations under real-life conditions. This study aimed to characterize sleep, and the intraindividual variability (IIV) of sleep in people living with ME/CFS compared with matched controls. In this case-control study, 38 ME/CFS and 38 controls wore a wrist accelerometer continuously for 7 days and completed concurrent sleep diaries, the Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). Within the ME/CFS group, participants were also stratified by symptom severity using the Bell Disability Scale. Sleep IIV was quantified using the coefficient of variation, the root mean square of successive differences, and the Bayesian variability model, respectively. Compared with controls, individuals with ME/CFS spent significantly more time in bed and exhibited poorer sleep efficiency (SE) (all p < 0.05). Despite a longer time in bed, total sleep time did not differ between groups. ME/CFS participants also displayed significantly greater IIV in SE. By contrast, sleep timing (bedtime) was more regular among ME/CFS. Exploratory analyses did not detect clear differences across ME/CFS severity subgroups for mean sleep variables or variability indices. Under real-life conditions, people with ME/CFS exhibit poor sleep quality and unstable SE. These findings highlight sleep IIV as a clinically relevant dimension of sleep health in ME/CFS. Unrefreshing sleep is a core symptom of ME/CFS, yet most evidence relies on single- or two-night laboratory assessments that may not reflect habitual sleep under real-life conditions. Moreover, night-to-night sleep variability, a potentially critical dimension of sleep health, has not been systematically examined in ME/CFS. Using week-long wrist accelerometry, this study shows that under free-living conditions sleep in ME/CFS is characterized not only by impaired sleep efficiency but also by pronounced night-to-night variability, despite relatively stable bedtime compared to controls. These findings highlight sleep efficiency variability as a clinically relevant feature of ME/CFS and underscore the need for multi-night assessment and targeted strategies addressing sleep variability.", "url": "https://pubmed.ncbi.nlm.nih.gov/42129014/" }, { "pmid": "42125999", "title": "Molecular Mimicry Between Epstein-Barr Virus and Human Herpesvirus-6 Proteins and Central Nervous System Proteins: Implications for T and B Cell Immunogenicity in an In Silico Study.", "pub_date": "2026-05-13", "journal": "Immunity, inflammation and disease", "authors": "Almulla, Abbas F, Normatov, Muslimbek G, Supasitthumrong, Thitiporn, Maes, Michael", "abstract": "The Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) are frequently linked to neuropsychiatric illnesses such as multiple sclerosis, depression, and chronic fatigue syndrome/myalgic encephalomyelitis. These viruses may induce autoimmune reactions by molecular mimicry, leading to damage to self-epitopes in the central nervous system (CNS). This study seeks to explore the common pentapeptides present in EBV and HHV-6 viral antigens alongside various CNS-related proteins via molecular mimicry. Additionally, it will assess the immunogenicity of these shared pentapeptides in T and B cells. Sequence alignment was conducted to assess molecular mimicry between 32 EBV and HHV-6 antigens and 10 CNS autoantigens. Protein sequences were obtained from UniProt, structural homology was analyzed using AlphaFold and PyMol, and shared pentapeptides were identified with Alignmentaj. Immunogenicity was assessed via the Immune Epitope Database (IEDB) for potential T- and B-cell activation. A total of 91 mimicry pentapeptides were identified between viral antigens (42 EBV and 49 human HHV-6), and 10 CNS proteins. Notably, synapsin (SYN)1 exhibited the highest mimicry, sharing 13 pentapeptides with (7 with EBV and 6 with HHV-6) viral antigens such as EBV nuclear antigen (EBNA)1, EBNA6, latent membrane protein (LMP)1, and early antigen diffused (EA-D). Myelin proteins, including myelin-associated glycoprotein with 12 shared pentapeptides, myelin basic protein with 9, and myelin-oligodendrocyte glycoprotein with 5, displayed immune cross-reactivity with EBV/HHV-6 antigens. EBNA1, EBNA2, EBNA6, LMP1, LMP2, EA-D, and BLLF1 structurally resemble CNS autoantigens and act as immunoreactive epitopes for human T and B cells. Except for EBNA2 and protein U94, all share immunogenic pentapeptide sequences with SYN1. Shared pentapeptides suggest a link between viral infections and CNS autoimmunity. Further research is needed to clarify molecular mechanisms and explore targeted therapies to mitigate virus-induced neuroinflammation.", "url": "https://pubmed.ncbi.nlm.nih.gov/42125999/" }, { "pmid": "42123618", "title": "Imbalance of Excitatory and Inhibitory Neurotransmitter Systems in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.", "pub_date": "2026-05-13", "journal": "International journal of molecular sciences", "authors": "Wirth, Klaus J, Scheibenbogen, Carmen", "abstract": "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID-19 syndrome share a symptom profile, including severe fatigue, cognitive dysfunction, exertional intolerance, sleep disturbances, hypervigilance, and the paradoxical state of being \"wired but tired.\" A well-established finding is sympathetic hyperactivity with reduced vagal tone, typically interpreted as autonomic nervous system dysfunction. Emerging evidence, however, suggests a broader disturbance across multiple neurotransmitter systems. This paper reviews current knowledge on neurotransmitter systems implicated in ME/CFS and Long COVID, focusing on potential mechanisms of dysregulation and their roles in disease pathology and symptom generation, as well as implications for treatment. In addition to abnormalities of the noradrenergic system, disturbances in serotonergic, GABAergic, and glutamatergic signaling have been reported. Contributing factors may include autoimmunity, neuroinflammation, gut dysbiosis, epigenetic influences, and stressors such as orthostatic intolerance, metabolic strain, and pain. A shift favoring excitatory over inhibitory neurotransmission can lead to excessive neural activation, autonomic dysfunction, sensory hypersensitivities, sleep disturbances, and cognitive impairment. Reduced GABAergic tone combined with increased glutamatergic and noradrenergic activity may elevate skeletal muscle tone, contributing to calcium overload, mitochondrial dysfunction, exertional intolerance, and post-exertional malaise. Various pharmacological treatments may partially rebalance these neurotransmitter systems, but limited efficacy highlights the need for systematic investigation and individualized strategies.", "url": "https://pubmed.ncbi.nlm.nih.gov/42123618/" }, { "pmid": "42119693", "title": "What is the Role of \"the Psyche\"? Long COVID and ME/CFS as Test Cases for Evidence-Based and Patient-Centered Psychiatry and Psychotherapy.", "pub_date": "2026-05-13", "journal": "Psychiatrische Praxis", "authors": "Schomerus, Georg, Nicolas, Mirja Lisa, Fritz, Fabian, Schneider, Diana et al.", "abstract": "The role of psychological factors in the development and course of Long Covid (LC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a subject of controversial debate. We argue that psychologizing LC and ME/CFS carries significant risks: it leads to potentially harmful therapies, invalidates the patients' experience of illness, hinders effective interventions such as pacing, diverts focus from necessary physical diagnostics and treatment, disadvantages patients in medical assessments, and places a considerable additional burden on the families of affected children or other relatives. We show that many of the arguments presented for a psychological contribution are nonspecific or insufficiently supported by empirical evidence. Our essay therefore advocates for extreme caution in attributing psychological factors to these conditions, in the interest of a specific, evidence-based, and patient-centered psychiatry and psychotherapy. Nach wie vor wird kontrovers über die Rolle psychischer Faktoren bei der Entstehung und Aufrechterhaltung von Long Covid (LC) und Myalgischer Enzephalomyelitis /Chronisches Fatigue-Syndrome (ME/CFS) debattiert. Wir argumentieren, dass eine Psychologisierung von LC und ME/CFS erhebliche Risiken birgt: Sie führt zu potentiell schädlichen Therapien, invalidiert das Krankheitserleben der Betroffenen, erschwert wirksame Maßnahmen wie Pacing, lenkt den Fokus weg von notwendiger körperlicher Diagnostik und Therapie, benachteiligt die Betroffenen in der Begutachtung und belastet die Familien von betroffenen Kindern oder andere Angehörigen in erheblichem Maße zusätzlich. Wir zeigen, dass viele der angeführten Argumente für eine psychische Mitverursachung unspezifisch oder empirisch unzureichend begründet sind. Unser Essay plädiert daher für größte Zurückhaltung bei der Zuschreibung psychischer Faktoren im Interesse einer spezifischen, evidenzbasierten und patient*innenorientierten Psychiatrie und Psychotherapie.", "url": "https://pubmed.ncbi.nlm.nih.gov/42119693/" }, { "pmid": "42105038", "title": "Feasibility, Adherence, Acceptance and Usability of a Multimodal Telemonitoring for Pediatric Post-COVID Syndrome: A Bicentric Pilot Study.", "pub_date": "2026-05-10", "journal": "Journal of medical systems", "authors": "Oftring, Zoe S, Schmidt, Jeremy, Greenfield, Julia, Hägele, Matthias et al.", "abstract": "Existing healthcare infrastructure struggles to meet the complex care required for pediatric Post-COVID Syndrome (pPCS). Telemonitoring offers potential to enhance care access, reduce patient burden, and ensure continuity. This study introduces and evaluates a novel, multimodal telemonitoring concept for pPCS with high translational potential for broader pediatric chronic and post-infectious conditions. Telemonitoring included a patient app, digital sensors (spirometer, smartwatch), Patient Reported Outcome Measures, chat/video consultations (VC), and a medical telemonitoring platform. Patients aged 12-17 years with diagnosed PCS were recruited from two pPCS outpatient university clinics in Bielefeld and Munich, Germany. Monitoring lasted three months. Evaluation focused on feasibility, adherence, acceptance, and usability, using monitoring data, the System Usability Scale (SUS), Technology Usage Inventory (TUI), and a custom survey completed by patients and parents. 30 patients (mean age: 15y ± 1.9; 57% female (17/30); mean Baseline Bell-Score: 36.4) and 30 parents participated. Adherence was high, with an average of 3.4 (smartwatch) to 4.6 (spirometry) measurements/week. Questionnaire response rate was 86% (411/480) and 97% (58/60) of VCs were conducted. SUS scores indicated very high usability (patients: 81.25/100; parents: 75.42/100). TUI results showed low skepticism, and high interest. Telemonitoring supported symptom management independent of in-person visits, despite sensor connectivity issues. This is the first study to demonstrate successful integration of telemonitoring in pPCS, with high adherence and positive feedback from all stakeholders supporting its potential. Despite occasional technical challenges and resource needs, this concept shows promise for broader hybrid telemonitoring care implementation in PCS and other post-infectious syndromes. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), trial registration number: DRKS00029354. Registered 07 February 2023 - Retrospectively registered https://drks.de/search/en/trial/DRKS00029354/entails.", "url": "https://pubmed.ncbi.nlm.nih.gov/42105038/" }, { "pmid": "42104344", "title": "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome diagnostic reporting in the 2021-2023 National Health Interview Survey.", "pub_date": "2026-05-09", "journal": "BMC public health", "authors": "Fleig, Katherine, Nahin, Richard, Stussman, Barbara, Wilkerson, Miciah et al.", "abstract": "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disabling illness characterized by activity limitations associated with fatigue, post-exertional malaise (PEM), unrefreshing sleep, memory and concentration problems, orthostatic intolerance and painful discomfort. While typically considered to be a chronic condition, some persons who have had ME/CFS report no longer having the disorder. Here, the prevalence and characteristics of adults in the United States who self-report having an ME/CFS diagnosis and those who self-report no longer having ME/CFS are presented. The current study utilized publicly available data from the 2021-2023 National Health Interview Survey, which interviewed 86,655 United States civilian non-institutionalized adults about their health. For this study, participants were categorized into three groups: Current ME/CFS (individuals currently diagnosed with ME/CFS), Past ME/CFS (individuals who were previously diagnosed but no longer report having the condition), and Never ME/CFS (individuals who have never been diagnosed with ME/CFS). These groups were characterized using descriptive statistics. In the United States adult population, 20.7% of the estimated 1.5% adults who ever received an ME/CFS diagnosis report they no longer have the condition (Past ME/CFS). Overall the Past ME/CFS group reported experiencing symptoms less frequently, less difficulty with daily living, approximately equal prevalence of comorbidities, and better general health status than the Current ME/CFS group but remained significantly impaired compared to the Never ME/CFS group. However, 40-50% of adults with Past ME/CFS report symptoms and function similar to adults with Current ME/CFS and only approximately 25% had substantially less symptoms and better function compared to those with Current ME/CFS. Comorbidities did not differ significantly between the Current and Past ME/CFS groups. Further study to better understand the reasons why those in the Past ME/CFS group report no longer having the disorder is important for understanding the natural history and disease burden of ME/CFS. Studying symptomatic remissions, and the underlying physiology of improvement, could lead to identification of new disease modifying therapeutic approaches.", "url": "https://pubmed.ncbi.nlm.nih.gov/42104344/" }, { "pmid": "42103832", "title": "Interpreting hand grip strength in hospital employees with post-COVID syndrome compared to non-infected controls: a case-control study.", "pub_date": "2026-05-09", "journal": "Scientific reports", "authors": "Tack, Matthias, Gruber, Rosalie, Betting, Leia, Herbrandt, Swetlana et al.", "abstract": "Post-COVID syndrome (PCS) is characterized by a variety of persistent symptoms following SARS-CoV-2 infection, including fatigue among others. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a related neurological disorder primarily characterized by severe fatigue and post-exertional malaise. This exploratory study aimed to assess hand grip strength (HGS) in individuals with PCS to evaluate muscular performance and fatigability and to explore potential HGS-derived parameters associated with PCS. HGS was measured in 19 hospital employees with PCS (mean age 47.8; 89.5% female; 7 fulfilling ME/CFS criteria) and compared with 23 healthy controls (mean age 43.7; 69.6% female). Measurements were performed in two sessions separated by 60 min, each consisting of ten consecutive HGS measurements. Linear mixed model analysis indicated that HGS tended to be lower in PCS at specific measurement points, although no consistent overall group effect was observed. HGS was reduced in the second session in PCS but not in controls, suggesting possible alterations in recovery following repeated exertion. Exploratory analysis of 30 HGS-derived parameters using logisitic regression models in female participants identified parameters based on maximum, minimum, and mean force values as showing the most promising discriminatory patterns: however, predictive performace was moderate and should be interpreted with caution. Overall, HGS may provide insights into funcitional impairment in PCS and could serve as a supportive adjunct in clinical assessment, although its diagnostic utility requires validation in larger cohorts.", "url": "https://pubmed.ncbi.nlm.nih.gov/42103832/" }, { "pmid": "42100733", "title": "Chronic stress and cognitive dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: HPA axis dysregulation and hippocampal plasticity.", "pub_date": "2026-05-08", "journal": "Frontiers in neuroscience", "authors": "Kang, Hailan, Shao, Tianrui, Shi, Yuqing, Wang, Shilei et al.", "abstract": "Cognitive dysfunction is a common and disabling clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), often described by patients as \"brain fog.\" These symptoms typically manifest as difficulties in attention, memory, and concentration. Chronic stress has been proposed as an important contributing factor in ME/CFS. The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the stress response, and prolonged adverse stress may contribute to HPA axis dysregulation, including altered cortisol rhythmicity and impaired negative feedback regulation. Such dysregulation may be associated with cognitive dysfunction in ME/CFS through mechanisms involving neuroinflammatory responses, oxidative stress, and disturbances in neurotransmitter homeostasis. Studies suggest that these alterations may affect hippocampal structure and function, thereby contributing to impaired learning and memory processes. As a key brain region involved in cognition and stress regulation, the hippocampus may be implicated in the neurobiological mechanisms underlying cognitive dysfunction in ME/CFS. This review integrates current evidence on the potential role of HPA axis dysregulation and related neurobiological alterations in chronic stress-associated cognitive dysfunction in ME/CFS, with the aim of providing a theoretical basis for identifying potential intervention targets and informing strategies centered on HPA axis regulation.", "url": "https://pubmed.ncbi.nlm.nih.gov/42100733/" }, { "pmid": "42099393", "title": "Anti-fatigue mechanism of", "pub_date": "2026-05-08", "journal": "Frontiers in cell and developmental biology", "authors": "Zhang, Minda, Li, Haishen, Dai, Junhao, Wang, Xiaotong et al.", "abstract": "To investigate the differential efficacy of", "url": "https://pubmed.ncbi.nlm.nih.gov/42099393/" }, { "pmid": "42086409", "title": "Erythroid-hormonal axis in long COVID.", "pub_date": "2026-05-06", "journal": "Trends in molecular medicine", "authors": "Elahi, Shokrollah", "abstract": "Long COVID may reflect a failure of coordinated physiological recovery rather than persistent infection. Emerging evidence identifies inflammation-driven disruption of erythropoiesis and hormonal balance as central mechanisms linking immune dysregulation, metabolic stress, and persistent symptoms. This framework positions erythroid-endocrine pathways as key determinants of recovery and promising therapeutic targets.", "url": "https://pubmed.ncbi.nlm.nih.gov/42086409/" }, { "pmid": "42082813", "title": "Risk factors for severe post-COVID condition in children, adolescents, and young adults.", "pub_date": "2026-05-05", "journal": "European journal of pediatrics", "authors": "Donath, Quirin, Haegele, Matthias, Schindler, Daniela, Welzhofer, Tiziana et al.", "abstract": "Post-COVID condition (PCC) in children and young people (CYP, PCCcyp) remains a significant health burden. Early identification of patients at risk for severe disease, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is crucial for timely and adequate care. This monocentric, observational registry study, performed at a tertiary pediatric hospital in Germany, included CYP aged 7-25 years with PCCcyp at diagnosis. Standardized clinical assessment tools and patient-reported outcome measures were applied, including the novel Munich Long COVID Symptom Questionnaire (MLCSQ). Severe PCC was defined by chronic symptom clusters, Fatigue Severity Scale (FSS), Total Composite Autonomic Symptom Score-31 (COMPASS-31), SF-36 composite scores, Bell Score, and confirmed ME/CFS diagnosis. Among 120 participants, severe PCCcyp was associated with a higher number of acute symptoms (OR", "url": "https://pubmed.ncbi.nlm.nih.gov/42082813/" } ] }