This month’s Research Digest highlights new research and developments across ME/CFS and long COVID. Studies explore widespread changes in circulating proteins in ME/CFS, links between gastrointestinal symptoms, inflammation and core disease features, and how post-exertional malaise (PEM) affects quality of life in long COVID. We also share two important Australian developments: the expansion of the AusME Biobank into Western Australia and the return of ME/CFS as a stand-alone condition in the Australian Burden of Disease Study.
Contributing Digesters: Lauren, Imogen, Anna & Simone.
Please note: The Research Digest shares current scientific findings for awareness and discussion. It is not a substitute for medical advice or treatment guidance, as much of the research featured is in its early stages and requires further confirmation.
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BIOLOGY
Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights
Authors: Hoel A, Hoel F, Dyrstad SE, Chapola H, Rekeland IG, Risa K, … Tronstad KJ (University of Bergen, Norway)
Publication: Cell Reports Medicine (March 2026)
Link: https://doi.org/10.1016/j.xcrm.2026.102647
Easy Read Overview: ME/CFS may involve problems with the immune system, blood vessels, and the way the body uses energy. Researchers found major differences in 1,823 proteins in people with ME/CFS compared with healthy people. Many proteins linked to muscles and energy were lower, while proteins linked to inflammation, blood clotting, and blood vessel function were higher. These findings suggest ME/CFS causes changes across several body systems and may help researchers develop better tests and treatments.
These authors hypothesise that ME/CFS involves an autoimmune mechanism that results in vascular dysfunction, causing tissue hypoperfusion and metabolic dysfunction. The authors aimed to identify biological pathways disrupted in ME/CFS by comprehensively profiling proteins circulating in the blood and examining how these changes relate to immune, vascular, and metabolic function. They also measured symptoms and physical activity (step count) to assess their association with circulating proteins.
This cross-sectional study analysed serum samples from 50 people with ME/CFS (Canadian Consensus Criteria) and 29 age- and sex-matched healthy controls. Researchers measured 7,326 protein targets using aptamer-based proteomics and validated selected findings using antibody-based assays in larger cohorts.
Compared with healthy controls, 1,823 protein targets differed significantly in ME/CFS. Intracellular proteins, particularly those associated with skeletal muscle and energy metabolism, were generally reduced, while secreted proteins involved in inflammation, complement activation, coagulation, and vascular regulation were increased. Immune analysis identified reduced proteins associated with neutrophils and monocytes despite normal blood cell counts, suggesting altered innate immune function. These changes were not explained by age, sex, BMI, fasting status, or reduced physical activity.
The authors suggest these proteomic patterns reflect widespread multisystem dysregulation involving immune, vascular, and metabolic pathways rather than deconditioning. They propose that the findings strengthen evidence for disrupted immune regulation and altered tissue homeostasis in ME/CFS, providing a framework for future biomarker development and therapeutic research.
BIOLOGY
Gastrointestinal symptoms correlate with core clinical features and systemic inflammation in myalgic encephalomyelitis/chronic fatigue syndrome
Author: Brown M, Vernon SD, Indart AC, Green PH, Alaedini A (Columbia University, USA)
Publication: Journal of Translational Medicine (June, 2026)
Link: 12967_2026_Article_8442.pdf
Easy Read Overview: People with ME/CFS had more stomach and bowel problems than healthy people, including IBS. More severe gut symptoms were linked to worse ME/CFS symptoms, especially flu-like feelings. People with worse gut symptoms also had higher levels of inflammation and stronger immune reactions to food and gut bacteria. The study suggests that gut and immune problems may play a role in some people with ME/CFS, but more research is needed to confirm this.
While considerable research has examined gastrointestinal (GI) symptoms and immune dysfunction in ME/CFS, these authors noted little research on whether these two aspects of the condition are related. This paper investigated whether gastrointestinal symptoms in ME/CFS were associated with specific clinical symptoms and immune changes.
The study included 116 people with ME/CFS (Fukuda and Canadian Consensus Criteria) and 80 healthy controls. Participants with ME/CFS had post-viral onset, PEM lasting >24 hours, significant cognitive impairment, and completed the RAND-36 quality of life questionnaire. Healthy controls were recruited from the same neighbourhoods, screened to exclude ME/CFS, and disqualified if they had major health conditions (e.g., cancer, psychiatric disorders, or liver disease). The groups were comparable in age, sex, race, and BMI.
Participants rated the frequency and severity of 54 ME/CFS symptoms across nine domains, including five GI symptoms: bloating, abdominal pain, nausea, loss of appetite, and bowel problems. These ratings were combined to generate symptom burden scores for each domain.
People with ME/CFS reported significantly more GI symptoms than healthy controls, with irritable bowel syndrome (IBS) also being more common. Greater GI symptom burden was moderately – strongly associated with worse symptoms across all nine domains, with the strongest association seen for flu-like symptoms.
People with more severe GI symptoms also had higher levels of inflammation (CRP). Those with more frequent flu-like symptoms showed stronger immune responses to food and gut bacteria, suggesting gut-related immune dysfunction may contribute to symptoms in a subset of ME/CFS patients.
The authors conclude that these results suggest that GI symptoms are closely linked to the severity of core ME/CFS symptoms and may possibly reflect an underlying gut-immune subtype. Although this study’s cohort was larger than previous ME/CFS studies, the results need to be confirmed in a larger, more diverse population.
QUALITY OF LIFE
Impact of post-exertional malaise frequency and fatigue in Long COVID patients on health-related quality of life
Author: Thölking T, Müller F, Riester T, Lampe V, Theil L-M, Hummers E, … Schröder D (University Medical Center, Germany)
Publication: Health and Quality of Life Outcomes (May, 2026)
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC13162394/pdf/12955_2026_Article_2523.pdf
Easy Read Overview: This study looked at how often and how severely post-exertional malaise (PEM) affects quality of life in people with long COVID. It found that people who had more severe or more frequent PEM had a lower quality of life, even after other factors were taken into account. Most participants reported problems with pain, everyday activities and mobility, and people who were not working had lower quality of life. The authors say these findings show the importance of recognising PEM as a key symptom and developing strategies that reduce both its severity and frequency.
This study sought to examine the impact of the frequency and severity of PEM on health-related quality of life (HRQoL) (including functionality and well-being) among people with long COVID.
Cross-sectional, online survey data were analysed from 161 adults (mean age 45.9 years, 85.1% female) with self-reported long COVID and PEM, residing in Germany. Long COVID was defined as symptoms for four or more weeks from a test-confirmed COVID infection. PEM was defined as exertion-induced symptom worsening after mild activity.
PEM frequency responses were categorised by researchers into daily, weekly, monthly or less frequent. PEM severity was measured using the 10-item Fatigue Assessment Scale (FAS). HRQoL was measured using the EQ-5D-3L scale (covering five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Data was analysed to investigate associations between PEM frequency, fatigue and HRQoL. Multiple linear regression was used to predict HRQoL while controlling for age, sex, employment status, number of comorbidities and perceived social status.
Regression models found greater PEM severity and more frequent PEM independently predicted lower HRQoL. Sex was not a significant predictor.
Participants most frequently reported problems in the domains of pain/discomfort (93.2% ), usual activities (91.9%), and mobility (59.0%). Participants not employed reported significantly lower HRQoL.
The overall HRQoL reduction (mean EQ-5D-3L = 55) among participants was substantial. The authors state these findings reflect other research finding individuals reporting long COVID have significantly lower HRQoL compared to people with other chronic diseases.
The authors suggest the findings underpin the importance of recognising PEM as a key symptom and highlight the need for patient-centred strategies to reduce the impact of PEM on quality-of-life. The authors also suggest future research and treatments address both PEM severity and frequency.
MEDIA
Emerge Australia & ECU Collaboration
Publication: 7News Perth
Link: https://emerge.org.au/news/7-news-perth-ausme-and-ecu-collaboration/
A collaboration between Emerge Australia and ECU has allowed the AusME Biobank to expand its collection sites for blood samples into WA. Seventeen new collection sites have opened across Western Australia, allowing people to donate blood for ME/CFS and long COVID research.
Stacey Hollings, bedbound with ME/CFS, talks about living with the condition and what it would mean to her to have better treatments.
MEDIA
ME/CFS returns to the Australian burden of disease study
Author: Tracy, L
Publication: Medical Republic
Link: https://www.medicalrepublic.com.au/me-cfs-returns-to-the-australian-burden-of-disease-study/128150
The Australian Institute of Health & Welfare’s Australian Burden of Disease Study (ABDS) will include ME/CFS as a stand-alone condition for the first time since 2003. This important study compares the impact of different health conditions and provides evidence to help guide government decisions about health services, funding and priorities.
Anne Wilson, CEO of Emerge Australia, said, “The inclusion of ME/CFS in the ABDS signifies official recognition of the substantial public health burden this condition imposes. It places ME/CFS alongside major health challenges such as cancer, cardiovascular disease, and mental health disorders, paving the way for informed policy development and resource allocation.”
