ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

481–500 of 742 studies

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 PreliminaryReviewPEM requiredReview-Narrative

Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.

Gupta, Gautam, Buonsenso, Danilo, Wood, John et al.·Comprehensive Physiology·2025

This review examines how Long Covid causes persistent symptoms affecting multiple body systems. The research suggests that SARS-CoV-2 virus may hide in body tissues, trigger ongoing immune problems, and damage how cells produce energy, which could explain fatigue and post-exertion crashes. These mechanisms appear similar to ME/CFS, suggesting the two conditions may share common biological pathways.

NeuroinflammationImmune SystemPost-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

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 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 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 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 PreliminaryMechanismPEM requiredMechanistic

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

Che, Xiaoyu, Ranjan, Amit, Guo, Cheng et al.·npj metabolic health and disease·2025

This study examined blood samples and immune responses in ME/CFS patients to understand why they experience extreme fatigue and feeling worse after activity. Researchers found that patients' immune systems overreact to germs, their bodies have trouble producing energy efficiently, and they have several chemical imbalances in their blood. These problems got worse after exercise and matched how sick patients felt.

Energy MetabolismImmune SystemPost-Exertional Malaise

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 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 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 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 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 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 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 PreliminaryReviewPEM unclearReview-Narrative

Pulmonary Rehabilitation for People With Persistent Symptoms After COVID-19.

Daynes, Enya, Mills, George, Hull, James H et al.·Chest·2024

This review examines whether pulmonary rehabilitation programs—treatments originally designed to help people with chronic lung diseases—might also help people with long COVID who experience breathlessness and fatigue. The authors suggest that because long COVID and chronic lung diseases cause similar problems with breathing and activity tolerance, rehabilitation programs that combine breathing exercises, strength training, and education could be beneficial for long COVID patients. However, they note that special care is needed for people whose symptoms worsen with exercise (postexertional malaise).

Post-Exertional Malaise

E3 PreliminaryDiagnosticPEM requiredMethods-Paper

Assessing Functional Capacity in Myalgic Encephalopathy/Chronic Fatigue Syndrome: A Patient-Informed Questionnaire.

Sommerfelt, Kristian, Schei, Trude, Seton, Katharine A et al.·Journal of clinical medicine·2024

Researchers created a new questionnaire called FUNCAP to measure how much people with ME/CFS can actually do in their daily lives. The tool has two versions: a longer one with 55 questions (for doctors and disability assessments) and a shorter one with 27 questions (for regular check-ups). After testing it with thousands of patients from Norway and around the world, they found it works reliably and accurately captures the impact of ME/CFS on real-life activities.

Post-Exertional Malaise

E3 PreliminaryCohortPEM unclearCase-Control

Circulating microaggregates as biomarkers for the Post-COVID syndrome.

Hermann, M, Lisch, C, Gerth, R et al.·IDCases·2024

This study describes one patient with long COVID who experienced severe fatigue, worsening after exertion, pain, and neurological symptoms. Researchers used a special microscopy technique to examine the patient's blood and found tiny clumps of blood cells and proteins (microaggregates) that shouldn't normally be there. After the patient received blood-thinning medications and antiviral treatment, these clumps dissolved and their symptoms significantly improved.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.

Vu, Luyen Tien, Ahmed, Faraz, Zhu, Hongya et al.·Cell reports. Medicine·2024

Researchers used advanced technology to examine immune cells from ME/CFS patients and healthy controls, both at rest and after exercise. They found that ME/CFS patients have problems with a type of immune cell called monocytes that appear abnormal and may be moving into tissues inappropriately. After exercise, patients showed additional problems with platelets (cells involved in blood clotting), suggesting the disease involves multiple layers of immune system dysfunction.

Immune SystemPost-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

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

Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.

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

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

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

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

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

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

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

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

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

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

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

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

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

Pulmonary Rehabilitation for People With Persistent Symptoms After COVID-19.

Assessing Functional Capacity in Myalgic Encephalopathy/Chronic Fatigue Syndrome: A Patient-Informed Questionnaire.

Circulating microaggregates as biomarkers for the Post-COVID syndrome.

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.

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.

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