Evidence browser

DiagnosticsPost-Exertional Malaise

Measures of Overall Illness Severity and Burden for ME/CFS: A Scoping Review.

Cripe, Jada, Ravichandran, Suvetha, Deditz, Samantha et al.·The patient·2026

Researchers reviewed 190 published studies to map out which measurement tools are most commonly used to assess how severe ME/CFS is and how much it impacts patients' daily lives. The most frequently used tools were general health surveys (SF-36 and Sickness Impact Profile) and some disease-specific questionnaires, but the review found that these tools do not consistently measure the same things, and many fail to capture the core experience of post-exertional malaise. The authors conclude that a standardized, ME/CFS-specific measurement approach is needed, though this scoping review does not itself test or validate any new measurement tool.

E0 ConsensusReviewPEM unclearReview-Narrative

[Herbal treatment options for post-viral symptoms and long COVID].

Krassnig, Katharina, Bauer, Rudolf, Glasl, Sabine et al.·Wiener medizinische Wochenschrift (1946)·2026

This review examined herbal medicines and plant-based treatments that may help with long COVID and post-viral symptoms, including ME/CFS. The authors looked at nearly 100 scientific papers and clinical experience to identify which herbs might help with common symptoms like fatigue, brain fog, breathing problems, digestive issues, and loss of smell. They found that several traditional plant remedies appear to help manage these symptoms based on available evidence and doctors' real-world experience.

E0 ConsensusDiagnosticPEM requiredMethods-Paper

Recommended long COVID outcome measures and their implications for clinical trial design, with a focus on post-exertional malaise.

Soares, Letícia, Davis, Hannah, Spier, Ezra et al.·EBioMedicine·2026

This paper provides guidance for researchers designing clinical trials to test treatments for long COVID, with special attention to post-exertional malaise (PEM)—a key symptom where people feel much worse after physical or mental activity. The authors recommend that trials should carefully measure patients at the start, track them over time, include a placebo group for comparison, and make sure patients in different treatment groups have similar severity of illness. The paper highlights that the field urgently needs funding to develop better ways to measure these outcomes before large-scale treatment trials can succeed.

E0 ConsensusGuidelinePEM unclearGuideline

[Psychiatric and psychotherapeutic recommendations for long/post-COVID and ME/CFS: a narrative review of international guidelines].

Kaya, Gizem, Kroehn-Liedtke, Franziska, Kalinowski, Olivia et al.·Der Nervenarzt·2026

This review examined what major international health organizations recommend about mental health care and psychological treatments for ME/CFS and long COVID. The guidelines agree that while mental health support can help manage symptoms, it is not a cure for these conditions. They emphasize the importance of individualized, paced approaches to activity rather than pushing patients to exercise harder, especially when postexertional malaise (worsening after activity) is present.

Chronic fatigue syndrome: From etiology and mechanism to diagnosis and treatment.

Xu, Qing, Zhao, Mengyu, Wang, Qin et al.·Journal of psychiatric research·2026

This review article summarizes current knowledge about ME/CFS, a long-lasting illness characterized by extreme fatigue that rest doesn't improve, along with muscle pain, sore throat, and mood problems. The article examines what might cause ME/CFS, how doctors can better diagnose it, and what treatments may help. The authors note that ME/CFS cases are increasing worldwide, especially since COVID-19, and that current treatments have limited effectiveness.

E0 ConsensusGuidelinePEM unclearGuideline

Clinical practice guideline for long COVID prevention and treatment.

Cao, Bin, Soriano, Joan B, Wang, Quanyi et al.·The European respiratory journal·2026

This guideline summarizes the best available evidence on preventing and treating long COVID (also called post-COVID syndrome). A large international team of experts reviewed research studies and patient experiences to create 10 practical recommendations for doctors. The main suggestions include using vaccines or antivirals early during acute COVID infection to prevent long COVID, avoiding certain medications that don't help, and recommending probiotics, cognitive behavioral therapy for fatigue, and rehabilitation as helpful treatments.

E0 ConsensusReviewPEM requiredSystematic-Review

Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review.

Kim, Do-Young, Youn, Jaeyoung, Kang, Naeun et al.·Journal of translational medicine·2026

This study looked at how treating the connection between the brain and gut might help people with ME/CFS and Long COVID. Researchers reviewed eight previous studies testing different treatments—including special nerve stimulation and probiotics—and also followed one patient who improved with a type of needle stimulation. Many of these treatments showed promise in reducing fatigue and post-exertional malaise, possibly by helping restore healthy gut bacteria and reduce brain inflammation.

NeuroinflammationPost-Exertional Malaise

E0 ConsensusReviewPEM unclearReview-Narrative

[Post-COVID: An inventory focusing on the key complaints PEM and POTS].

Hensel, Ole, Pfrommer, Laura, Furch, Peggy et al.·MMW Fortschritte der Medizin·2026

This is a narrative review (a summary of existing research rather than a new study) that examined long-term effects of COVID-19, with a focus on post-exertional malaise (PEM) and postural tachycardia syndrome (POTS). The authors report that in people with post-COVID, PEM—a worsening of symptoms after exertion—was observed in approximately 86% of patients, and POTS-related symptoms in up to 82%. The review suggests pacing and symptom-focused treatments may help, though these are early findings from a narrative synthesis rather than definitive evidence.

InterventionsAutonomic Nervous SystemDiagnosticsLong COVID Overlap

E0 ConsensusReviewPEM requiredEditorial

Myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia - overlap, differences, and emerging insights.

Murovska, Modra, Krumina, Angelika, Araja, Diana et al.·Journal of translational medicine·2026

ME/CFS and fibromyalgia are two different but often overlapping illnesses that cause severe fatigue, pain, and other debilitating symptoms. While they share many similarities, ME/CFS has a distinctive feature called post-exertional malaise—where activity makes symptoms dramatically worse for hours or days—while fibromyalgia does not. This review shows that the two conditions have different immune system patterns and may require different treatment approaches.

Severe MEImmune SystemCognitive ImpairmentPost-Exertional Malaise

E0 ConsensusReviewPEM unclearReview-Narrative

Physiotherapy management of Long-COVID: an evidence-based approach.

Reeves, Jack, Daynes, Enya, Janaudis-Ferreira, Tania et al.·Brazilian journal of physical therapy·2026

This guideline describes how physiotherapists can manage Long-COVID using evidence-based approaches. The recommendations include assessment of fatigue, post-exertional malaise, breathing problems, cognitive symptoms, and orthostatic intolerance, followed by tailored management such as pacing, energy conservation, breathing retraining, and return-to-work planning. The authors emphasise the importance of validating patient experiences and individualising care, though the evidence base for these specific approaches in Long-COVID remains under development.

InterventionsAutonomic Nervous SystemCognitive ImpairmentPost-Exertional Malaise

InterventionsSleepPost-Exertional Malaise

The efficacy of exercise in patients with myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and meta-analysis.

Zhao, Liping, Gou, Bo, Zhang, Meng·Journal of psychosomatic research·2026

A systematic review of 17 randomized controlled trials (involving 1,944 patients) found that exercise was associated with reported improvements in fatigue, sleep quality, quality of life, depression, and anxiety in ME/CFS patients. However, exercise did not show significant benefits for heart and lung function or overall physical capacity. The review noted no major differences in safety or tolerability between exercise and control groups, though individual responses vary and respecting personal energy limits is emphasized.

NeuroinflammationEnergy MetabolismImmune SystemCognitive Impairment

Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.

Jin, Hongjiao, An, Yi, Huang, Jingwei et al.·Frontiers in immunology·2026

This systematic review proposes a framework for understanding post-exertional malaise (PEM)—the worsening of symptoms after mild activity—by examining how energy production, immune activation, and brain inflammation may be associated with each other in people with Long COVID and chronic fatigue conditions. The authors suggest that in vulnerable individuals, exercise may trigger an abnormal cascade involving damaged mitochondria (cellular energy factories), inflammatory molecules, and changes in how the brain perceives fatigue and pain. However, this is a theoretical model based on existing literature; individual mechanisms have not been directly tested in a single study.

E0 ConsensusReviewPEM unclearMeta-Analysis

Neuroendocrine signature of ME/CFS: Meta-analytic evidence for bioactive cortisol deficit and exaggerated feedback sensitivity.

Woo, Tae-Wook, Choi, Yu-Jin, Kim, Jun-Yeol et al.·Molecular psychiatry·2026

A review of 46 studies involving 1,388 ME/CFS patients found that people with ME/CFS were observed to have lower cortisol (a stress hormone) measured in saliva, urine, and hair, and showed altered responses when given hormone-stimulation tests. The authors propose these findings may be associated with some ME/CFS symptoms like fatigue and sleep problems, though the clinical significance and how this relates to individual patient outcomes remains unclear.

Endocrine DisruptionBiomarkersSleepCognitive Impairment

Immune SystemPost-Exertional Malaise

Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Van Campenhout, Jente, Buntinx, Yanthe, Xiong, Huan-Yu et al.·Biomolecules·2025

This review examines how ME/CFS might involve two connected problems: the body's cells not producing enough energy, and the immune system not working properly. The authors suggest that when cells can't make enough energy, this might directly weaken the immune system, which could explain why patients experience severe fatigue and feel worse after physical activity. The review proposes that treatments targeting both energy production and immune function together might help patients more effectively than treating either problem alone.

BiomarkersPost-Exertional Malaise

Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia.

Davis, Leah, Higgs, Maisy, Snaith, Ailsa et al.·Frontiers in neuroscience·2025

This review examined research showing that ME/CFS, Gulf War Syndrome, and fibromyalgia may share similar problems with how the body produces energy and handles stress at the cellular level. Scientists found that these three conditions show signs of disrupted fat metabolism, energy production difficulties, and increased cellular damage from oxidative stress. Better understanding these shared biological problems could help doctors diagnose these conditions faster and develop treatments that target the root causes rather than just treating symptoms.

NeuroinflammationEnergy MetabolismImmune SystemPost-Exertional Malaise

Insights into the Complex Biological Network Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Dudova, Dobrina, Bozhkova, Martina, Petrov, Steliyan et al.·International journal of molecular sciences·2025

This review brings together research showing that ME/CFS involves multiple body systems going wrong at the same time—including problems with the immune system, energy production in cells, hormone balance, and gut health. These problems appear to feed into each other, creating a cycle that keeps the illness going. The findings suggest ME/CFS is not just one thing breaking down, but rather many interconnected systems all struggling together.

Assessment of symptoms in myalgic encephalomyelitis/chronic fatigue syndrome: a comparative study of existing scales.

Lu, Jing, Sun, Weibo, Li, Shulin et al.·Frontiers in neurology·2025

This review examined the different questionnaires and tests doctors use to measure ME/CFS symptoms. The researchers looked at how well these tools work for diagnosing the illness and tracking how patients change over time. They found that while current tests are reasonably reliable, we need better tools that measure all the different ways ME/CFS affects people—like fatigue, brain fog, pain, and sleep problems—in a more consistent and objective way.

Gut MicrobiomeImmune SystemPost-Exertional Malaise

Gut Microbiome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Insights into Disease Mechanisms.

Nikolova, Ralitsa, Donchev, Deyan, Vaseva, Katya et al.·International journal of molecular sciences·2025

This review examines the connection between gut bacteria and ME/CFS, a condition characterized by exhaustion that worsens after activity. The authors explain how an imbalance in gut bacteria may damage the intestinal barrier, allowing bacterial particles to enter the bloodstream and trigger inflammation throughout the body. They also discuss how changes in gut bacteria might affect the brain, contributing to the brain fog and cognitive problems many ME/CFS patients experience.

E0 ConsensusReviewPEM unclearEvidence-Map

Recent research in myalgic encephalomyelitis/chronic fatigue syndrome: an evidence map.

Todhunter-Brown, Alex, Campbell, Pauline, Broderick, Cathryn et al.·Health technology assessment (Winchester, England)·2025

This study looked at all ME/CFS research published between 2018 and 2023 to see what scientists have been studying and how much research exists on different topics. Researchers found 639 studies involving over 600,000 people with ME/CFS. More than half of the research focused on trying to understand what causes ME/CFS, while fewer studies looked at treatments or how to diagnose the condition. The researchers created an interactive map so patients and doctors can explore what research has been done.

Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome.

Haunhorst, Simon, Dudziak, Diana, Scheibenbogen, Carmen et al.·Infection·2025

This review examines why people with ME/CFS and long COVID feel much worse after physical activity—a condition called post-exertional malaise. The researchers found that when these patients exercise, their bodies struggle to use oxygen properly and produce energy efficiently, likely due to problems with tiny blood vessels and lingering immune activation. This causes a buildup of harmful substances like lactate and triggers further inflammation and exhaustion.