Evidence browser

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.

NeuroinflammationPain and SensitizationBiomarkersImmune System

Clinical applications of epigenetic signatures in chronic pain management and health outcome prediction.

Ben Amar, Jinane, Michiels, Joni, Hendrix, Jolien et al.·Epigenomics·2026

This review examined how epigenetic changes—chemical switches that turn genes on and off without altering DNA itself—are observed in chronic pain conditions including fibromyalgia and ME/CFS. Researchers found that alterations in DNA methylation and other epigenetic marks are associated with inflammation, pain signaling, and sensitization pathways. The review suggests that epigenetic markers may one day help identify people at risk or predict outcomes, though these applications remain preliminary and require further development.

E0 ConsensusReviewPEM not requiredMeta-Analysis

Risks of autoimmune and inflammatory post-acute COVID-19 conditions: a network cohort study in six European countries, the USA and Korea.

Burkard, Theresa Ms, López-Güell, Kim, Català, Martí et al.·BMJ public health·2026

This large study looked at whether people who had COVID-19 were more likely to develop autoimmune or inflammatory conditions—including ME/CFS and POTS—in the 9 months after infection. Researchers examined health records from over 2.5 million people across eight countries and did not observe increased rates of these conditions in COVID-19 patients compared to people who tested negative. However, the findings do not yet tell us whether similar patterns apply to ME/CFS specifically, and the study was observational rather than experimental.

Autonomic Nervous SystemImmune SystemLong COVID Overlap

Gut MicrobiomeAutonomic Nervous SystemDiagnosticsImmune System

Association between myalgic encephalomyelitis/chronic fatigue syndrome and irritable bowel syndrome: a systematic review and meta-analysis.

Rajabi, Natalie, Ramdass, Prakash V A K·Frontiers in medicine·2026

A new systematic review combined data from 22 studies to examine how often irritable bowel syndrome (IBS) and ME/CFS occur together. Researchers reported that people with ME/CFS were substantially more likely to also have IBS compared to people without ME/CFS, and that about 37% of people with ME/CFS in these studies had IBS. However, the results varied considerably depending on which diagnostic criteria were used to define ME/CFS, suggesting uncertainty about the true overlap.

Exercise interventions for physical function, psychological health, and quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and network meta-analysis.

Gao, Jiawen, Liu, Yunyang, Wang, Shun et al.·Journal of psychosomatic research·2026

This study looked at 57 different research trials involving over 4,200 patients with ME/CFS and fibromyalgia to find out which types of exercise work best. The researchers found that different exercises help with different symptoms: combined exercise and high-intensity interval training (HIIT) are best for improving physical fitness and quality of life, aerobic exercise and combined exercise help most with anxiety and depression, and aquatic (water-based) exercise works best for pain relief. The type of exercise matters much more than how often or how long you do it.

E0 ConsensusReviewPEM not requiredMeta-Analysis

Use of artificial intelligence and machine learning for the management of fibromyalgia: a scoping review.

Clempi Almeida E Silva, Ana Laura, Reis, Victor Hugo Palhares Flávio, Lamoglia, Antonieta Santos Andrade et al.·The Journal of manual & manipulative therapy·2026

This review looked at 43 studies from 2011–2024 to see how artificial intelligence (AI) and machine learning can help diagnose fibromyalgia and other conditions like ME/CFS. Researchers found that AI tools can identify unique patterns in brain scans, genes, eye imaging, and blood markers that differ between sick patients and healthy people. While some AI models showed very high accuracy (up to 100%), most studies tested only small groups of patients, so we need bigger, more rigorous research before these tools can be used reliably in clinics.

Diagnostics

Emotional and behavior problems in children and adolescents with chronic physical health conditions: an updated meta-analysis.

Pinquart, Martin·Journal of pediatric psychology·2026

This study looked at 1,337 research papers to understand how children with long-term health conditions—including chronic fatigue syndrome (ME/CFS)—experience emotional and behavioral challenges. Children with these conditions had higher rates of anxiety, depression, and behavior problems compared to healthy peers. The study found that parents reported more problems than teenagers themselves did, and that ME/CFS was particularly linked to emotional difficulties.

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.

InterventionsDiagnosticsCognitive Impairment

Digital Approaches for Managing Brain Fog in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Interventions, Monitoring, and Future Directions.

Araja, Diana, Murovska, Modra, Krumina, Angelika et al.·Life (Basel, Switzerland)·2026

This review examined how digital tools—such as apps and online platforms—might help people with ME/CFS monitor and manage 'brain fog', a common cognitive difficulty patients report. The authors found that while some digital assessment tools show promise, most approaches for using technology to help with brain fog remain under-studied and limited in evidence. Digital monitoring and rehabilitation approaches are less well-established than cognitive assessment tools.

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

Evaluating working memory functioning in individuals with myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review and meta-analysis.

Penson, Maddison, Kelly, Kate·Psychology, health & medicine·2026

This study reviewed 34 research papers to understand how ME/CFS affects working memory—the ability to hold and use information in your mind briefly. The researchers found that people with ME/CFS have significant difficulties with verbal working memory (remembering words and language), but their ability to remember visual information (like images or patterns) appeared similar to people without ME/CFS. This suggests that cognitive problems in ME/CFS may affect certain types of thinking more than others.

Cognitive Impairment

Systematic literature review: treatment of postural orthostatic tachycardia syndrome (POTS).

Schiweck, Nicole, Langer, Katharina, Maier, Andrea et al.·Clinical autonomic research : official journal of the Clinical Autonomic Research Society·2026

This review examined treatments for POTS (postural orthostatic tachycardia syndrome), a condition where your heart rate jumps significantly when you stand up, causing dizziness and fatigue. POTS is common in people with ME/CFS. The researchers looked at 45 studies and found that simple first-line treatments like compression socks, physical training, extra salt, and a vagus nerve stimulation device may help, while certain medications like ivabradine and beta-blockers also showed promise in some studies.

Autonomic Nervous System

[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 ConsensusReviewPEM requiredSystematic-Review

The search for a blood-based biomarker for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): from biochemistry to electrophysiology.

Clarke, Krista S P, Kingdon, Caroline C, Hughes, Michael Pycraft et al.·Journal of translational medicine·2025

This review looked at recent research on finding a simple blood test that could definitively diagnose ME/CFS, which currently takes years and relies on ruling out other diseases. Scientists have found several promising approaches—including measuring immune cell properties, checking how blood cells respond to stress, and detecting metabolic changes—that show they can tell ME/CFS patients apart from healthy people and others with different illnesses. However, these tests need more testing in larger groups and practical refinement before doctors can use them in everyday care.

E0 ConsensusReviewPEM requiredSystematic-Review

Health-related quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: a systematic review.

Weigel, Breanna, Inderyas, Maira, Eaton-Fitch, Natalie et al.·Journal of translational medicine·2025

This review looked at 16 research studies comparing how ME/CFS and long COVID affect people's quality of life compared to healthy people. The findings show that both conditions severely impact physical health, daily activities, work, and pain levels. People with these illnesses struggle significantly more than healthy individuals across all areas of life, highlighting the urgent need for better support services and disability recognition.

E0 ConsensusReviewPEM not requiredSystematic-Review

Comparative efficacy of various exercise therapies for chronic fatigue syndrome: A systematic review and network meta-analysis.

Liao, Zhongxin, Zhao, Suhong, Fang, Sitong et al.·iScience·2025

Researchers reviewed 25 studies testing different types of exercise for ME/CFS to see which worked best. Graded exercise therapy (GET)—where activity is slowly increased over time—showed the most short-term improvement in fatigue, mood, and anxiety compared to no treatment. Other exercises like yoga, qigong, and strength training showed smaller benefits that may not be meaningful for most patients.

E0 ConsensusReviewPEM not requiredReview-Narrative

The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review.

Hsu, Chou-Yi, Ahmad, Irfan, Maya, Rana Warid et al.·Journal of translational medicine·2025

This review looked at how gut health might be connected to ME/CFS and found that people with ME/CFS often have different bacteria in their gut compared to healthy people. The researchers reviewed studies about various gut-focused treatments like probiotics, dietary changes, and other interventions that might help reduce ME/CFS symptoms by improving the gut-brain connection.

Gut Microbiome

A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome.

Morse, Brinkley A, Motovilov, Katherine, Michael Brode, W et al.·Brain, behavior, and immunity·2025

This review examines intravenous immunoglobulin (IVIG), a treatment that works by providing immune-boosting antibodies, for several conditions including ME/CFS and long COVID. The researchers found that IVIG may help reduce symptoms in some patients, though results have been mixed. The treatment can have side effects and is very expensive, which limits how widely it can be used.

Immune System