Tag: 2026

Multi-omics analysis of long COVID (post-COVID-19 condition) reveals persistent mitochondrial dysfunction, suppressed oxidative phosphorylation, and immune dysregulation

Abstract:

Introduction: Post-COVID Syndrome (PCS), or long-COVID, is a major public health burden, but its underlying mechanisms remain poorly understood. Because acute SARS-CoV-2 infection induces marked suppression of mitochondrial oxidative phosphorylation (OXPHOS), we investigated whether persistent immunometabolic remodeling is a recurring transcriptional, metabolic, and proteomic feature of PCS.

Methods: We performed an integrated multi-omics analysis of transcriptomic, proteomic, and metabolomic datasets across multiple tissues from Syrian hamster models and human cohorts spanning acute infection through post-acute and PCS stages extending up to 12 months post-infection.

Results: Across species and tissues, we observed overlapping signatures of mitochondrial dysfunction, including sustained suppression of OXPHOS, activation of mitochondrial stress responses, and enrichment of inflammatory pathways. Skeletal muscle exhibited the most pronounced and persistent mitochondrial repression in both hamsters and PCS patient biopsies, consistent with fatigue-associated phenotypes. Hamster heart and kidney tissues also showed persistent OXPHOS suppression, while lung tissue demonstrated prolonged inflammatory signaling despite partial metabolic recovery. In the nervous system, transcriptional profiles revealed region-specific patterns, including persistent cortical mitochondrial repression and partial recovery in sensory-associated regions. Peripheral blood mononuclear cells (PBMCs) transcriptomics and serum metabolic datasets suggested prolonged downregulation of OXPHOS-associated programs up to 12 months post-infection, potentially contributing to persistent immune dysregulation in susceptible individuals with underlying conditions. Longitudinal serum proteomics in PCS patients revealed sustained mitochondrial stress responses, increased oxidative stress signatures, and persistent immune activation at 1 and 6 months post-infection compared to recovered controls.

Discussion: Together, these multi-omics results identify persistent mitochondrial repression and immune dysregulation as recurring features across PCS-associated datasets, providing a framework linking bioenergetic dysfunction with chronic immune activation and supporting future mechanistic and therapeutic investigation.

Source: Tasoula A, Arif S, Waisberg E, Bauer L, Aslinger E, Guarnieri JW. Multi-omics analysis of long COVID (post-COVID-19 condition) reveals persistent mitochondrial dysfunction, suppressed oxidative phosphorylation, and immune dysregulation. Front Immunol. 2026 May 21;17:1776555. doi: 10.3389/fimmu.2026.1776555. PMID: 42253978; PMCID: PMC13234542. https://pmc.ncbi.nlm.nih.gov/articles/PMC13234542/ (Full text)

Health-related quality of life changes in patients with Q-fever fatigue syndrome: a four-year follow-up study, 10 years post-infection

Abstract:

Purpose: Q-fever can cause long-term health complications such as Q-fever Fatigue Syndrome (QFS), which may severely impact patients’ Health-Related Quality of Life (HRQoL). This study investigated change of HRQoL in QFS patients over time, and explored predictors associated with change using longitudinal data.

Methods: In this prospective observational study questionnaires were administered among Dutch individuals with self-reported QFS who were registered at Q-support, a foundation that supports, advises and informs Q-fever patients. Participants completed four annual questionnaires between 2021 and 2024, including EQ-5D-5L and EQ VAS to measure HRQoL. Changes in HRQoL were categorized as “improvement”, “deterioration”, or “stable”, using an anchor-based minimal important difference approach. Multinomial logistic regression analyses identified predictors of change.

Results: A total of 199 patients were included in the final analysis. At baseline, median EQ-5D-5L utility index and EQ VAS scores were 0.647 (IQR: 0.352-0.774), and 50.0 (IQR: 34.0-60.0), respectively. After four years, 37% of patients showed improvement in EQ-5D-5L utility, 30% deterioration, and 33% remained stable. Female sex and higher baseline EQ-5D-5L utility were associated with lower odds of improvement or being stable.

Conclusion: More than 10 years post-infection, HRQoL remains consistently low at group level among patients with QFS, with substantial long-term variability in individual outcomes. These findings underscore the chronic nature of QFS, its long-lasting consequences, and the importance of continued monitoring of individual health trajectories. Further studies are warranted to better understand the mechanisms underlying individual differences in recovery and to inform targeted interventions for this patient population.

Source: Stemerdink NC, Heemskerk SCM, Hartman E, Wesseling M, Tieleman P, Burdorf A, Haagsma JA. Health-related quality of life changes in patients with Q-fever fatigue syndrome: a four-year follow-up study, 10 years post-infection. Qual Life Res. 2026 Jun 8;35(7):191. doi: 10.1007/s11136-026-04295-9. PMID: 42260029; PMCID: PMC13246837. https://pmc.ncbi.nlm.nih.gov/articles/PMC13246837/ (Full text)

A new patient-led approach to building research infrastructure and evidence generation

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.

Source: Cousins O, Leeming H, Putrino D, Gordon J. A new patient-led approach to building research infrastructure and evidence generation. Oxf Open Immunol. 2026 May 19;7(1):iqag009. doi: 10.1093/oxfimm/iqag009. PMID: 42261335; PMCID: PMC13242947. https://pmc.ncbi.nlm.nih.gov/articles/PMC13242947/ (Full text)

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study

Abstract:

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT06118138. Registered 01 November 2023 – Retrospectively registered, https://clinicaltrials.gov/study/NCT06118138?cond=ME%2FCFSamp;term=HBOTamp;rank=1.

Source: Kim L, Cammà G, Peters CK, Mantwill M, Müller O, Leprêtre N, Heindrich C, Rust R, Krill M, Hartung TJ, Reeß LG, Krohn S, Heymann CV, Wittke K, Finke C, Scheibenbogen C. Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study. J Transl Med. 2026 Jun 5. doi: 10.1186/s12967-026-08324-6. Epub ahead of print. PMID: 42249466. https://link.springer.com/article/10.1186/s12967-026-08324-6 (Full study available as PDF file)

Novel activity and participation scales for children, adolescents, and young adults with postacute infection and vaccination syndromes and/or ME/CFS

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.

Source: Weidmann C, Grabbe A, Eberhartinger M, Kircher A, Leone A, Warlitz C, Stojanov S, Behrends U, Mihatsch LL. Novel activity and participation scales for children, adolescents, and young adults with postacute infection and vaccination syndromes and/or ME/CFS. Eur J Pediatr. 2026 Jun 5;185(7):471. doi: 10.1007/s00431-026-07125-9. PMID: 42249231. https://link.springer.com/article/10.1007/s00431-026-07125-9 (Full text)

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

Abstract:

in English, German

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

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

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

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

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

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

Abstract:

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

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

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

Abstract:

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

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

Abstract:

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

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

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

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

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

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

Abstract:

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

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

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

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

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