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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 6,171 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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1198 studies

E0 — Consensus644E1 — Replicated320E2 — Moderate2,785E3 — Preliminary2,422

ME/CFS4,028Long COVID217Post-infectious189Overlapping1,051

Required for diagnosis415Not specified / unclear2,222Not required3,534

Post-Exertional Malaise1,067Cognitive Dysfunction1,737Pain1,621Unrefreshing Sleep800Orthostatic Intolerance479

Cytokines819Gene Expression568Metabolomics475Neuroimaging468Autoantibodies458

Infection-Triggered1,175Long COVID Overlap589Pediatric494Severe231

Strong Phenotyping439Sex-Stratified327Severe ME Included118

Systematic Review266Meta-Analysis60RCT300

Peer-reviewed6,114Preprint3Unclear54

1081–1100 of 1,198 studies

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 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 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 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 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 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 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 PreliminaryMechanismPEM not requiredCross-Sectional

Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome.

Cannon, J G, Angel, J B, Abad, L W et al.·Journal of clinical immunology·1998

Researchers compared how the bodies of women with ME/CFS and healthy women respond to exercise, focusing on immune cells called neutrophils and stress hormones. Both groups showed similar increases in neutrophils after 15 minutes of stepping exercise. However, in healthy women, the neutrophil response was linked to hormone levels (like cortisol and progesterone), while these connections were absent in women with ME/CFS—suggesting their hormonal regulation of immune cells may work differently.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Natural killer cells and natural killer cell activity in chronic fatigue syndrome.

Whiteside, T L, Friberg, D·The American journal of medicine·1998

This study examines natural killer (NK) cells—white blood cells that help fight infections and abnormal cells—in people with ME/CFS. The researchers found that many ME/CFS patients have lower-than-normal NK cell activity. The study explores why this happens and how it might be related to the disease, while also noting that findings have been difficult to confirm across different studies.

E3 PreliminaryMechanismPEM not requiredMechanistic

CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone.

Visser, J, Blauw, B, Hinloopen, B et al.·The Journal of infectious diseases·1998

This study looked at immune cells called CD4 T cells from ME/CFS patients and found they produced less of a protective immune protein called interferon-gamma compared to healthy people. Interestingly, these cells were also much more sensitive to dexamethasone, a steroid medication—it took 10-20 times less of the drug to suppress certain immune functions in ME/CFS patients than in controls. This suggests that the stress hormone system and immune system may be working abnormally together in ME/CFS.

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.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome.

Glaser, R, Kiecolt-Glaser, J K·The American journal of medicine·1998

This review examines whether ME/CFS might be triggered by viruses interacting with stress and the immune system. While doctors had noticed that people with ME/CFS often have signs of viral infection, previous research hadn't found a clear virus-to-ME/CFS connection. The authors explore how stress, dormant viruses like Epstein-Barr, and the body's immune response could work together to cause ME/CFS symptoms.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Decreased immunoreactive beta-endorphin in mononuclear leucocytes from patients with chronic fatigue syndrome.

Conti, F, Pittoni, V, Sacerdote, P et al.·Clinical and experimental rheumatology·1998

Researchers measured levels of beta-endorphin, a natural chemical in the body that helps reduce pain and promotes well-being, in immune cells from ME/CFS patients and healthy people. They found that ME/CFS patients had significantly lower levels of this chemical compared to healthy controls. The authors suggest this difference might help explain why ME/CFS causes fatigue and weakness.

E3 PreliminaryMechanismPEM not requiredMechanistic

The in vitro immunomodulatory effects of glyconutrients on peripheral blood mononuclear cells of patients with chronic fatigue syndrome.

See, D M, Cimoch, P, Chou, S et al.·Integrative physiological and behavioral science : the official journal of the Pavlovian Society·1998

This study tested whether a supplement containing eight specific sugars (called glyconutrients) could help fix immune system problems in ME/CFS patients. Researchers added the supplement to immune cells from ME/CFS patients and healthy controls in a laboratory dish and measured whether it improved immune function. The supplement appeared to increase the activity of several types of immune cells and reduce cell death in ME/CFS patients' immune cells.

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 PreliminaryCohortPEM not requiredCase-Control

Dysfunction of natural killer activity in a family with chronic fatigue syndrome.

Levine, P H, Whiteside, T L, Friberg, D et al.·Clinical immunology and immunopathology·1998

Researchers studied a family where 8 members had ME/CFS and found that their natural killer (NK) cells—immune cells that help fight infections and cancer—were not working as well as they should. Some unaffected family members also had lower NK activity, suggesting this might be an inherited trait. The findings raise the possibility that a genetic weakness in immune function could increase risk for both ME/CFS and cancer in this family.

E3 PreliminaryCommentaryPEM unclearEditorial

Silicone breast implants and autoimmune disease.

Brown, S L, Langone, J J, Brinton, L A·Journal of the American Medical Women's Association (1972)·1998

In 1992, the FDA paused approval of silicone breast implants due to safety concerns, particularly worries about autoimmune diseases like scleroderma. This editorial reviews studies conducted since then and finds that while large increases in connective tissue disease overall were ruled out, studies were too small to detect rare diseases. The authors note that new methodologies for studying conditions like fibromyalgia and chronic fatigue syndrome might help answer whether implants cause a specific syndrome.

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.

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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.