ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

441–460 of 729 studies

E3 PreliminaryReviewPEM requiredReview-Narrative

Lactate, Capnia, and Fat Oxidation as Therapeutic Axes for SARS-CoV-2 Spike Protein-Induced Sequelae.

Gracidas, Carlos, Levy, Rakeem, Varon, Joseph et al.·Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme·2026

This review suggests that ME/CFS and long COVID symptoms—including exhaustion, brain fog, and crashing after activity—may be caused by problems with how the body's energy-producing structures (mitochondria) work. The authors propose that treatments targeting three areas could help: improving the body's ability to handle lactate (a byproduct of exertion), increasing oxygen delivery to tissues, and helping the body burn fat for energy more efficiently, similar to how endurance athletes train.

Post-Exertional Malaise

E3 PreliminaryCommentaryPEM not requiredEditorial

An Overview of Severe Myalgic Encephalomyelitis.

Vink, Mark, Vink-Niese, Alexandra·Journal of clinical medicine·2026

This article reviews what we know about severe ME/CFS, a serious illness that can leave people completely bedbound and dependent on caregivers. Currently, there is no blood test or scan that can diagnose ME/CFS, though a special two-day exercise test can help document the problem. The authors emphasize that severe ME/CFS is a major medical condition that has received very little research funding, and there are currently no proven treatments available.

Severe MEPost-Exertional Malaise

E3 PreliminaryReviewPEM requiredReview-Narrative

Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system.

Nunes, Massimo, Kell, Loren, Slaghekke, Anouk et al.·Cell death & disease·2026

This study proposes that ME/CFS and long COVID may be caused by damage to the blood vessels (endothelial cells) that occurs after a viral infection. When these cells become damaged and 'senescent' (aged), they release harmful substances that cause inflammation, blood clots, and reduced blood flow to the brain and other organs. The study suggests that a faulty immune system keeps these damaged blood vessels from healing, which is why symptoms persist for months or years after the initial infection.

Immune SystemPost-Exertional Malaise

E3 PreliminaryCohortPEM requiredCase-Control

Resolution of Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome symptoms following kanshoho, a low-pressure muscle relaxation technique: A case report.

Amitani, Haruka, Sakato, Takashi, Asakawa, Akihiro·Explore (New York, N.Y.)·2026

A woman with Long COVID and ME/CFS who had severe fatigue, pain, brain fog, and sleep problems tried a gentle hands-on relaxation technique called kanshoho along with activity pacing advice. After 10 treatment sessions over 2.5 months, her symptoms completely resolved, and she was able to stop her antidepressant medication without symptom worsening. While this is just one person's experience, it suggests this low-pressure approach might help some ME/CFS patients who cannot tolerate exercise-based treatments.

Post-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 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 requiredMechanistic

Gulf War Illness Induced Sex-Specific Transcriptional Differences Under Stressful Conditions.

Frank, Joshua, Tehrani, Lily, Gamer, Jackson et al.·International journal of molecular sciences·2025

Researchers studied how the immune system responds to physical stress in Gulf War veterans with Gulf War Illness (GWI), a condition similar to ME/CFS with fatigue, brain fog, and exhaustion. They found that men and women with GWI have different patterns of immune system activation during and after exercise, suggesting their bodies handle stress differently. These differences could help doctors develop better tests and treatments tailored to each person's sex.

BiomarkersImmune SystemPost-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 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 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 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 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 PreliminaryMechanismPEM requiredMechanistic

Uncovering the genetic architecture of ME/CFS: a precision approach reveals impact of rare monogenic variation.

Birch, Camille L, Wilk, Brandon M, Gajapathy, Manavalan et al.·Journal of translational medicine·2025

Researchers studied the DNA of 31 people with ME/CFS from 25 families to find genetic causes of the illness. They found that about 39% of participants had gene mutations that could contribute to ME/CFS, and these mutations affected how bodies produce energy and handle stress. While the specific genes varied between patients, they all seemed to affect similar biological pathways, suggesting ME/CFS may be caused by different genetic problems that lead to the same symptoms.

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 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 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 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 PreliminaryBehavioralPEM requiredCase-Control

Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report.

Kurotori, Isaku, Sasao, Wataru, Abe, Masahiko·PCN reports : psychiatry and clinical neurosciences·2025

This case report describes a 65-year-old woman who developed ME/CFS symptoms after receiving her third COVID-19 vaccine, including severe tiredness, worsening after activity, and dizziness. After 30 months of symptoms, she recovered using a combination approach that included careful activity management, medications, and mental health support. This is the first documented case showing full recovery from vaccine-associated ME/CFS.

Post-Exertional Malaise

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Lactate, Capnia, and Fat Oxidation as Therapeutic Axes for SARS-CoV-2 Spike Protein-Induced Sequelae.

An Overview of Severe Myalgic Encephalomyelitis.

Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system.

Resolution of Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome symptoms following kanshoho, a low-pressure muscle relaxation technique: A case report.

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

Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Gulf War Illness Induced Sex-Specific Transcriptional Differences Under Stressful Conditions.

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

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

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

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

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.

Uncovering the genetic architecture of ME/CFS: a precision approach reveals impact of rare monogenic variation.

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.

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

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

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

Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report.

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