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ME/CFS Atlas — A public knowledge atlas for ME/CFS

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ME/CFS Atlas is an evidence reference platform, not a medical provider. Content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

Evidence browser

Search and filter 6,119 studies by evidence level, diagnostic criteria, PEM status, and research domain. Each entry links to the original source.

Studies sorted by evidence level, then year. Browse by topic instead →

Evidence level (E0–E3) reflects study type and replication, not methodological quality. A weak systematic review still sits at E0. How evidence levels work →

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1185 studies

E0 — Consensus628E1 — Replicated319E2 — Moderate2,756E3 — Preliminary2,416

ME/CFS4,009Long COVID207Post-infectious188Overlapping1,031

Required for diagnosis409Not specified / unclear2,190Not required3,520

Post-Exertional Malaise1,039Cognitive Dysfunction1,711Pain1,606Unrefreshing Sleep786Orthostatic Intolerance470

Cytokines812Gene Expression564Metabolomics469Neuroimaging464Autoantibodies454

Infection-Triggered1,157Long COVID Overlap563Pediatric494Severe227

Strong Phenotyping427Sex-Stratified325Severe ME Included115

Systematic Review256Meta-Analysis59RCT299

Peer-reviewed6,062Preprint3Unclear54

101–120 of 1,185 studies

E0 ConsensusReviewPEM not requiredReview-Narrative

Natural killer cells in patients with severe chronic fatigue syndrome.

Brenu, E W, Hardcastle, S L, Atkinson, G M et al.·Auto- immunity highlights·2013

This review examined how natural killer (NK) cells—a type of white blood cell that fights infections and abnormal cells—work differently in ME/CFS patients. The researchers found that people with ME/CFS often have unusual numbers of NK cells or reduced ability to fight infections, which may help explain why patients suffer from persistent symptoms and recurrent infections. Understanding these immune cell problems could eventually lead to better treatments.

E0 ConsensusReviewPEM not requiredReview-Narrative

Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms?

Kim, S E, Chang, L·Neurogastroenterology and motility·2012

Many patients with ME/CFS experience overlapping conditions like irritable bowel syndrome, fibromyalgia, and jaw pain. This review looked at what ME/CFS and similar conditions might have in common. The researchers found that these disorders likely share several underlying problems: how the body processes pain, changes in brain activity, possible past infections, immune system problems, and genetic factors that make some people more vulnerable.

E0 ConsensusReviewPEM unclearReview-Narrative

Biomarkers for chronic fatigue.

Klimas, Nancy G, Broderick, Gordon, Fletcher, Mary Ann·Brain, behavior, and immunity·2012

This review examines blood tests and biological markers that might help diagnose ME/CFS, since current diagnosis relies only on symptoms. The researchers found that multiple body systems—including the immune system, stress hormones, and nervous system—appear to be disrupted in ME/CFS patients. However, no single test yet reliably identifies the condition, suggesting ME/CFS may involve complex changes across several systems rather than one simple cause.

E0 ConsensusReviewPEM not requiredMeta-Analysis

Meta analysis of Chronic Fatigue Syndrome through integration of clinical, gene expression, SNP and proteomic data.

Pihur, Vasyl, Datta, Somnath, Datta, Susmita·Bioinformation·2011

Researchers combined multiple types of biological data from ME/CFS patients and healthy controls to identify genes that may contribute to ME/CFS and its severity. They found 11 genes of potential importance, with one gene called WASF3 standing out as possibly influencing fatigue through a specific cellular pathway in the brain.

Immune SystemNeuroinflammation

E0 ConsensusReviewPEM unclearReview-Narrative

An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.

Maes, Michael·Progress in neuro-psychopharmacology & biological psychiatry·2011

Depression and ME/CFS often occur together, and this study suggests they share common biological root causes involving inflammation and oxidative stress (damage to cells). While depression and ME/CFS look different clinically, they appear to involve similar underlying problems with the immune system, energy production, and antioxidant defenses. The authors argue these should be considered connected disorders rather than two separate conditions that happen to co-occur.

Immune SystemNeuroinflammation

E0 ConsensusReviewPEM not requiredReview-Narrative

Neuroaetiology of chronic fatigue syndrome: an overview.

Sanders, Patricia, Korf, Jakob·The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry·2008

This review examines several competing theories about what causes ME/CFS. The authors found that while viral infections, brain hormone imbalances, immune problems, and psychological factors are all proposed as causes, none has been definitively proven. The authors suggest that ME/CFS may not be one single disease, but rather several different conditions that produce similar symptoms, which could explain why treatments like cognitive behavioral therapy work for some patients but not others.

E0 ConsensusReviewPEM not requiredReview-Narrative

[Chronic fatigue syndrome: biochemical examination of blood].

Hakariya, Yukiko, Kuratsune, Hirohiko·Nihon rinsho. Japanese journal of clinical medicine·2007

This review examined blood test abnormalities in ME/CFS patients. While standard blood tests often appear normal in CFS patients despite their many symptoms, specialized blood tests have found problems in the systems that control stress, hormones, and immune function. The authors suggest that ME/CFS may result from brain dysfunction caused by immune chemicals called cytokines or antibodies that attack the body's own cells.

E0 ConsensusReviewPEM not requiredReview-Narrative

[Viral infections in chronic fatigue syndrome].

Sairenji, Takeshi, Nagata, Keiko·Nihon rinsho. Japanese journal of clinical medicine·2007

This review looked at research on whether viruses and other infections might trigger ME/CFS. Most people with ME/CFS report having a flu-like illness before their symptoms started, which led researchers to investigate if infections could cause long-term immune system problems. The authors summarized what scientists have learned about different viruses, bacteria-like organisms, and other microbes that might be involved in ME/CFS development.

E0 ConsensusReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology.

Cho, Hyong Jin, Skowera, Anna, Cleare, Anthony et al.·Current opinion in psychiatry·2006

This review examines what ME/CFS is and how it works in the body. The research shows that ME/CFS is a real condition separate from depression or anxiety, though the official way doctors diagnose it may need updating. Scientists have found signs that the nervous system, immune system, and genetics all play a role, but they still don't fully understand how these pieces fit together.

E0 ConsensusReviewPEM not requiredSystematic-Review

A systematic review and critical evaluation of the immunology of chronic fatigue syndrome.

Lyall, Marc, Peakman, Mark, Wessely, Simon·Journal of psychosomatic research·2003

Researchers reviewed all the studies looking at immune system problems in ME/CFS patients to see what patterns emerged. They found that results were mixed and often contradictory—some studies showed low natural killer cells, while others didn't, especially when looking at higher-quality research. The review suggests that how studies are designed and conducted can affect whether certain immune changes are found.

E0 ConsensusReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome: reviewing the research findings.

Johnson, S K, DeLuca, J, Natelson, B H·Annals of behavioral medicine : a publication of the Society of Behavioral Medicine·1999

This 1999 review summarizes what researchers had learned about ME/CFS up to that point, covering theories about its causes, how common it is, and what treatments were being studied. The authors found that ME/CFS appears to involve multiple factors—psychiatric, immune, neurological, and hormonal—rather than a single cause, and that patients may represent different subgroups. However, as a review of existing literature rather than a new study, it reports on what other researchers had observed rather than providing definitive answers about the illness itself.

E0 ConsensusReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome: an immunological perspective.

Vollmer-Conna, U, Lloyd, A, Hickie, I et al.·The Australian and New Zealand journal of psychiatry·1998

This review examines whether immune system problems might cause ME/CFS symptoms, particularly in the brain. The researchers found that while immune chemicals called cytokines are likely involved in ME/CFS, the results from studies measuring these chemicals in the blood have been mixed and unclear. They suggest that abnormal cytokine activity happening directly inside the brain—rather than in the bloodstream—may be more important for explaining the neurological symptoms patients experience.

E0 ConsensusReviewPEM not requiredReview-Narrative

Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms.

Clauw, D J, Chrousos, G P·Neuroimmunomodulation·1997

This review examines fibromyalgia and chronic fatigue syndrome, two conditions with overlapping symptoms of pain and exhaustion that have been described throughout medical history under different names. The authors propose that both conditions stem from problems in the central nervous system—the brain and spinal cord—particularly in areas that control hormone levels, pain sensing, and automatic body functions. They suggest that immune system changes seen in these conditions are side effects rather than root causes.

Immune SystemAutonomic Nervous System

E0 ConsensusReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome. 1: Etiology and pathogenesis.

Farrar, D J, Locke, S E, Kantrowitz, F G·Behavioral medicine (Washington, D.C.)·1995

ME/CFS is a serious illness that causes extreme tiredness and many other symptoms, but doctors don't yet fully understand what causes it or how to treat it best. This review looks at research about what might be happening in the body—including problems with the immune system and stress hormone regulation—but notes that no single explanation has been proven. Right now, treatment approaches are based on guesses rather than solid evidence, and we need better ways to identify which patients have which type of ME/CFS.

E0 ConsensusReviewPEM not requiredReview-Narrative

Clinical correlates of infection with human herpesvirus-6.

Krueger, G R, Klueppelberg, U, Hoffmann, A et al.·In vivo (Athens, Greece)·1994

This review examines connections between human herpesvirus-6 (HHV-6), a common virus most people catch as infants, and various illnesses including ME/CFS. The virus usually stays dormant in the body after infection, but in some people it may reactivate and be linked to several health conditions. The authors reviewed existing knowledge about which diseases show signs of active HHV-6 infection.

E0 ConsensusReviewPEM not requiredReview-Narrative

Pathogenic tracks in fatigue syndromes.

Moutschen, M, Triffaux, J M, Demonty, J et al.·Acta clinica Belgica·1994

This review examined research on ME/CFS and related fatigue conditions that develop after viral infections, looking at five main areas: infectious triggers, immune system problems, muscle function, hormonal imbalances, and psychiatric factors. The authors suggest that abnormalities in the body's stress-hormone system (HPA axis) may be a primary cause, leading to chronic immune activation and reactivation of dormant viruses like those in the herpes family, which then cause muscle weakness and fatigue symptoms.

E0 ConsensusReviewPEM not requiredReview-Narrative

Studies of herpesvirus infection in chronic fatigue syndrome.

Straus, S E·Ciba Foundation symposium·1993

This review examined whether common viruses in the herpesvirus family (like Epstein-Barr virus and human herpesvirus 6) cause ME/CFS. Researchers found that while some ME/CFS patients have higher levels of antibodies to these viruses and some cases may start after herpesvirus infection, these viruses are likely not the main cause of the illness for most people.

E0 ConsensusReviewPEM not requiredReview-Narrative

The pathophysiology of chronic fatigue syndrome: confirmations, contradictions, and conjectures.

Manu, P, Lane, T J, Matthews, D A·International journal of psychiatry in medicine·1992

This 1992 review examined 32 published studies on ME/CFS to identify what researchers had consistently found, disagreed about, or only reported once. The review confirmed that ME/CFS primarily affects middle-aged white women and is often accompanied by depression, but found conflicting evidence about whether infections cause the illness and whether immune treatments help.

E0 ConsensusReviewPEM not requiredReview-Narrative

Serologic and immunologic responses in chronic fatigue syndrome with emphasis on the Epstein-Barr virus.

Jones, J F·Reviews of infectious diseases·1991

This review examined whether ME/CFS is connected to Epstein-Barr virus (EBV), the virus that causes mono. Researchers found that people with ME/CFS had higher levels of antibodies to EBV compared to healthy people, but this doesn't prove the virus causes the disease. They also found that immune cells called natural killer cells—which help fight infections—work differently in ME/CFS patients, though the findings varied between studies.

E0 ConsensusReviewPEM not requiredReview-Narrative

Review of laboratory findings for patients with chronic fatigue syndrome.

Buchwald, D, Komaroff, A L·Reviews of infectious diseases·1991

This review examined blood test results from many ME/CFS patients and found several patterns in how their immune systems function differently. The most common findings included weaker natural killer cells (which normally help fight infections), unusual antibody levels, and signs of past Epstein-Barr virus infection. These patterns appeared across multiple studies, suggesting they may be important features of the condition.

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PEM Immune Neuro Metabolic Biomarkers Severe ME Long COVID Cognitive

Curated Collections

Thematic groupings by clinical question or research area.

Neuroinflammation Evidence

PET imaging and other studies providing evidence for brain inflammation in ME/CFS.

Metabolism & Mitochondria

Metabolomics and mitochondrial function studies revealing energy metabolism disruption.

Biomarkers

Studies identifying potential biological markers for ME/CFS diagnosis and stratification.

PEM-Specific Research

Studies specifically examining post-exertional malaise, the hallmark symptom of ME/CFS.