Evidence browser

NeuroinflammationImmune System

The microbiota-gut-brain axis in myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review of an emerging field.

El-Sehrawy, Amr Ali Mohamed Abdelgawwad, Ayoub, Ibtihal Ibrahim, Uthirapathy, Subasini et al.·European journal of translational myology·2025

This review examines how bacteria in your gut may be connected to ME/CFS symptoms like fatigue and brain fog. Researchers looked at studies from 1995 to 2025 about how gut bacteria communicate with the brain and immune system. The review suggests that fixing imbalances in gut bacteria might help treat ME/CFS, though more research is needed to confirm this.

E0 ConsensusReviewPEM not requiredReview-Narrative

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 SystemCognitive ImpairmentPost-Exertional Malaise

Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Ivanovska, Mariya, Homadi, Maysam Salim, Angelova, Gergana et al.·Biomedicines·2025

This review compared Long-COVID (illness after COVID-19) and ME/CFS (chronic fatigue syndrome), which share similar symptoms like extreme tiredness, difficulty thinking clearly, and problems with the nervous system. While both conditions likely involve immune system problems, viral persistence, and blood vessel issues, they appear to have some differences in how they develop. Currently, there is no cure for either condition, though lifestyle management and rehabilitation help some people.

E0 ConsensusReviewPEM requiredSystematic-Review

Applicability and adaptation of cognitive behavior therapy for long COVID neuropsychiatric symptoms: a review with insights from ME/CFS.

Takamatsu, Naoki, Kuga, Hironori·BMC infectious diseases·2025

This review examined whether cognitive behavior therapy (CBT)—a talking therapy that helps address thought patterns and behaviors—might help patients with long COVID who experience brain fog, fatigue, and mood problems. The authors compared long COVID to ME/CFS, noting they share many features, and found that while CBT may help some patients feel less tired and think more clearly, it works best when tailored to each person's energy limits and combined with other treatments. Importantly, the authors stress that suggesting CBT does not mean these illnesses are 'all in your head'—they have real physical causes.

NeuroinflammationImmune SystemPost-Exertional Malaise

E0 ConsensusReviewPEM unclearSystematic-Review

Epigenetic changes in patients with post-acute COVID-19 symptoms (PACS) and long-COVID: A systematic review.

Shekhar Patil, Madhura, Richter, Emma, Fanning, Lara et al.·Expert reviews in molecular medicine·2024

This review examined research on how long-COVID changes the way genes are turned on and off in the body—a process called epigenetics. Researchers found that these changes may affect the immune system, nervous system, and how cells use energy. While the findings are interesting and promise better treatments in the future, current research is still limited in size and quality.

NeuroinflammationImmune System

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders.

Cohen, Jessica, Mathew, Annette, Dourvetakis, Kirk D et al.·Cells·2024

This review examines how inflammation in the brain and nervous system contributes to several chronic diseases, including ME/CFS and Gulf War Illness. The authors discuss how immune cells and inflammatory molecules can damage the brain and cause persistent symptoms. They highlight promising new laboratory techniques using human stem cells to create brain cells for testing potential treatments.

E0 ConsensusReviewPEM not requiredReview-Narrative

Research progress on pathogenesis of chronic fatigue syndrome and treatment of traditional Chinese and Western medicine.

Liu, Tingting, Sun, Weibo, Guo, Shuhao et al.·Autonomic neuroscience : basic & clinical·2024

This review examines what scientists currently understand about ME/CFS—a debilitating condition characterized by extreme fatigue that doesn't improve with rest, along with other symptoms like muscle pain, sore throat, and sleep problems. The authors looked at research on possible causes (like viral infections, stress, and immune system problems) and discussed how both conventional medicine and Traditional Chinese Medicine approaches might help treat the condition.

BiomarkersImmune SystemCognitive ImpairmentPost-Exertional Malaise

Chronic Fatigue Syndrome: Diagnosis, Treatment, and Future Direction.

Graves, B Sue, Patel, Mitsu, Newgent, Hailey et al.·Cureus·2024

ME/CFS is a serious illness that causes extreme tiredness that doesn't improve with rest and often gets worse with activity. People with ME/CFS also struggle with brain fog, pain, sleep problems, and immune system issues. Right now, doctors don't have a simple blood test or scan to diagnose ME/CFS, which makes it hard to identify and treat the condition properly.

E0 ConsensusReviewPEM unclearSystematic-Review

The impact of gut microbiome and diet on post-acute sequelae of SARS-CoV-2 infection.

Reyes, Zabrina, Stovall, Mary Catherine, Punyamurthula, Sanjana et al.·Journal of the neurological sciences·2024

This study looked at how gut bacteria and diet might affect people who develop Long COVID (symptoms that continue months after a COVID-19 infection). Researchers reviewed existing studies to see if changes in gut bacteria linked to worse COVID illness could be improved by eating foods rich in fiber and antioxidants, like those in the Mediterranean Diet. The idea is that a healthier gut might help prevent or reduce Long COVID symptoms.

Gut MicrobiomeImmune System

Energy MetabolismImmune System

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease.

Arron, Hayley E, Marsh, Benjamin D, Kell, Douglas B et al.·Frontiers in immunology·2024

This review examines what we know about ME/CFS by looking at how the disease develops from a combination of genetic factors, infections, and immune problems. The researchers found that ME/CFS appears to result from multiple body systems going wrong at the same time—including the immune system, inflammation, digestive health, and energy production. The study argues that doctors and scientists need to stop looking at ME/CFS as a single problem and instead understand it as a complex condition involving many interconnected issues.

E0 ConsensusReviewPEM unclearSystematic-Review

Identifying microRNAs Possibly Implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Review.

Tsamou, Maria, Kremers, Fabiënne A C, Samaritakis, Keano A et al.·International journal of molecular sciences·2024

This review examined tiny molecules called microRNAs that may play a role in ME/CFS and fibromyalgia. Researchers looked at existing studies to identify which microRNAs appear to be abnormal in these conditions and what role they might play in causing symptoms. They found that certain microRNAs may be involved in immune system problems, energy production difficulties, and increased pain sensitivity—processes that could help explain why people with these diseases experience fatigue, pain, and other symptoms.

BiomarkersImmune System

Autoimmunity's enigmatic role: exploring the connection with myalgic encephalomyelitis/chronic fatigue syndrome.

Batham, Jacob, Dwyer, Jessica, Eaton-Fitch, Natalie et al.·BMC immunology·2024

Researchers reviewed 10 studies to understand whether ME/CFS is caused by autoimmunity—a condition where the immune system attacks the body's own cells. While some signs of autoimmune activity were found in ME/CFS patients, the evidence is mixed and not strong enough to confirm that autoimmunity is the main cause. The authors conclude that ME/CFS is more complex than a straightforward autoimmune disease.

Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment.

Dooley, Ming, Vukelic, April, Jim, Lysander·Annals of medicine and surgery (2012)·2024

This review looked at studies about treatments for conditions involving long-term inflammation and fatigue, including ME/CFS. The researchers found that most published studies focused on a treatment approach called the Shoemaker Protocol, which was reported to work better than other treatments tested. However, this review only examined existing published articles rather than conducting new research, so the strength of the evidence depends heavily on the quality of those original studies.

E0 ConsensusReviewPEM not requiredSystematic-Review

Ear abnormalities in chronic fatigue syndrome (CFS), fibromyalgia (FM), Coronavirus-19 infectious disease (COVID) and long-COVID syndrome (PCS), sick-building syndrome (SBS), post-orthostatic tachycardia syndrome (PoTS), and autoimmune/inflammatory syndrome induced by adjuvants (ASIA): A systematic review.

Skare, Thelma L, de Carvalho, Jozélio Freire, de Medeiros, Italo Roberto Torres et al.·Autoimmunity reviews·2024

This review examined hearing and balance problems (including hearing loss, tinnitus, dizziness, and vertigo) reported across multiple conditions including ME/CFS, fibromyalgia, and long COVID. Researchers searched medical literature from 1990 to 2024 and found that while hearing problems are common, balance problems are less frequently reported. The study suggests these symptoms may stem from immune system dysfunction affecting the inner ear.

NeuroinflammationImmune System

Microglia and Sleep Disorders.

Picard, Katherine, Dolhan, Kira, Watters, Jyoti J et al.·Advances in neurobiology·2024

This review examines how microglia—immune cells in the brain and spinal cord—affect sleep and sleep disorders. The authors discuss how sleep problems and lack of sleep can harm brain health and potentially lead to diseases like Alzheimer's and Parkinson's. They specifically look at how microglia may be involved in ME/CFS and other sleep disorders, and what happens to these immune cells when people don't get enough sleep.

Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives.

Seton, Katharine A, Espejo-Oltra, José A, Giménez-Orenga, Karen et al.·Journal of clinical medicine·2024

This review examined research studies testing various treatments for ME/CFS, including medications and supplements that target different aspects of the illness like immune function, metabolism, and gut health. The authors found that current treatments mainly manage symptoms rather than address the root causes, with very few patients recovering fully. They emphasize that better-designed clinical trials are urgently needed to find treatments that actually work and can be used in real-world medical practice.

Translating insights into therapies for Long Covid.

Antar, Annukka A R, Cox, Andrea L·Science translational medicine·2024

Long Covid causes a variety of symptoms—like exhaustion, weakness, and brain fog—that last long after a COVID-19 infection ends. This review examines what scientists currently understand about what might cause Long Covid and looks at early laboratory studies and clinical trials testing potential treatments. The authors emphasize that more large-scale research is needed to understand why different people experience different symptoms and to develop effective therapies.

Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses.

Apostolou, Eirini, Rosén, Anders·Journal of internal medicine·2024

This review examines how viruses, particularly Epstein-Barr virus, may cause lasting changes to how our cells work in ME/CFS patients. The authors found that in about 70% of ME/CFS cases, the illness begins after a viral infection, and viruses can hide in the body while triggering long-term problems with energy, thinking, and immune function. Understanding these viral-triggered changes could help explain why different patients experience ME/CFS differently and may lead to better treatments.

The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives.

Stallmach, Andreas, Quickert, Stefanie, Puta, Christian et al.·Frontiers in immunology·2024

This review examines whether changes in gut bacteria might play a role in ME/CFS, particularly in cases that develop after infections like COVID-19. The authors found that many ME/CFS patients do show differences in their gut bacteria compared to healthy people, and these changes might trigger immune and inflammatory problems. However, the review concludes that current research hasn't proven that gut bacteria changes actually cause ME/CFS—only that they often occur together.

E0 ConsensusReviewPEM unclearMeta-Analysis

Meta-analysis of natural killer cell cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome.

Baraniuk, James N, Eaton-Fitch, Natalie, Marshall-Gradisnik, Sonya·Frontiers in immunology·2024

Researchers combined results from 28 previous studies to confirm that people with ME/CFS have natural killer (NK) cells—a type of immune cell that fights infections and abnormal cells—that work at about half the strength of healthy people's NK cells. This is one of the most reliable biological differences found in ME/CFS. The analysis confirms this is a real, consistent problem in the condition.