ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

41–60 of 298 studies

E2 ModerateCohortPEM unclearCross-Sectional

Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights.

Hoel, August, Hoel, Fredrik, Dyrstad, Sissel Elisabeth et al.·Cell reports. Medicine·2026

Researchers analyzed thousands of proteins in the blood of ME/CFS patients and compared them to healthy people. They found significant differences in protein patterns, including too much of certain immune-related proteins and too little of proteins normally made by muscles. These differences might help explain why ME/CFS causes such severe exhaustion and could eventually lead to new ways to diagnose or treat the condition.

BiomarkersImmune System

E2 ModerateCohortPEM unclearCross-Sectional

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.

Cambras, Trinitat, Domingo, Joan Carles, Sanmartín-Sentañes, Ramon et al.·Journal of translational medicine·2026

This study observed patterns of light exposure in 100 ME/CFS patients and 56 healthy controls over one week, using wrist-worn devices to track light, activity, and body temperature. Researchers found that ME/CFS patients with more stable daytime light exposure reported lower fatigue, better sleep, and higher quality of life compared to those with irregular or nighttime-dominant light patterns; these associations were not observed in healthy controls. The findings suggest light exposure patterns may be worth studying as a potentially modifiable lifestyle factor, though the study cannot prove that changing light exposure would improve symptoms.

BiomarkersInterventionsSleepAutonomic Nervous System

E2 ModerateCohortPEM unclearCase-Control

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.

BiomarkersDiagnosticsLong COVID Overlap

E2 ModerateCohortPEM unclearCross-Sectional

Elevated serum levels of interleukin-11 and matrix metalloproteinase-9 in myalgic encephalomyelitis/chronic fatigue syndrome.

Chinnappan, Baskaran, Kempuraj, Duraisamy, Aenlle, Kristina K et al.·Frontiers in immunology·2026

Researchers measured two immune proteins (IL-11 and MMP-9) in the blood of 40 ME/CFS patients and compared them to healthy controls, finding higher levels in the ME/CFS group. In the laboratory, they also showed that immune cells called mast cells release MMP-9 when exposed to a protein from Epstein-Barr virus. These are preliminary observations in one study that suggest these proteins may be associated with ME/CFS, but this does not yet establish their role in the disease.

NeuroinflammationBiomarkersImmune System

E2 ModerateCohortPEM unclearCase-Control

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

E2 ModerateCohortPEM unclearCross-Sectional

Raman Spectroscopy Combined with Machine Learning Reveals Myalgic Encephalomyelitis-Associated Biomolecular Signatures at Rest and After Standardized Stress.

Heidarifard, Maryam, Moezzi, Atefeh, Dallaire, Frédérick et al.·International journal of molecular sciences·2026

Researchers used a laboratory technique called Raman spectroscopy combined with computer learning to identify chemical signatures in blood plasma that are associated with ME/CFS. They collected blood samples from 115 ME/CFS patients and 45 healthy controls both at rest and 90 minutes after a standardized stress test, and found the method could distinguish between the two groups with moderate-to-good accuracy (79–84%). However, this is an early-stage study and much more work is needed before such a test could be used in clinical practice.

BiomarkersDiagnosticsPost-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

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.

BiomarkersEnergy MetabolismDiagnostics

E2 ModerateCohortPEM unclearCross-Sectional

Exploring differences in protein cargo of extracellular vesicles from ME/CFS patient plasma compared to healthy controls.

Rydland, Anne, Yran, Elena Støvring, Nyman, Tuula A et al.·Biochemistry and biophysics reports·2026

Researchers compared tiny particles called extracellular vesicles (EVs) in the blood of 49 ME/CFS patients and 50 healthy controls. They found that ME/CFS patients had higher concentrations of these particles, and 11 proteins inside them were observed at different levels in ME/CFS compared to controls—though these differences did not remain statistically significant after accounting for multiple comparisons. The study is exploratory and the authors note that further investigation is needed to understand whether these EV changes are relevant to ME/CFS.

BiomarkersImmune System

E2 ModerateCohortPEM unclearObservational

Exploratory clinical and immunological changes following Tixagevimab/Cilgavimab administration in immunodeficient patients with SARS-CoV-2-associated ME/CFS and persistent circulating spike protein.

Seidel, Maximilian, Anft, Moritz, Wiemers, Lea et al.·Immunology letters·2026

Researchers gave a monoclonal antibody treatment (Tixagevimab/Cilgavimab) to nine immunodeficient patients with long COVID and ME/CFS-like symptoms who had detectable coronavirus spike protein in their blood. After 30 days, one immune marker (β1-adrenergic receptor autoantibody) showed a modest decrease, but spike protein levels and symptom outcomes did not change significantly as a group. These are very preliminary findings from a small study without a control group, and the authors emphasise that efficacy remains uncertain.

BiomarkersInterventionsAutonomic Nervous SystemImmune System

E2 ModerateCohortPEM not requiredCross-Sectional

Subclinical Hypercoagulable Viscoelastic Characteristics Associated with Post-Acute Sequelae of SARS-CoV2 Physical Symptoms in COVID-19 ALI/ARDS Survivors.

Jones, Ansley E, Mira-Sanchez, Margarita, Khan, Zain et al.·Journal of intensive care medicine·2026

This study examined blood clotting patterns in 93 people who survived severe COVID-19 requiring hospitalization, testing them 15 months after discharge. Researchers observed that those with lingering post-COVID symptoms—particularly fatigue and post-exertional malaise (worsening after activity)—showed altered clotting characteristics on specialized blood tests, specifically higher fibrinogen levels. However, this is a single cross-sectional study and does not establish whether these clotting changes cause the symptoms or are simply associated with them.

BiomarkersLong COVID Overlap

E2 ModerateCohortPEM unclearObservational

Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study.

Gile, Brooke, Bulbule, Sarojini, Toriola, Mubaraq A et al.·Journal of translational medicine·2026

A pilot study observed that people with ME/CFS who received low-dose rapamycin reported improvements in fatigue symptoms over 90 days, and blood tests showed changes in purine metabolism and mitochondrial energy markers. However, this was a small observational study without a placebo control group, so it does not yet establish whether rapamycin actually causes these improvements or whether the observed biochemical changes are responsible for symptom relief.

NeuroinflammationBiomarkersEnergy MetabolismInterventions

E2 ModerateCohortPEM unclearCross-Sectional

Identifying EEG biomarkers of fatigue and brain fog in long COVID: insights from rest and movement-related brain activity.

Casado Sánchez, M, Morales Fajardo, K, Long, S et al.·Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia·2026

A small study measured brain electrical activity in 20 people with long COVID who reported fatigue and brain fog, compared to 20 healthy controls. Researchers observed two types of altered brain patterns in the long COVID group: weaker electrical responses after hand movements and slower brain waves at rest in motor and sensory regions. These patterns were associated with cognitive symptoms and fatigue, but it remains unclear whether these brain changes explain the symptoms or are simply observed alongside them.

BiomarkersCognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis.

Souma, Bernard, Elremaly, Wesam, Akoume, Marie-Yvonne et al.·International journal of molecular sciences·2026

Researchers compared blood levels of two proteins—irisin and thrombospondin-1 (TSP-1)—in 92 ME/CFS patients and 44 healthy controls, measuring them before and after a physical stress test. They observed that ME/CFS patients had lower baseline irisin levels and a weaker response to the stress challenge, while those with more severe symptoms showed elevated levels of both proteins. The study proposes that TSP-1 may interfere with irisin's normal signaling, potentially contributing to energy problems in ME/CFS, but these findings are preliminary and require validation in larger studies.

BiomarkersEnergy MetabolismPost-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Microstructural alterations in brain tissue of ME/CFS and long COVID using diffusion tensor imaging and diffusion kurtosis imaging.

Singh, Tanoj Bahadur, Marshall-Gradisnik, Sonya, Barnden, Leighton et al.·Frontiers in medicine·2026

Researchers used specialized brain imaging scans (DTI and DKI) to observe differences in brain tissue structure between people with ME/CFS, people with long COVID, and healthy controls. They found that ME/CFS and long COVID showed microstructural changes in different brain regions, though the study is cross-sectional and cannot explain why these changes occur or what role they play in symptoms. These are preliminary findings that require replication in larger groups.

BiomarkersCognitive ImpairmentLong COVID Overlap

E2 ModerateCohortPEM unclearCross-Sectional

Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.

Aregawi, Lillian, Walitt, Brian, Sullivan, Patti et al.·Brain communications·2026

Researchers measured levels of norepinephrine (a brain chemical) in cerebrospinal fluid from people with ME/CFS, Long COVID, and Parkinson's disease, comparing them to healthy volunteers. They observed that norepinephrine pathway activity was lower in all three patient groups, and in Long COVID patients with post-exertional malaise, this reduction was particularly pronounced. This is one study in a small sample, and it remains unclear whether these findings fully explain fatigue and brain fog or apply directly to ME/CFS.

BiomarkersCognitive ImpairmentLong COVID OverlapPost-Exertional Malaise

E2 ModerateCohortPEM unclearLongitudinal

Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

Jones, Ansley E, Khan, Zain, McGroder, Claire F et al.·Critical care explorations·2026

This study followed people who were hospitalized with severe COVID-19 for 3 years after they left the hospital. About one-quarter of them continued to experience long COVID symptoms like fatigue, brain fog, and difficulty with physical activity. Surprisingly, when researchers measured inflammation and blood vessel markers in their blood, these markers were not elevated and did not explain why some people had ongoing symptoms.

BiomarkersImmune SystemPost-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Inderyas, Maira et al.·Frontiers in neuroscience·2026

Researchers used a brain imaging technique called DTI-ALPS to measure how well the brain clears waste during sleep in 31 ME/CFS patients and 27 healthy controls. They observed that ME/CFS patients had lower measurements than controls, and these measurements were associated with worse sleep disturbance and concentration problems. However, this is a preliminary study in a small group, and it remains unclear whether reduced glymphatic function actually causes ME/CFS symptoms or is simply correlated with them.

NeuroinflammationBiomarkersSleepCognitive Impairment

E2 ModerateCohortPEM unclearCase-Control

Circulating extracellular vesicles-microRNAs as potential biomarkers for the identification of ME/CFS: differentiating fatigue-related conditions.

Eguchi, Akiko, Kuratsune, Hirohiko, Nakatomi, Yasuhito et al.·Journal of translational medicine·2026

Researchers analysed tiny particles called extracellular vesicles in blood samples from patients with ME/CFS, chronic fatigue without a known cause, and depression, looking for differences in small RNA molecules that could help diagnose ME/CFS. They found a pattern of 114 different RNA molecules that appeared associated with ME/CFS and were rarely seen in healthy people, though these findings come from a small group of patients and have not yet been replicated in larger studies.

NeuroinflammationBiomarkersDiagnosticsLong COVID Overlap

E2 ModerateCohortPEM unclearObservational

Wearable Heart Rate Variability Monitoring, Autonomic Dysfunction and Post-exertional Malaise in Long COVID: An Observational Study.

Ruijgt, Twan M, Slaghekke, Anouk, Ellens, Anneke et al.·Sports medicine (Auckland, N.Z.)·2026

This observational study measured heart rate variability (a marker of nerve system balance) in 121 long COVID patients and 21 healthy controls using wearable devices over multiple days. Researchers observed that long COVID patients had lower heart rate variability during daily activities and sleep, and their heart rate variability remained reduced for 24 hours after exercise, particularly at intensities above their aerobic threshold. The findings suggest wearables may help patients recognise when they are overexerting, though the study does not yet establish whether this monitoring prevents post-exertional malaise.

BiomarkersAutonomic Nervous SystemDiagnosticsPost-Exertional Malaise

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

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Evidence Atlas

Evidence browser

Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights.

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.

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

Elevated serum levels of interleukin-11 and matrix metalloproteinase-9 in myalgic encephalomyelitis/chronic fatigue syndrome.

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

Raman Spectroscopy Combined with Machine Learning Reveals Myalgic Encephalomyelitis-Associated Biomolecular Signatures at Rest and After Standardized Stress.

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

Exploring differences in protein cargo of extracellular vesicles from ME/CFS patient plasma compared to healthy controls.

Exploratory clinical and immunological changes following Tixagevimab/Cilgavimab administration in immunodeficient patients with SARS-CoV-2-associated ME/CFS and persistent circulating spike protein.

Subclinical Hypercoagulable Viscoelastic Characteristics Associated with Post-Acute Sequelae of SARS-CoV2 Physical Symptoms in COVID-19 ALI/ARDS Survivors.

Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study.

Identifying EEG biomarkers of fatigue and brain fog in long COVID: insights from rest and movement-related brain activity.

Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis.

Microstructural alterations in brain tissue of ME/CFS and long COVID using diffusion tensor imaging and diffusion kurtosis imaging.

Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.

Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS.

Circulating extracellular vesicles-microRNAs as potential biomarkers for the identification of ME/CFS: differentiating fatigue-related conditions.

Wearable Heart Rate Variability Monitoring, Autonomic Dysfunction and Post-exertional Malaise in Long COVID: An Observational Study.

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

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