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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 6,206 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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1205 studies

E0 — Consensus655E1 — Replicated321E2 — Moderate2,807E3 — Preliminary2,423

ME/CFS4,041Long COVID224Post-infectious190Overlapping1,064

Required for diagnosis417Not specified / unclear2,252Not required3,537

Post-Exertional Malaise1,082Cognitive Dysfunction1,750Pain1,629Unrefreshing Sleep805Orthostatic Intolerance484

Cytokines821Gene Expression573Metabolomics478Neuroimaging472Autoantibodies460

Infection-Triggered1,182Long COVID Overlap604Pediatric496Severe232

Strong Phenotyping445Sex-Stratified330Severe ME Included119

Systematic Review272Meta-Analysis61RCT301

Peer-reviewed6,149Preprint3Unclear54

1081–1100 of 1,205 studies

E3 PreliminaryMechanismPEM unclearMechanistic

Chronic fatigue syndrome is not associated with expression of endogenous retroviral p15E.

Gelman, I H, Unger, E R, Mawle, A C et al.·Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology·2000

Researchers investigated whether a virus called endogenous retroviral p15E might be involved in causing ME/CFS. They tested blood samples from people with ME/CFS and compared them to healthy controls. The study found no evidence that this viral protein was present in higher amounts in ME/CFS patients, suggesting it is not responsible for the disease.

E3 PreliminaryReviewPEM unclearReview-Narrative

[Chronic fatigue syndrome].

Kuratsune, H·Ryoikibetsu shokogun shirizu·2000

This is a review article that summarizes what was known about chronic fatigue syndrome (ME/CFS) around the year 2000. Rather than conducting a new experiment, the author examined existing research to provide an overview of the condition. It helps explain what ME/CFS is and what scientists understood about it at that time.

E3 PreliminaryReviewPEM unclearReview-Narrative

The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system.

Elenkov, I J, Wilder, R L, Chrousos, G P et al.·Pharmacological reviews·2000

Your brain and immune system communicate constantly to keep your body healthy, and your nervous system plays a key role in this conversation. This review explains how nerve signals release chemicals called norepinephrine and epinephrine that can either calm down or activate your immune system depending on where in your body they act. Understanding this communication system may help explain why chronic conditions like fatigue syndromes involve both nervous system and immune system problems.

E3 PreliminaryMechanismPEM unclearCase-Control

Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion.

LaManca, J J, Sisto, S A, Zhou, X D et al.·Journal of clinical immunology·1999

Researchers tested whether people with ME/CFS have an unusual immune system response to hard exercise compared to healthy people who don't exercise regularly. They had 20 women with ME/CFS and 14 healthy women do an exhausting treadmill test, then checked their blood for immune cells and immune chemicals at several time points. While people with ME/CFS reported much worse fatigue 24 hours later, their immune systems actually responded to the exercise in the same way as the healthy controls.

Immune SystemPost-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

[Immunological aspects of pathophysiology of chronic fatigue syndrome].

Matsumoto, Y·Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology·1999

This study examined how the immune system functions differently in people with ME/CFS compared to healthy individuals. The researchers looked at various immune markers to understand what might be going wrong in the body during this illness. This type of research helps scientists figure out whether ME/CFS is caused by immune system problems.

E3 PreliminaryCohortPEM unclearCase-Control

[Autoimmune fatigue syndrome and fibromyalgia syndrome].

Itoh, Y, Igarashi, T, Tatsuma, N et al.·Nihon Ika Daigaku zasshi·1999

This study looked at two patients who were initially thought to have autoimmune fatigue syndrome (a condition where the immune system may attack the body and cause tiredness) but were later found to have fibromyalgia (widespread muscle pain and tender points). The researchers wondered if these two conditions might be related, so they checked how many tender points fibromyalgia patients had and looked at their immune markers. They found that patients with certain immune patterns had more tender points, suggesting autoimmunity might play a role in both conditions.

E3 PreliminaryCohortPEM not requiredCase-Control

Borna disease virus infection in two family clusters of patients with chronic fatigue syndrome.

Nakaya, T, Takahashi, H, Nakamur, Y et al.·Microbiology and immunology·1999

This study examined two families where multiple members had ME/CFS and looked for evidence of Borna disease virus (BDV) infection. Researchers found that family members diagnosed with ME/CFS had signs of BDV infection (antibodies and viral RNA), while most healthy family members did not. This suggests a possible link between this virus and ME/CFS, and raises the question of whether the virus might spread within families.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Fungal spores: hazardous to health?

Sorenson, W G·Environmental health perspectives·1999

This review discusses how fungal spores in the air can affect human health. Fungal spores are tiny particles that can enter the lungs when inhaled, and some contain harmful substances called mycotoxins. The article notes that breathing in fungal spores has been linked to various health problems, including chronic fatigue syndrome, along with lung disease and other serious conditions.

E3 PreliminaryMechanismPEM not requiredMechanistic

Stealth adaptation of an African green monkey simian cytomegalovirus.

Martin, W J·Experimental and molecular pathology·1999

Researchers found genetic material from a virus in a patient with chronic fatigue syndrome that resembles human cytomegalovirus (a common virus). Interestingly, the virus was missing genes that the immune system normally recognizes and attacks, which might allow it to hide from immune defenses. Genetic analysis showed this virus actually came from African green monkeys, not humans.

E3 PreliminaryCohortPEM not requiredCross-Sectional

Clinical features and IgG subclass distribution of anti-p80 coilin antibodies.

Onouchi, H, Muro, Y, Tomita, Y·Journal of autoimmunity·1999

Researchers tested blood samples from 365 Japanese patients and found 11 with unusual antibodies called anti-p80-coilin antibodies. All 11 were young women experiencing fatigue, joint pain, headaches, and other symptoms similar to ME/CFS. The study found that these antibodies come in different types, and one type (IgG2) might be a marker for autoimmune disease.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Immunity Impairment as a Result of Neurohormonal Disorders.

Artsimovich, Nelli G., Galushina, Tatyana S., Matvienko, Marina A. et al.·Russian journal of immunology : RJI : official journal of Russian Society of Immunology·1999

This study explores how the brain, hormones, and immune system are connected in ME/CFS. Researchers propose that immune cells communicate with the brain through special chemical messengers, and that problems in this communication system may contribute to ME/CFS symptoms. The study reviews evidence that people with ME/CFS have abnormal levels of certain immune markers and hormones.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome.

De Becker, P, De Meirleir, K, Joos, E et al.·Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme·1999

This study tested how the adrenal glands respond to a hormone signal in ME/CFS patients compared to healthy people. Researchers gave a hormone called ACTH to 22 ME/CFS patients and 14 healthy controls, then measured DHEA levels over an hour. While starting DHEA levels were normal, ME/CFS patients showed a weaker increase in DHEA after the hormone injection compared to healthy controls.

E3 PreliminaryMechanismPEM not requiredMechanistic

Acute phase responses and cytokine secretion in chronic fatigue syndrome.

Cannon, J G, Angel, J B, Ball, R W et al.·Journal of clinical immunology·1999

This study tested whether people with ME/CFS have abnormal levels of immune signaling molecules called cytokines, which could explain their symptoms. Researchers compared 10 ME/CFS patients with 11 healthy controls at rest and after 15 minutes of stepping exercise, measuring immune markers in their blood. They found that ME/CFS patients had higher baseline levels of certain inflammatory markers, but exercise responses were similar between groups.

E3 PreliminaryMechanismPEM not requiredCase-Control

Interferon-induced proteins are elevated in blood samples of patients with chemically or virally induced chronic fatigue syndrome.

Vojdani, A, Lapp, C W·Immunopharmacology and immunotoxicology·1999

This study found that certain immune proteins called 2-5A and PKR are elevated in the blood of ME/CFS patients, whether their illness was triggered by a viral infection or chemical exposure. The researchers discovered that these two triggers activate these proteins through different biological pathways—viruses primarily use an immune signaling molecule called interferon-beta, while chemicals activate them mainly through heat shock proteins.

BiomarkersImmune System

E3 PreliminaryMechanismPEM unclearMechanistic

Chronic fatigue syndrome and/or fibromyalgia as a variation of antiphospholipid antibody syndrome: an explanatory model and approach to laboratory diagnosis.

Berg, D, Berg, L H, Couvaras, J et al.·Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis·1999

This study proposes that ME/CFS and fibromyalgia may be caused by low-level blood clotting activation triggered by certain antibodies in the immune system. Researchers used five specific blood tests to detect signs of abnormal clotting in patients with these conditions. If confirmed, this finding could help doctors diagnose these diseases and monitor treatment with blood-thinning medications.

E3 PreliminaryCommentaryPEM not requiredEditorial

Chronic fatigue syndrome: new insights and old ignorance.

Evengård, B, Schacterle, R S, Komaroff, A L·Journal of internal medicine·1999

ME/CFS is a complex condition that affects thinking, sleep quality, and causes physical symptoms like sore throats, muscle pain, and exhaustion after activity. While many patients report that their illness began with an infection, scientists still don't fully understand how infections connect to ME/CFS. Research shows the immune system is overactive and certain brain systems aren't working normally, suggesting ME/CFS involves multiple body systems.

Immune SystemPost-Exertional Malaise

E3 PreliminaryReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome: an update.

Komaroff, A L, Buchwald, D S·Annual review of medicine·1998

This review examines chronic fatigue syndrome (ME/CFS), a serious condition where people experience extreme tiredness and other symptoms that last at least six months. The authors explain that ME/CFS is not simply depression or a mental health problem, but rather involves real physical changes in the body including immune system activation and issues with hormone-regulating glands. Understanding these biological features helps validate that ME/CFS is a genuine medical illness deserving proper research and treatment.

E3 PreliminaryReviewPEM unclearReview-Narrative

Pathogenesis of chronic fatigue syndrome and fibromyalgia.

Klimas, N·Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society·1998

This 1998 review article explores how ME/CFS and fibromyalgia may develop, focusing on potential biological mechanisms in the body. The researchers, led by Dr. Nancy Klimas, examined connections between growth hormone, immune system dysfunction, and the symptoms patients experience. Understanding these underlying causes is an important step toward better treatments.

E3 PreliminaryCommentaryPEM unclearEditorial

Future directions in exercise and immunology: regulation and integration.

Mackinnon, L T·International journal of sports medicine·1998

This editorial discusses how exercise affects the immune system and raises important questions for future research. It explores whether athletes' bodies are actually fighting infections less effectively, whether reducing certain immune responses might sometimes be helpful, and how exercise training might help people with conditions like chronic fatigue syndrome improve their immune function.

E3 PreliminaryMechanismPEM not requiredMechanistic

Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome.

Ogawa, M, Nishiura, T, Yoshimura, M et al.·European journal of clinical investigation·1998

This study looked at how a common amino acid called L-arginine affects immune cells called natural killer cells in ME/CFS patients compared to healthy people. The researchers found that L-arginine boosted natural killer cell activity in healthy volunteers, but this boost didn't happen in ME/CFS patients. The difference appears to be related to how the body produces nitric oxide, a chemical messenger involved in immune function.

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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.