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BiomarkersDiagnosticsCognitive Impairment

3D Virtual Reality Performance Metrics as a Future Fatigue Biomarker in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Ladek, Anja-Maria, Priebe, Leonie, Harrer, Thomas et al.·Biomedicines·2026

Researchers tested how quickly 60 ME/CFS patients and 60 healthy controls could react to visual tasks presented in 3D virtual reality. ME/CFS patients showed slower reaction times across all difficulty levels, and they improved less with practice than controls did. The study reports an association between ME/CFS and prolonged reaction times, though the findings are preliminary and whether this could become a reliable test for fatigue severity requires further validation.

E2 ModerateBehavioralPEM not requiredCross-Sectional

Who receives a diagnostic label for fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome? A study in the lifelines cohort.

Tattan, Mais, Hanssen, Denise J C, Rosmalen, Judith G M·Journal of psychosomatic research·2026

This study looked at over 150,000 people to understand why some people with ME/CFS, fibromyalgia, or irritable bowel syndrome receive a diagnosis while others with the same symptoms do not. The researchers found that only a small number of people who meet the criteria for these conditions actually get diagnosed—about 14% for ME/CFS. Several factors like sex, education level, other health conditions, and how often people visit doctors affected whether they received a diagnosis.

E2 ModerateCohortPEM unclearObservational

Sleep in myalgic encephalomyelitis/chronic fatigue syndrome shows marked night-to-night fluctuation under free-living conditions-results from a matched case-control study.

Saurel, Maïtena, Fornasieri, Isabelle, Del Sordo, Giovanna C et al.·Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine·2026

This study observed that people with ME/CFS who wore sleep-tracking wristbands for a week showed poorer sleep quality and more night-to-night variability in how well they slept compared to matched controls—even though they spent more time in bed. The sleep pattern was unstable from night to night, which may be an important feature of ME/CFS sleep problems that laboratory studies (typically 1–2 nights) do not capture.

SleepDiagnostics

Prediction of post-COVID chronic fatigue syndrome using data mining and machine learning techniques in Isfahan COVID cohort study.

Nematbakhsh, Shayan, Mohammadifard, Noushin, Riahi, Roya et al.·Journal of infection and public health·2026

Researchers used machine learning to identify factors associated with post-COVID fatigue in a cohort of 3,850 patients in Isfahan, Iran. The analysis identified 37 factors linked to fatigue; anxiety, BMI, depression, irritability, and memory issues were among the strongest predictors. A machine learning model achieved 85% accuracy at identifying patients at risk, though these results are based on observed associations and have not yet been validated in independent populations.

BiomarkersEnergy MetabolismDiagnostics

Metabolomic Classification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome via Explainable Ensemble Learning and Pareto-Guided Feature Selection.

Yagin, Fatma Hilal, Korkmaz, Yavuz, Colak, Cemil et al.·International journal of molecular sciences·2026

Researchers analysed blood metabolite patterns (small molecules in blood) from 106 people with ME/CFS and 91 healthy controls using machine learning to see whether these patterns could distinguish ME/CFS from health. A computer model called Explainable Boosting Machine achieved 91% accuracy in this one study group. Importantly, the findings remain preliminary—they describe associations observed in this cross-sectional sample and require external validation in new populations before clinical use.

E2 ModerateCohortPEM requiredCross-Sectional

Total blood volume and red blood cell volume are not associated with orthostatic intolerance in adults with myalgic encephalomyelitis/chronic fatigue syndrome.

Yamazaki, Tadahiro, Mancini, Donna M, Blate, Michelle et al.·Physiological reports·2026

Researchers measured blood volume in 49 adults with ME/CFS and tested how their bodies responded to standing (using a lean test). They found that about half had abnormal responses to position changes, but these abnormalities were not clearly linked to whether participants had low, normal, or high blood volume. The findings suggest that other body systems—like nerve function or blood vessel control—may be more important than blood volume alone in explaining why many ME/CFS patients feel dizzy or unwell when standing.

BiomarkersAutonomic Nervous SystemDiagnostics

E2 ModerateCohortPEM not requiredCross-Sectional

Symptom profiles and health-related quality of life in Korean adults with post-acute sequelae of SARS-CoV-2 infection (PASC): A latent profile analysis.

Kim, Su-Jin, Kim, Jinhee·PloS one·2026

This study examined symptom patterns in 629 Korean adults with long COVID (persistent symptoms ≥12 weeks after COVID-19). Researchers identified four distinct groups: people with few symptoms, moderate multi-body symptoms, fatigue and post-exertional malaise-dominant symptoms, and severe multi-body symptoms. Quality of life decreased substantially as symptom burden increased. The findings are observational and reflect one population; whether they apply to ME/CFS remains unclear.

DiagnosticsCognitive ImpairmentPost-Exertional Malaise

E2 ModerateDiagnosticPEM unclearCross-Sectional

Improving myalgic encephalomyelitis population sampling: Applying an online respondent-driven method to address biases in G93.3 register data.

Kielland, Anne, Liu, Jing, Tyldum, Guri et al.·Journal of health psychology·2026

This study looked at how well official medical records capture ME/CFS cases and who gets diagnosed. Researchers found that medical register data misses many cases and disproportionately underrepresents people from lower-income backgrounds. They used a new online method to find ME/CFS patients more accurately and checked whether official diagnoses matched recognized diagnostic criteria.

Phosphoproteomic analysis reveals differential associations between liver-spleen disharmony and qi-blood deficiency syndromes in chronic fatigue syndrome.

Zhang, Jiabao, Tian, Ying, Sun, Guanghan et al.·Journal of translational medicine·2026

Researchers compared blood protein markers in 30 people—10 with ME/CFS showing Traditional Chinese Medicine (TCM) 'Liver-Spleen Disharmony' patterns, 10 with 'Qi-Blood Deficiency' patterns, and 10 healthy controls—using advanced protein analysis. They observed different patterns of phosphorylated proteins (chemical modifications on proteins) between the two ME/CFS groups and healthy controls, suggesting that TCM pattern categories may have distinct molecular signatures. However, this is an early exploratory study with a small sample size, and these findings have not yet been replicated.

BiomarkersDiagnostics

DiagnosticsPost-Exertional Malaise

Interpreting hand grip strength in hospital employees with post-COVID syndrome compared to non-infected controls: a case-control study.

Tack, Matthias, Gruber, Rosalie, Betting, Leia et al.·Scientific reports·2026

This small study compared hand grip strength in 19 hospital workers with post-COVID syndrome (including 7 who met ME/CFS criteria) to 23 healthy controls. Researchers found that grip strength tended to be lower in the post-COVID group, particularly when tested a second time after a 60-minute break, which might suggest difficulty recovering after repeated effort. However, these are preliminary findings from a small group, and the authors note that grip strength alone is not reliable enough to diagnose post-COVID syndrome.

E2 ModeratePEM unclearRegistry-Resource

Risk factors for severe post-COVID condition in children, adolescents, and young adults.

Donath, Quirin, Haegele, Matthias, Schindler, Daniela et al.·European journal of pediatrics·2026

This observational study from a German pediatric hospital followed 120 children and young adults with post-COVID condition (PCC), observing that those with more severe illness were more likely to have had 12 or more symptoms during their initial COVID-19 infection, alongside other acute symptoms such as trouble concentrating and fainting-like episodes. One quarter of participants met criteria for ME/CFS, and all of these were in the severely affected group; by analogy, if similar patterns apply to ME/CFS patients, early identification of high-symptom-burden acute illness might help predict who develops severe long-term illness. These findings are preliminary and come from a single hospital site.

Severe MEAutonomic Nervous SystemDiagnosticsCognitive Impairment

BiomarkersDiagnosticsLong COVID Overlap

Microvascular remodeling and endothelial dysfunction across the post-COVID-19 spectrum: a prospective observational case-control study.

Wallraven, Timon, Günthner, Roman, Lethen, Isabelle et al.·BMC medicine·2026

Researchers studied blood vessel changes in the tiny vessels of the eye (using a technique called retinal vessel analysis) in people with post-COVID-19 syndrome and a subgroup meeting ME/CFS criteria, compared to people who recovered from COVID-19 and those never infected. People with post-COVID-19 syndrome, particularly those meeting ME/CFS criteria, showed narrower arteries and altered vessel patterns associated with worse symptoms and higher inflammation markers. While these findings are reported as preliminary observations, the relevance of post-COVID-19 vessel changes to ME/CFS specifically remains unclear, and this study does not yet establish whether such changes cause symptoms or could guide treatment.

E2 ModerateCohortPEM unclearLongitudinal

Can Depression Polygenic Risk Score Predict Postinfective Fatigue Syndrome (PIFS) in the Dubbo Infection Outcomes Study (DIOS)?

Ruseva, Albena G, Valencia, Braulio M, Gordon, Scott D et al.·Twin research and human genetics : the official journal of the International Society for Twin Studies·2026

Researchers studied whether genetic risk for depression or chronic fatigue could predict who would develop a fatigue syndrome after infection. In a group of 464 people followed after confirmed infection, they observed that neither depression genetics nor chronic fatigue genetics were associated with developing this condition overall—though a preliminary finding suggested depression genetics might affect risk differently in women versus men. These early results suggest genetic liability to depression or chronic fatigue alone may not be the main driver of postinfective fatigue syndrome.

BiomarkersDiagnostics

E2 ModerateCohortPEM not requiredCross-Sectional

The Diagnostic Journey of Dysautonomia Patients: Insights from a Patient-Reported Outcome Study.

O'Dell, John A, Walker, Ash, Latham, Andrew J et al.·Journal of patient experience·2025

This study followed 672 adults with dysautonomia (a condition where the nervous system that controls automatic body functions doesn't work properly) to understand how long it takes to get diagnosed and which doctors help with diagnosis. On average, it took 7.7 years for people to receive a diagnosis, and they often saw multiple types of doctors before getting answers. The study found that dysautonomia commonly occurs alongside other conditions like Ehlers-Danlos syndrome, mast cell disorders, and ME/CFS, which can make diagnosis even more confusing.

Autonomic Nervous SystemDiagnostics

E2 ModerateCohortPEM unclearRegistry-Resource

Unequal access to diagnosis of myalgic encephalomyelitis in England.

Samms, Gemma Louise, Ponting, Chris P·BMC public health·2025

This study examined NHS records from England to understand how many people have ME/CFS and whether diagnosis is fair across different groups. Researchers found that about 100,000 people in England have been officially diagnosed with ME/CFS, but the actual number may be much higher—around 404,000 in the UK. The diagnosis rates varied significantly depending on gender, age, ethnicity, and where people live, suggesting some patients are being missed.

DiagnosticsPost-Exertional Malaise

Quantifying the Degree of Fatigue in People Reporting Symptoms of Post-COVID-19 Syndrome: Results from a Rasch Analysis.

Mayo, Nancy, Brouillette, Marie-Josée, Fellows, Lesley K et al.·Physiotherapy Canada. Physiotherapie Canada·2025

Researchers in this study developed and tested a new questionnaire to measure fatigue severity in people with post-COVID-19 syndrome. The measure, called the PCS Fatigue Severity Measure V1, performed well in their analysis of 414 participants—it correlated strongly with other fatigue measures and distinguished between people still working and those on sick leave. However, this is early-stage research in a single Canadian cohort, and the authors note that further testing in other populations is needed to confirm the measure's reliability over time.

E2 ModerateCohortPEM unclearObservational

Assessing the influence of lived-experience experts on healthcare providers in a virtual community of practice: a qualitative study.

Weaver, Stephanie Sargent, Carry, Monique, Bertolli, Jeanne et al.·Frontiers in health services·2025

This study looked at whether having patients with lived experience of Long COVID and ME/CFS help teach doctors made a real difference in patient care. Researchers tracked what these patient-experts recommended to doctors through online training sessions from 2022-2024, and then asked actual patients if their doctors seemed to apply that advice. The main recommendations focused on validating patients' experiences, showing empathy, helping with referrals, and supporting self-care. Patients reported noticing positive changes in how their doctors treated them, suggesting that including patient-experts in medical education actually works.

E2 ModerateCohortPEM unclearObservational

Chronicity rhetoric in health and welfare systems inhibits patient recovery: a qualitative, ethnographic study of fibromyalgia care.

Cupit, Caroline, Finlay, Teresa, Pope, Catherine et al.·Social science & medicine (1982)·2025

This study looked at how healthcare and welfare systems talk about fibromyalgia and similar long-term conditions like ME/CFS. Researchers found that when doctors and officials constantly describe these conditions as permanent and unchangeable ('chronicity rhetoric'), it can actually get in the way of patients healing and recovering. The study suggests that changing how we talk about these conditions—and how our support systems are designed—might help patients feel more hopeful and do better.

E2 ModeratePEM unclearBiobank-Resource

Defining a High-Quality Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cohort in UK Biobank.

Samms, Gemma L, Ponting, Chris P·NIHR open research·2025

This study looked at how ME/CFS is identified in UK Biobank, a large database of health information from hundreds of thousands of people. Researchers found that about 1 in 100 UK Biobank participants had some evidence of ME/CFS, but only about one-third had strong, consistent evidence across multiple records. When they accounted for people too ill to participate in the study, they estimated that around 410,000 people in the UK have ME/CFS.

[Systems thinking, subjective findings and diagnostic "pigeonholing" in ME/CFS: A mainly qualitative public health study from a patient perspective].

Habermann-Horstmeier, Lotte, Horstmeier, Lukas Maximilian·Deutsche medizinische Wochenschrift (1946)·2024

This German study asked 544 ME/CFS patients about their experiences getting diagnosed and working with doctors. Patients reported that many doctors don't recognize ME/CFS as a real disease, instead dismissing it as purely psychological. The study found that poor diagnosis experiences and lack of doctor recognition of ME/CFS as a biological multisystem illness significantly damage the relationship between patients and their healthcare providers.