ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

481–500 of 737 studies

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 PreliminaryCohortPEM unclearCross-Sectional

Patient Perspectives on the Care in a Long COVID Outpatient Clinic-A Regional Qualitative Analysis from Germany.

Gölz, Lea Alexandra, Poß-Doering, Regina, Merle, Uta et al.·Healthcare (Basel, Switzerland)·2025

Researchers interviewed 14 patients attending a specialized Long COVID clinic in Germany to understand their experiences with care. Patients reported that while the clinic staff were knowledgeable and compassionate, many experienced a worsening of symptoms after their visit (a pattern called post-exertional malaise), and most wanted more follow-up appointments to manage their condition.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM not requiredMechanistic

Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation.

Jothi, Swathi, Insel, Michael, Claessen, Guido et al.·Physiological reports·2025

This study compared how bodies use oxygen during exercise in people with long COVID, ME/CFS, and healthy controls. Researchers found that both long COVID and ME/CFS patients had trouble getting oxygen into their muscles during exercise, which was the main reason they couldn't exercise as much as healthy people. If this muscle oxygen problem could be fixed, it might significantly improve exercise ability in both conditions.

Post-Exertional Malaise

E3 PreliminaryDiagnosticPEM requiredMethods-Paper

Measuring Biomarkers of Oxidative Stress in ME/CFS Patients.

Walker, Max·Methods in molecular biology (Clifton, N.J.)·2025

This study looked at whether certain molecules in the blood and immune cells could show signs of oxidative stress (cellular damage from harmful molecules called free radicals) in ME/CFS patients. The researchers tested two different markers before and after exercise: one test successfully measured protein damage, while another test designed to measure DNA damage was not sensitive enough to detect changes in this patient group.

BiomarkersPost-Exertional Malaise

E3 PreliminaryMechanismPEM not requiredMechanistic

Jingfang Granule promotes the tricarboxylic acid cycle to improve chronic fatigue syndrome by increasing the expression of Idh1 and Idh2.

Wang, Kun, Shen, Mengmeng, Tang, Hongguang et al.·Journal of ethnopharmacology·2025

Researchers tested a traditional Chinese medicine called Jingfang Granule (JFG) in mice with chronic fatigue syndrome. The treatment improved fatigue symptoms, helped mice recover weight and exercise capacity, and reduced harmful inflammation and oxidative stress in their bodies. The medicine appeared to work by boosting how efficiently cells produce energy through a key metabolic pathway.

Post-Exertional Malaise

E3 PreliminaryCohortPEM requiredCase-Control

Multimodal Telerehabilitation in Post COVID-19 Condition Recovery: A Series of 12 Cases.

Carpallo-Porcar, Beatriz, Beamonte, Esther Del Corral, Jiménez-Sánchez, Carolina et al.·Reports (MDPI)·2025

This study tested whether people recovering from COVID-19 could improve their symptoms through home-based exercise and education delivered via video appointments over 12 weeks. Most patients improved in fatigue, exercise capacity, and muscle strength, though breathlessness did not improve as much. The results suggest that remote rehabilitation programs delivered from home may be helpful for people with long COVID symptoms.

Post-Exertional Malaise

E3 PreliminaryPEM required

Glymphatic System Dysregulation as a Key Contributor to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Nemat-Gorgani, Mohsen, Jensen, Michael Anthony, Davis, Ronald Wayne·International journal of molecular sciences·2025

Your brain has a cleaning system called the glymphatic system that removes toxic waste buildup, especially during sleep. This review suggests that this cleaning system may not be working properly in ME/CFS, which could explain symptoms like fatigue and brain fog. If the glymphatic system is involved in ME/CFS, new treatments designed to fix this cleaning process might help patients feel better.

SleepPost-Exertional Malaise

E3 PreliminaryCommentaryPEM unclearEditorial

Skeletal muscle adaptations and post-exertional malaise in long COVID.

Charlton, Braeden T, Goulding, Richie P, Jaspers, Richard T et al.·Trends in endocrinology and metabolism: TEM·2025

This article reviews evidence that long COVID symptoms—especially worsening after activity (post-exertional malaise)—may be caused by problems with how muscles produce energy, damage to blood vessel function, and changes in muscle fiber types that make them rely more on less-efficient energy pathways. The authors suggest that physical or mental exertion may trigger rapid muscle damage and immune cell infiltration, which could explain why patients feel worse after activity.

Post-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 requiredMechanistic

Post-exertional malaise - A functional brain aberration?

Bruun Bratholm Wyller, Vegard·Brain, behavior, and immunity·2024

This study explores whether post-exertional malaise (PEM)—the hallmark symptom of ME/CFS where activity makes symptoms worse—might be caused by problems in how the brain functions. Researchers examined brain activity patterns in ME/CFS patients to understand what happens after exertion. The findings suggest that brain function abnormalities could play a role in why patients experience this debilitating symptom.

Post-Exertional Malaise

E3 PreliminaryCohortPEM unclearCase-Control

Acute Compartment Syndrome and Rhabdomyolysis Caused by a Single Electrical Muscle Stimulation in a 46-Year-Old Female Professional Athlete With Fibromyalgia, Chronic Fatigue Syndrome, and Myofascial Disorder: A Case Report.

von Deneen, Karen M, Alemayehu, Dereje Gobena, Khosla, Ajit·Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine·2024

This case report describes a 46-year-old female athlete with ME/CFS and fibromyalgia who experienced a serious muscle injury called rhabdomyolysis after just one session of electrical muscle stimulation (EMS) training. Her muscles broke down severely enough to cause compartment syndrome—a dangerous swelling in the muscle tissue—requiring intensive hospital care with fluids and medications. The report warns that people with ME/CFS and similar chronic conditions should be very cautious with EMS training because their bodies may react more severely to this type of exercise.

Post-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

[Myalgic encephalomyelitis/chronic fatigue syndrome as a complication of COVID-19 post-acute syndrome in adults. Bibliographic Review].

Carrillo Uguña, Miguel Esteban, Orellana Romero, Paula Michelle·Vertex (Buenos Aires, Argentina)·2024

This review examines how some COVID-19 survivors develop symptoms very similar to ME/CFS weeks or months after their acute infection ends. The authors found that over 87% of COVID-19 patients still experience at least one symptom two months after infection, and some of these symptoms match what ME/CFS patients experience. The study suggests that COVID-19 may trigger ME/CFS-like illness in some adults, similar to how other infections have been linked to ME/CFS in the past.

Long COVID OverlapPost-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

Functional neurological disorder, physical activity and exercise: What we know and what we can learn from comorbid disorders.

Boylan, Kelly A, Dworetzky, Barbara A, Baslet, Gaston et al.·Epilepsy & behavior reports·2024

This review examines how exercise and physical activity might help people with functional neurological disorder (FND), a condition that causes neurological symptoms without a clear structural brain abnormality. The authors note that FND often occurs alongside other conditions like ME/CFS, fibromyalgia, and POTS, and they suggest that problems with the autonomic nervous system (which controls automatic body functions) may underlie these conditions. By looking at research on exercise in related disorders, they explore how physical activity might help regulate the nervous system and reduce symptoms.

Post-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

Long Covid.

Zaidi, Asiya Kamber, Dehgani-Mobaraki, Puya·Progress in molecular biology and translational science·2024

Long COVID is a condition where people experience ongoing symptoms weeks or months after having COVID-19. This review examines what might cause Long COVID, including lingering virus in the body, problems with the immune system, and issues with blood vessels and nerves. The authors discuss how doctors can recognize and treat Long COVID, emphasizing that patients often need care from multiple specialists working together.

Immune SystemPost-Exertional Malaise

E3 PreliminaryCohortPEM requiredCase-Control

Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19.

McAlpine, Lindsay, Zubair, Adeel S, Joseph, Phillip et al.·Neurology(R) neuroimmunology & neuroinflammation·2024

This study looked at 16 patients who developed nerve damage in their small nerves after COVID-19. The researchers found that 92% of these patients also had symptoms of ME/CFS, including post-exertional malaise (feeling much worse after activity). When 9 patients were treated with IVIG (an immune therapy), all of them improved significantly, while only 3 out of 7 untreated patients improved.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredCross-Sectional

A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation.

Kaur, Raminder, Greeley, Brian, Ciok, Alexander et al.·Medicina (Kaunas, Lithuania)·2024

Researchers used two advanced brain imaging techniques together to look for differences between people with ME/CFS and healthy people. The study found specific changes in brain chemistry and activity patterns in ME/CFS patients, particularly in areas related to thinking and fatigue control. The imaging was safe and didn't make patients immediately more fatigued, suggesting these techniques could be useful for studying ME/CFS in the future.

Post-Exertional Malaise

E3 PreliminaryCommentaryPEM requiredEditorial

Attenuating post-exertional malaise in Myalgic encephalomyelitis/chronic fatigue syndrome and long-COVID: Is blood lactate monitoring the answer?

Faghy, Professor Mark A, Ashton, Dr Ruth Em, McNelis, Mr Robin et al.·Current problems in cardiology·2024

This editorial discusses whether measuring blood lactate levels could help manage post-exertional malaise (PEM)—the debilitating fatigue that occurs after physical activity in ME/CFS and long-COVID patients. The authors suggest that blood lactate monitoring might help identify safe exercise limits and prevent PEM crashes. However, this is an opinion piece rather than a research study with new data.

BiomarkersPost-Exertional Malaise

E3 PreliminaryMechanismPEM requiredCross-Sectional

Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise.

Giloteaux, Ludovic, Glass, Katherine A, Germain, Arnaud et al.·Journal of extracellular vesicles·2024

When people without ME/CFS exercise, their bodies release tiny particles called extracellular vesicles that help cells communicate and recover. This study found that in people with ME/CFS, these particles carry different proteins after exercise compared to healthy people, and these differences match how severe a person's symptoms are. This suggests that ME/CFS patients' bodies may have a distinct biological response to exercise that could explain why exertion makes their symptoms worse.

BiomarkersPost-Exertional Malaise

E3 PreliminaryReviewPEM requiredReview-Narrative

[Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept].

Luchting, Benjamin, Behrends, Uta, Eigner, Bianca et al.·Schmerz (Berlin, Germany)·2024

Standard pain therapy programs often push patients to gradually increase their activity levels, but this approach can be harmful for people with ME/CFS because of postexertional malaise (PEM)—a worsening of symptoms after physical or mental effort. This paper reviews how pain therapy should be redesigned specifically for ME/CFS patients and presents a new model clinic program that carefully adjusts treatment to each person's individual tolerance levels to avoid triggering symptom flares.

Post-Exertional Malaise

E3 PreliminaryCohortPEM requiredCase-Control

Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein-Barr Virus.

Tang-Siegel, Gaoyan G, Maughan, David W, Frownfelter, Milah B et al.·Case reports in genetics·2024

This study describes one patient with ME/CFS whose symptoms began after a severe viral infection (Epstein-Barr virus, which causes mononucleosis) 24 years ago. Researchers found that her cells had genetic mutations affecting the mitochondria—the 'power plants' that produce energy for our bodies—which may explain her extreme fatigue and difficulty recovering from physical activity. The study also found abnormal mitochondria circulating in her blood, suggesting that energy production problems may be contributing to her ME/CFS symptoms.

Post-Exertional Malaise

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Evidence Atlas

Evidence browser

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

Patient Perspectives on the Care in a Long COVID Outpatient Clinic-A Regional Qualitative Analysis from Germany.

Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation.

Measuring Biomarkers of Oxidative Stress in ME/CFS Patients.

Jingfang Granule promotes the tricarboxylic acid cycle to improve chronic fatigue syndrome by increasing the expression of Idh1 and Idh2.

Multimodal Telerehabilitation in Post COVID-19 Condition Recovery: A Series of 12 Cases.

Glymphatic System Dysregulation as a Key Contributor to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Skeletal muscle adaptations and post-exertional malaise in long COVID.

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

Post-exertional malaise - A functional brain aberration?

Acute Compartment Syndrome and Rhabdomyolysis Caused by a Single Electrical Muscle Stimulation in a 46-Year-Old Female Professional Athlete With Fibromyalgia, Chronic Fatigue Syndrome, and Myofascial Disorder: A Case Report.

[Myalgic encephalomyelitis/chronic fatigue syndrome as a complication of COVID-19 post-acute syndrome in adults. Bibliographic Review].

Functional neurological disorder, physical activity and exercise: What we know and what we can learn from comorbid disorders.

Long Covid.

Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19.

A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation.

Attenuating post-exertional malaise in Myalgic encephalomyelitis/chronic fatigue syndrome and long-COVID: Is blood lactate monitoring the answer?

Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise.

[Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept].

Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein-Barr Virus.

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