ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

3941–3960 of 6,209 studies

E3 PreliminaryReviewPEM unclearReview-Narrative

Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.

Fronticelli Baldelli, Giovanni, Buonsenso, Danilo·Children (Basel, Switzerland)·2025

This review proposes that a protein called mTOR may be the key link between infections and the long-lasting symptoms seen in ME/CFS and similar post-infection illnesses. The authors suggest that when mTOR stays overactive after an infection, it can damage the barrier that protects the brain, allow immune cells to enter brain tissue, and cause ongoing inflammation that affects how the brain works. They outline a step-by-step pathway explaining how this might happen and suggest that targeting mTOR could be a new treatment approach.

NeuroinflammationImmune System

E3 PreliminaryMechanismPEM unclearMechanistic

Metabolic adaptation and fragility in healthy 3Din vitroskeletal muscle tissues exposed to chronic fatigue syndrome and Long COVID-19 sera.

Mughal, Sheeza, Andújar-Sánchez, Félix, Sabater-Arcis, Maria et al.·Biofabrication·2025

Researchers grew human muscle tissue in the laboratory and exposed it to blood from ME/CFS and Long COVID patients to see what happens. They found that muscle exposed to patient blood initially tries to work harder by burning more fuel, but over time the muscle becomes weak and fragile. The mitochondria (the energy-producing structures in cells) also change shape and stop working properly, suggesting the muscle is struggling under stress.

Energy Metabolism

E3 PreliminaryCommentaryPEM unclearEditorial

Reframing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Biological Basis of Disease and Recommendations for Supporting Patients.

Agarwal, Priya, Friedman, Kenneth J·Healthcare (Basel, Switzerland)·2025

This article is a special essay about ME/CFS that was written by a medical student and selected as the best submission in a scholarship competition. It explains what we currently know about how ME/CFS affects the body and offers practical advice for doctors on how to better care for ME/CFS patients. The essay highlights that ME/CFS is a serious, worldwide health problem affecting millions of people, many of whom haven't been properly diagnosed.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Language Matters: What Not to Say to Patients with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Other Complex Chronic Disorders.

Smyth, Nancy J, Blitshteyn, Svetlana·International journal of environmental research and public health·2025

This study examines how healthcare providers talk to patients with Long COVID and ME/CFS, and how certain words and phrases can hurt patients emotionally and damage the doctor-patient relationship. The authors identified problematic language patterns used by doctors and suggest better ways to communicate with compassion and respect. The goal is to help healthcare providers have more supportive conversations with patients who have these complex, poorly understood illnesses.

E3 PreliminaryCohortPEM unclearCase-Control

Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome in patients with bipolar affective disorder: A case report.

Nakajima, Kan, Ayani, Nobutaka, Matsuoka, Teruyuki et al.·PCN reports : psychiatry and clinical neurosciences·2025

This case report describes one patient with bipolar disorder who developed ME/CFS after COVID-19 and was treated with different types of steroid medications. Strong steroids (betamethasone and prednisolone) triggered a severe manic episode requiring hospitalization, but a weaker steroid (hydrocortisone) improved her fatigue without worsening her mood. The findings suggest that choosing the right type of steroid may be important for ME/CFS patients who also have mood disorders.

Endocrine Disruption

E3 PreliminaryReviewPEM requiredReview-Narrative

Advocating the role of trained immunity in the pathogenesis of ME/CFS: a mini review.

Humer, Bart, Dik, Willem A, Versnel, Marjan A·Frontiers in immunology·2025

This review explores how a single severe infection might trigger long-term changes in the immune system that could lead to ME/CFS. After infection, immune cells can become 'trained' to overreact to future triggers, potentially causing the chronic symptoms patients experience. The researchers suggest this overactive immune response might explain why about 60% of ME/CFS patients remember getting sick before their symptoms started.

Immune SystemPost-Exertional Malaise

E3 PreliminaryCohortPEM requiredObservational

Two-day cardiopulmonary exercise testing in long COVID post-exertional malaise diagnosis.

Gattoni, Chiara, Abbasi, Asghar, Ferguson, Carrie et al.·Respiratory physiology & neurobiology·2025

This study tested whether Long COVID patients experience a measurable drop in exercise capacity after 24 hours, which would suggest their bodies aren't recovering properly from exercise. Researchers had 15 Long COVID patients do exercise tests on two consecutive days and found no significant difference in performance between day 1 and day 2. Surprisingly, this was true even though 80% of patients reported post-exertional malaise (PEM) symptoms over the previous six months.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM unclearObservational

Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome-a clinical pilot study.

Fluge, Øystein, Rekeland, Ingrid Gurvin, Sørland, Kari et al.·Frontiers in medicine·2025

Researchers tested a drug called daratumumab that targets specific immune cells (plasma cells) in 10 ME/CFS patients to see if removing these cells could improve symptoms. Six patients experienced significant improvement in fatigue, physical function, and daily activity levels after treatment, while four showed no major changes. The drug was well-tolerated with no serious side effects, and improvements were sustained over 8-24 months of follow-up.

Immune System

E3 PreliminaryMechanismPEM unclearMechanistic

The potential causes of myasthenia and fasciculations in severely ill ME/CFS patients: the role of disturbed electrophysiology.

Wirth, Klaus J, Steinacker, Jürgen M·Frontiers in physiology·2025

This study proposes that muscle weakness, fatigue, and twitching in severely ill ME/CFS patients may result from a problem with a specific pump in muscle cells called the Na+/K+-ATPase. When this pump doesn't work properly, it allows too much sodium and calcium to build up inside muscle cells, damaging the cell's energy-producing structures (mitochondria) and making muscles weaker and more prone to cramping and involuntary twitching. The researchers suggest this single mechanical problem could explain many of the muscle symptoms severely ill ME/CFS patients experience.

Energy Metabolism

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Quantitative Proteomics on Immune Cells of ME/CFS Patients Using SWATH-MS.

Kumar, Abhishek, Peppercorn, Katie, Kleffmann, Torsten·Methods in molecular biology (Clifton, N.J.)·2025

This study describes a detailed scientific method for examining proteins in immune cells taken from the blood of ME/CFS patients. Researchers used advanced technology called SWATH-MS (a type of mass spectrometry) to identify and measure thousands of proteins at once. The paper explains the step-by-step process they used so that other researchers can use the same method to find protein abnormalities in ME/CFS.

Immune System

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Using the Ratio of Phosphorylated to Non-phosphorylated Forms of Stress Kinase PKR as a Potential Diagnostic Test for ME/CFS.

Sweetman, Eiren, Tate, Warren P·Methods in molecular biology (Clifton, N.J.)·2025

Researchers developed a new blood test that measures a specific immune protein called PKR in white blood cells to help diagnose ME/CFS. The test looks at whether PKR is in an active or inactive form—people with ME/CFS appear to have different patterns of active PKR compared to healthy people. If this method works well in larger studies, it could provide doctors with a simple, quick way to diagnose ME/CFS instead of waiting months while ruling out other illnesses.

Immune System

E3 PreliminaryCommentaryPEM unclearEditorial

Post-infective myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID as two puzzling faces of the same medal. Recent insights.

Chirumbolo, Salvatore, Franzini, Marianno, Tirelli, Umberto·International immunopharmacology·2025

This editorial examines the similarities between ME/CFS (a long-term illness causing extreme fatigue and other symptoms) and post-COVID syndrome (long-term effects some people experience after COVID-19 infection). The authors suggest these two conditions may share common underlying biological mechanisms, even though they arise from different infections. Understanding these connections could help doctors better recognize and treat both conditions.

Long COVID Overlap

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Measurement of Genetic Variations in ME/CFS Patients in the IDO2 Gene Encoding an Enzyme Metabolizing Tryptophan.

Edgar, Christina D, Blair, Anna, Tate, Warren P·Methods in molecular biology (Clifton, N.J.)·2025

This study looked at variations in a specific gene called IDO2 that controls an enzyme involved in breaking down tryptophan, an amino acid in our bodies. The researchers compared how often these genetic variations appear in ME/CFS patients versus healthy people, to see if certain variations might make someone more vulnerable to developing ME/CFS after a triggering event like a viral infection. They developed a straightforward laboratory technique to identify five common mutations in this gene.

Immune System

E3 PreliminaryMechanismPEM not requiredMechanistic

HLA and pathogens in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other post-infection conditions.

Georgopoulos, Apostolos P, James, Lisa M, Peterson, Philip K·Scientific reports·2025

This study explores why some people develop ME/CFS after viral infections while others don't. Researchers looked at immune system genes (HLA types) and tested how well they recognize and fight nine common human herpes viruses. They found that people with certain HLA types have weak immune recognition of these viruses, potentially allowing the viruses to persist and cause ME/CFS, while people with other HLA types have strong recognition and protection.

Immune System

E3 PreliminaryMechanismPEM requiredCase-Control

Large-scale investigation confirms TRPM3 ion channel dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Sasso, Etianne Martini, Er, Teagan S, Eaton-Fitch, Natalie et al.·Frontiers in medicine·2025

This study examined a specific ion channel called TRPM3 in immune cells from people with ME/CFS compared to healthy individuals. Researchers at two different laboratories found that TRPM3 channels work differently in ME/CFS patients—they're less active than in healthy people. Because both labs got the same results independently, this suggests TRPM3 dysfunction could be a reliable biological marker for ME/CFS.

Immune System

E3 PreliminaryCohortPEM requiredCase-Control

The Effect on Quality of Life of Therapeutic Plasmapheresis and Intravenous Immunoglobulins on a Population of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Elevated β-Adrenergic and M3-Muscarinic Receptor Antibodies-A Pilot Study.

Oesch-Régeni, Boglárka, Germann, Nicolas, Hafer, Georg et al.·Journal of clinical medicine·2025

This small pilot study looked at seven ME/CFS patients who had high levels of specific antibodies (proteins the immune system makes) that may harm certain nerve and heart functions. The researchers gave these patients two types of blood-cleaning treatments—plasmapheresis (which filters antibodies out of blood) and immunoglobulins (healthy antibodies)—and tracked their symptoms and quality of life. They found that patients with higher levels of these harmful antibodies tended to report worse quality of life, and the treatments appeared to help reduce both the antibodies and improve how patients felt.

E3 PreliminaryMechanismPEM requiredCross-Sectional

Neurodevelopment Genes Encoding Olduvai Domains Link Myalgic Encephalomyelitis to Neuropsychiatric Disorders.

Arcos-Burgos, Mauricio, Arcos-Holzinger, Mauricio, Mastronardi, Claudio et al.·Diagnostics (Basel, Switzerland)·2025

Researchers compared DNA samples from 77 Australian ME/CFS patients with genetic databases to identify differences that might explain the disease. They found that certain genes involved in brain development—particularly those encoding special protein structures called Olduvai domains—were associated with ME/CFS. When they checked these findings in a separate U.S. patient group, they confirmed several of the same genetic associations, suggesting these genes may play a role in ME/CFS.

E3 PreliminaryMechanismPEM requiredPreprintPreprint

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Che, Xiaoyu, Ranjan, Amit, Guo, Cheng et al.·medRxiv : the preprint server for health sciences·2025

This study found that people with ME/CFS may have an overactive immune system that responds too strongly to germs and infections. The research showed problems with how the body produces energy and manages inflammation, and these problems got worse after exercise in ME/CFS patients but not in healthy people. The findings suggest multiple biological systems are working abnormally in ME/CFS, which could help doctors develop better treatments.

Energy MetabolismImmune SystemPost-Exertional Malaise

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Profiling Antibody Reactivity to Gut Microbes in ME/CFS Patients.

Seton, Katharine A, Carding, Simon R·Methods in molecular biology (Clifton, N.J.)·2025

This study looks at how the immune system of ME/CFS patients reacts to bacteria in the gut. Many ME/CFS patients have changes in their gut bacteria and a leaky gut lining that allows bacteria and their toxic products to enter the bloodstream, potentially triggering widespread inflammation. The researchers developed methods to measure specific immune proteins (antibodies) that ME/CFS patients produce in response to these gut bacteria, compared to healthy household members.

Gut MicrobiomeImmune System

E3 PreliminaryReviewPEM requiredReview-Narrative

Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?

Rahman, A F M Towheedur, Benko, Anna, Bulbule, Sarojini et al.·Biomolecules·2025

This review article examines a molecule called tetrahydrobiopterin (BH4) and its possible role in ME/CFS, particularly in patients who experience orthostatic intolerance (dizziness or fainting when standing up). The researchers found that BH4 metabolism—the way the body processes this molecule—is not working properly in ME/CFS patients with these symptoms. By understanding how BH4 goes wrong, scientists hope to explain why ME/CFS patients have problems with blood flow to the brain.

BiomarkersPost-Exertional Malaise

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Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.

Metabolic adaptation and fragility in healthy 3Din vitroskeletal muscle tissues exposed to chronic fatigue syndrome and Long COVID-19 sera.

Reframing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Biological Basis of Disease and Recommendations for Supporting Patients.

Language Matters: What Not to Say to Patients with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Other Complex Chronic Disorders.

Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome in patients with bipolar affective disorder: A case report.

Advocating the role of trained immunity in the pathogenesis of ME/CFS: a mini review.

Two-day cardiopulmonary exercise testing in long COVID post-exertional malaise diagnosis.

Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome-a clinical pilot study.

The potential causes of myasthenia and fasciculations in severely ill ME/CFS patients: the role of disturbed electrophysiology.

Quantitative Proteomics on Immune Cells of ME/CFS Patients Using SWATH-MS.

Using the Ratio of Phosphorylated to Non-phosphorylated Forms of Stress Kinase PKR as a Potential Diagnostic Test for ME/CFS.

Post-infective myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID as two puzzling faces of the same medal. Recent insights.

Measurement of Genetic Variations in ME/CFS Patients in the IDO2 Gene Encoding an Enzyme Metabolizing Tryptophan.

HLA and pathogens in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other post-infection conditions.

Large-scale investigation confirms TRPM3 ion channel dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

The Effect on Quality of Life of Therapeutic Plasmapheresis and Intravenous Immunoglobulins on a Population of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Elevated β-Adrenergic and M3-Muscarinic Receptor Antibodies-A Pilot Study.

Neurodevelopment Genes Encoding Olduvai Domains Link Myalgic Encephalomyelitis to Neuropsychiatric Disorders.

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Profiling Antibody Reactivity to Gut Microbes in ME/CFS Patients.

Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?

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Metabolism & Mitochondria

Biomarkers

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