ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

461–480 of 737 studies

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 PreliminaryCommentaryPEM requiredEditorial

mTORC1 syndrome (TorS): unifying paradigm for PASC, ME/CFS and PAIS.

Bar-Tana, Jacob·Journal of translational medicine·2025

This study proposes that ME/CFS, Long COVID, and similar post-infection illnesses may all be caused by the same underlying problem: excessive activity of a cellular control system called mTORC1. The authors suggest that if this overactive system is the shared driver of these conditions, it could explain why patients experience fatigue, worsening after exercise, pain, heart rate changes, and brain fog—and it might point toward new treatments.

Energy MetabolismPost-Exertional Malaise

E3 PreliminaryBehavioralPEM unclearObservational

Cognitive behavioural therapy for severe fatigue following COVID-19 in adolescents: a serial single-case observational study of five consecutively referred patients.

Kuut, Tanja A, Müller, Fabiola, Braamse, Annemarie M J et al.·Behavioural and cognitive psychotherapy·2025

This study tested whether cognitive behavioral therapy (CBT)—a type of talk therapy that helps people change unhelpful thinking patterns and behaviors—could help teenagers with severe fatigue after COVID-19. Five teenagers received CBT over 12 weeks. By the end, all five were no longer severely fatigued, most felt less physically limited, and all were able to return to school without absences.

Post-Exertional Malaise

E3 PreliminaryCommentaryPEM requiredEditorial

Complex chronic adverse events following immunization: a systemic critique and reform proposal for vaccine pharmacovigilance.

Kenny, Tiff-Annie·Therapeutic advances in drug safety·2025

This paper describes complex, long-lasting health problems that some people develop after vaccination, which resemble ME/CFS and Long COVID symptoms like fatigue, pain, brain fog, and heart rhythm issues. The author argues that current vaccine safety systems are not well-designed to detect or investigate these kinds of slow-developing, multisystem conditions because they work best for identifying immediate reactions like fever or allergies. The paper proposes changes to how we monitor vaccine safety—including better training for doctors, longer-term tracking of patients, and including patients' own descriptions of their symptoms—to catch these problems more effectively.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Inactivation of ATG13 stimulates chronic demyelinating pathologies in muscle-serving nerves and spinal cord.

Drosen, Molly E, Bulbule, Sarojini, Gottschalk, Gunnar et al.·Immunologic research·2025

Researchers gave mice a drug that overactivates a protein called mTOR and found it triggered muscle weakness, nerve damage, and worsening fatigue after exercise—similar to post-exertional malaise (PEM) in ME/CFS. The drug blocked a cellular cleanup system called autophagy, which led to inflammation and damage to the nerves controlling muscles. Mice engineered to have impaired autophagy showed similar problems, suggesting that broken autophagy may be involved in ME/CFS fatigue and exercise intolerance.

NeuroinflammationPost-Exertional Malaise

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

MyGuide long COVID: An online self-management tool for people with long COVID.

Naik, Hiten, Pongratz, Kyla, Malbeuf, Michelle et al.·Internet interventions·2025

Researchers created MyGuide Long COVID, a free website where people with long COVID answer questions about their symptoms and receive personalized information and self-management tips. The website launched in August 2023 and attracted nearly 8,600 users in its first year, with the most popular topics being post-exertional malaise (worsening symptoms after activity) and general information about long COVID. This shows that a patient-centered online tool developed together with both doctors and people living with long COVID can successfully help patients manage their condition.

Post-Exertional Malaise

E3 PreliminaryGuidelinePEM requiredGuideline

Multidisciplinary collaborative guidance on the assessment and treatment of patients with Long COVID: A compendium statement.

Cheng, Abby L, Herman, Eric, Abramoff, Benjamin et al.·PM & R : the journal of injury, function, and rehabilitation·2025

This is a comprehensive clinical guide created by over 40 Long COVID treatment centers to help doctors evaluate and care for Long COVID patients. The guide covers how to assess symptoms, manage common problems like fatigue and brain fog, and help patients return to work or daily activities. It emphasizes that Long COVID is real, takes it seriously, and recommends treatments based on what doctors currently know while acknowledging many unknowns remain.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredPreprintPreprint

Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis.

Zhang, Sai, Jahanbani, Fereshteh, Chander, Varuna et al.·medRxiv : the preprint server for health sciences·2025

Researchers used advanced artificial intelligence to analyze the genes of ME/CFS patients and discovered 115 genes that may contribute to the disease. They found that people with ME/CFS have lower levels of these risk genes active in their immune cells and nervous system. This genetic analysis could eventually help doctors diagnose ME/CFS more accurately and identify new treatment targets.

BiomarkersImmune SystemCognitive ImpairmentPost-Exertional Malaise

E3 PreliminaryPEM required

Managing Energy, and Shaping Care: Insights from Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Through Co-Production Workshops.

Thornton, Eleanor J, Hayes, Lawrence D, Goodwin, Dawn S et al.·The American journal of medicine·2025

This study asked people with ME/CFS and healthcare providers what they think about managing energy and daily activities. The researchers held online workshops where patients shared their experiences and suggestions for better care. Participants stressed that doctors need better training about ME/CFS, patients should be involved in their own care planning, and new tools like apps and sleep management could help improve how people manage their energy.

Post-Exertional Malaise

E3 PreliminaryDiagnosticPEM requiredMethods-Paper

Stress-Induced Changes in Immune Signatures in ME/CFS Patients Determined by Transcriptome Analysis.

Gamer, Jackson, Van Booven, Derek, Zarnowski, Oskar et al.·Methods in molecular biology (Clifton, N.J.)·2025

Researchers studied how the immune system of ME/CFS patients responds to exercise by examining blood cells before, during, and after a physical challenge. They compared these responses in ME/CFS patients to healthy people using advanced genetic testing. This study is part of ongoing efforts to understand what makes ME/CFS different at a biological level and why exercise can make symptoms worse.

Immune SystemPost-Exertional Malaise

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Developing a minimum dataset for a national patient registry on Long COVID in Canada: a Delphi consensus-based study.

Mazurik, Kathrina, Amah, Adelaide, Dumitrescu, Donna Ioana et al.·BMJ open·2025

Researchers in Canada wanted to create a standard list of questions for a national registry to collect information about Long COVID from patients. They asked 52 experts—including patients, caregivers, doctors, and researchers—to vote on which questions were most important across three rounds of surveys. The final list includes 48 key questions focused on fatigue, post-exertional malaise, heart problems, breathing issues, brain fog, quality of life, and healthcare access.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Exertional Exhaustion (Post-Exertional Malaise, PEM) Evaluated by the Effects of Exercise on Cerebrospinal Fluid Metabolomics-Lipidomics and Serine Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Baraniuk, James N·International journal of molecular sciences·2025

This study examined fluid from around the brain and spinal cord in ME/CFS patients and healthy controls, measuring chemical substances before and after exercise. Researchers found that ME/CFS patients have abnormal levels of certain chemicals related to energy production and brain function, especially after exercise. The study suggests that exercise may trigger harmful changes in brain chemistry in ME/CFS patients that don't happen in healthy people, which could explain post-exertional malaise (the worsening of symptoms after activity).

Post-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Syed, Abu Mohammad, Karius, Alexander K, Ma, Jin et al.·Physiology (Bethesda, Md.)·2025

This review examines how mitochondria—the parts of cells that produce energy—may not be working properly in ME/CFS patients. The authors suggest that problems with energy production in cells could explain why people with ME/CFS feel severely exhausted after physical activity. They also note that similar energy problems appear in long COVID, which suggests both conditions may share a common underlying cause.

Severe MELong COVID OverlapPost-Exertional Malaise

E3 PreliminaryMechanismPEM not requiredObservational

Cytokine profiles associated with persisting symptoms of post-acute sequelae of COVID-19.

Kwon, Ji-Soo, Chang, Euijin, Jang, Hyeon Mu et al.·The Korean journal of internal medicine·2025

After COVID-19, some people develop long-lasting symptoms like fatigue, brain fog, and difficulty exercising—a condition called long COVID or PASC. This study measured immune system markers (called cytokines) in the blood of 79 people and found that certain symptoms were linked to higher levels of specific immune proteins, suggesting the immune system may stay overactive in some long COVID patients.

Immune SystemPost-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Extracellular vesicle proteomics uncovers energy metabolism, complement system, and endoplasmic reticulum stress response dysregulation postexercise in males with myalgic encephalomyelitis/chronic fatigue syndrome.

Glass, Katherine A, Giloteaux, Ludovic, Zhang, Sheng et al.·Clinical and translational medicine·2025

Researchers studied tiny particles called extracellular vesicles in the blood of ME/CFS patients before and after exercise. They found that in people with ME/CFS, these particles show signs of energy problems, immune overactivity, and cellular stress after exertion—changes that were linked to post-exertional malaise (the worsening of symptoms after activity). These findings suggest new targets for treatment that could help improve recovery and energy in ME/CFS.

BiomarkersPost-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise.

Sharma, Sayan, Hodges, Lynette D, Peppercorn, Katie et al.·International journal of molecular sciences·2025

This study looked at how exercise affects the chemical switches on our genes (epigenetics) in ME/CFS patients, particularly during post-exertional malaise (PEM)—the exhaustion that worsens after physical activity. Researchers took blood samples from five ME/CFS patients before, immediately after, and 24-48 hours after an exercise test, and found distinct patterns of genetic changes that were specific to ME/CFS patients and not seen in healthy controls. These changes affected genes related to immune function, inflammation, and blood vessel health, suggesting the body's response to exercise in ME/CFS is fundamentally different at the molecular level.

BiomarkersImmune SystemPost-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID.

Li, Gong-Hua, Han, Fei-Fei, Kalafatis, Efthymios et al.·International journal of molecular sciences·2025

This study found that both ME/CFS and Long COVID may share similar problems with how muscles process certain amino acids (building blocks of proteins). Using computer modeling, researchers identified that two specific metabolic pathways are underactive in muscle tissue. They then tested whether adding supplements containing aspartate and a related compound could help restore normal muscle metabolism, and suggest a combination treatment called LOLA as a potential future therapy.

Post-Exertional Malaise

E3 PreliminaryDiagnosticPEM requiredMethods-Paper

Repeated Cardiopulmonary Exercise Testing of ME/CFS Patients.

Hodges, Lynette·Methods in molecular biology (Clifton, N.J.)·2025

This study explains how doctors use a special exercise test done twice (24 hours apart) to measure how ME/CFS affects the body's ability to exercise. The test shows that people with ME/CFS often cannot exercise as hard the second time, and their bodies don't use oxygen or produce power the way healthy people do. This helps prove that ME/CFS causes real, measurable changes in how the body functions.

Post-Exertional Malaise

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

E3 PreliminaryReviewPEM unclearReview-Narrative

Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options.

Yong, Shin Jie, Kenny, Tiff-Annie, Halim, Alice et al.·Reviews in medical virology·2025

This review describes a condition called post-COVID-19 vaccination syndrome (PCVS), where some people develop long-lasting symptoms similar to long COVID after receiving a vaccine. Symptoms typically start within days to weeks after vaccination and can last for months or years, including fatigue, brain fog, and nerve tingling. The study examines what might cause PCVS and discusses possible treatments, though researchers emphasize that much remains unknown about this condition.

Immune SystemPost-Exertional Malaise

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Evidence Atlas

Evidence browser

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

mTORC1 syndrome (TorS): unifying paradigm for PASC, ME/CFS and PAIS.

Cognitive behavioural therapy for severe fatigue following COVID-19 in adolescents: a serial single-case observational study of five consecutively referred patients.

Complex chronic adverse events following immunization: a systemic critique and reform proposal for vaccine pharmacovigilance.

Inactivation of ATG13 stimulates chronic demyelinating pathologies in muscle-serving nerves and spinal cord.

MyGuide long COVID: An online self-management tool for people with long COVID.

Multidisciplinary collaborative guidance on the assessment and treatment of patients with Long COVID: A compendium statement.

Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis.

Managing Energy, and Shaping Care: Insights from Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Through Co-Production Workshops.

Stress-Induced Changes in Immune Signatures in ME/CFS Patients Determined by Transcriptome Analysis.

Developing a minimum dataset for a national patient registry on Long COVID in Canada: a Delphi consensus-based study.

Exertional Exhaustion (Post-Exertional Malaise, PEM) Evaluated by the Effects of Exercise on Cerebrospinal Fluid Metabolomics-Lipidomics and Serine Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Cytokine profiles associated with persisting symptoms of post-acute sequelae of COVID-19.

Extracellular vesicle proteomics uncovers energy metabolism, complement system, and endoplasmic reticulum stress response dysregulation postexercise in males with myalgic encephalomyelitis/chronic fatigue syndrome.

Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise.

Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID.

Repeated Cardiopulmonary Exercise Testing of ME/CFS Patients.

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

Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options.

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