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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

1121–1140 of 1,198 studies

E3 PreliminaryCohortPEM not requiredCase-Control

Use of anti HHV-6 transfer factor for the treatment of two patients with chronic fatigue syndrome (CFS). Two case reports.

Ablashi, D V, Levine, P H, De Vinci, C et al.·Biotherapy (Dordrecht, Netherlands)·1996

This small study tested whether a special immune treatment called transfer factor, designed to target HHV-6 (a virus that may be active in some ME/CFS patients), could help. Two ME/CFS patients with active HHV-6 infection received this treatment. One patient improved significantly and returned to normal activities within weeks, but the other patient saw no improvement. The results suggest this treatment might help control HHV-6 in some patients, but more research is needed.

E3 PreliminaryCommentaryPEM not requiredEditorial

The use of transfer factors in chronic fatigue syndrome: prospects and problems.

Levine, P H·Biotherapy (Dordrecht, Netherlands)·1996

ME/CFS often starts with a viral infection and some people have ongoing herpes virus activity. This article discusses transfer factors—a type of immune therapy—that might help fight these viruses and improve symptoms. The authors explain why we need better-designed studies to test if this treatment actually works.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Use of exercise for treatment of chronic fatigue syndrome.

McCully, K K, Sisto, S A, Natelson, B H·Sports medicine (Auckland, N.Z.)·1996

This review looks at whether exercise can help people with ME/CFS feel better. While patients often report getting much sicker after even light activity, most studies find their muscles work normally on standard tests. The authors suggest exercise training might help, but caution that avoiding 'relapses' (crashes) is critical, and more research is needed to understand how exercise affects this illness.

Immune SystemPost-Exertional Malaise

E3 PreliminaryCohortPEM unclearCross-Sectional

Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome.

Nakaya, T, Takahashi, H, Nakamura, Y et al.·FEBS letters·1996

Researchers tested blood cells from 25 Japanese patients with chronic fatigue syndrome (ME/CFS) to see if a virus called Borna disease virus (BDV) was present. They found evidence of BDV in 3 patients' blood cells and antibodies (immune markers) against BDV in 6 patients, suggesting about 32% of their study group may have been exposed to or infected with this virus. This finding raised the possibility that BDV might be connected to ME/CFS in Japanese patients.

E3 PreliminaryReviewPEM unclearReview-Narrative

Neuroimmune mechanisms in health and disease: 2. Disease.

Anisman, H, Baines, M G, Berczi, I et al.·CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne·1996

When your body fights an infection, your immune system releases chemical messengers called cytokines that trigger fatigue, fever, loss of appetite, and inactivity—changes controlled partly by your brain and nervous system. This review explains how problems in the communication between your immune system and brain (particularly an area called the hypothalamus-pituitary-adrenal axis) may contribute to chronic conditions including ME/CFS, fibromyalgia, and autoimmune diseases. Understanding these connections could lead to new treatments using hormones and other brain-signaling molecules.

E3 PreliminaryCohortPEM not requiredCase-Control

Epstein-Barr virus-related primary cutaneous amyloidosis. Successful treatment with acyclovir and interferon-alpha.

Drago, F, Ranieri, E, Pastorino, A et al.·The British journal of dermatology·1996

This case report describes a woman with ME/CFS who developed unusual skin lesions (brownish patches and bumps) on her chest and back for 10 years. Doctors found that the Epstein-Barr virus (EBV)—the virus that causes mononucleosis—was active in her skin and other body areas, and abnormal protein deposits were building up in her skin. When she was treated with antiviral medication (acyclovir) and a type of immune-boosting therapy (interferon-alpha), both her skin lesions and other symptoms improved significantly.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Neurobiology of chronic fatigue syndrome.

Gonzalez, M B, Cousins, J C, Doraiswamy, P M·Progress in neuro-psychopharmacology & biological psychiatry·1996

This review article examines what happens in the brain and nervous system of people with ME/CFS. Researchers found that ME/CFS involves real biological changes in the brain—not just fatigue—including problems with mood, thinking, and hormone regulation. The study suggests that ME/CFS is a neurological condition with measurable differences in brain function, rather than purely psychological.

E3 PreliminaryReviewPEM unclearReview-Narrative

Neuroimmune and neuropsychiatric aspects of chronic fatigue syndrome.

Krupp, L B, Pollina, D·Advances in neuroimmunology·1996

This review examined how the immune system and nervous system may both contribute to ME/CFS symptoms. The authors looked at evidence that ME/CFS involves both brain-based changes and immune system dysfunction, which could explain why patients experience fatigue, cognitive problems, and mood changes.

E3 PreliminaryCohortPEM unclearCase-Control

A cluster of cases of chronic fatigue and chronic fatigue syndrome: clinical and immunologic studies.

Levine, P H, Dale, J K, Benson-Grigg, E et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1996

This study examined a group of people who developed chronic fatigue syndrome (ME/CFS), looking at their medical histories and immune system patterns to understand what might have caused their illness. Researchers compared patients with ME/CFS to control groups and measured various immune markers in their blood. The goal was to identify common features that might explain why these individuals became ill.

E3 PreliminaryReviewPEM unclearReview-Narrative

Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome.

Moldofsky, H·Advances in neuroimmunology·1995

This review examines how sleep problems, immune system dysfunction, and hormone imbalances may be connected in fibromyalgia and ME/CFS. The authors suggest that when the body's internal clock is disrupted, it can trigger a cascade of problems including poor sleep quality, pain, fatigue, and cognitive difficulties. They propose that studying these interconnected systems together—rather than separately—may help explain why these conditions are so disabling.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Are cytokines associated with neuropsychiatric syndromes in humans?

Hickie, I, Lloyd, A·International journal of immunopharmacology·1995

This paper suggests that immune molecules called cytokines—which your body produces during infections or inflammation—may affect your brain and behavior in ways that look like psychiatric symptoms such as depression, fatigue, loss of appetite, and difficulty thinking clearly. The authors review evidence from various illnesses where these immune-related behavioral changes happen together, including ME/CFS, and propose that cytokines may be the biological link between immune activation and these symptoms.

NeuroinflammationImmune System

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Chronic fatigue syndrome--a review of the literature].

Hamre, H J·Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke·1995

ME/CFS is a real medical condition that causes extreme tiredness, low-grade fevers, sore throats, and pain in joints and muscles, often starting after a flu-like illness. Exercise makes symptoms significantly worse. While doctors don't yet have a single blood test to diagnose it, research shows patients may have problems with brain blood flow, immune system issues, and mitochondrial (cellular energy) abnormalities.

Immune SystemPost-Exertional Malaise

E3 PreliminaryMechanismPEM not requiredCross-Sectional

The disease associations of the antibody response against the Epstein-Barr virus transactivator protein ZEBRA can be separated into different epitopes.

Tedeschi, R, Foong, Y T, Cheng, H M et al.·The Journal of general virology·1995

This study looked at antibody patterns against a specific EBV protein called ZEBRA, which becomes active when the virus 'wakes up' from dormancy. Researchers found that different parts of this protein trigger antibodies in different diseases—some patterns were more common in people with nasopharyngeal cancer, others in people with infectious mononucleosis, and some in people with chronic fatigue syndrome. This suggests that the type of EBV reactivation may differ depending on the illness someone has.

E3 PreliminaryCohortPEM not requiredCase-Control

Chronic active Epstein-Barr virus disease in a case of persistent polyclonal B-cell lymphocytosis.

Mitterer, M, Pescosta, N, Fend, F et al.·British journal of haematology·1995

This report describes one patient who had an unusual blood disorder involving too many B cells (immune cells) along with symptoms resembling chronic fatigue syndrome, including persistent tiredness and recurring skin rashes. Testing showed the patient had a chronic active Epstein-Barr virus (EBV) infection with the virus actively replicating in their blood cells. The researchers suggest that persistent EBV replication may play a role in developing this lymphoproliferative disorder.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Human herpesvirus-7 (HHV-7): current status.

Ablashi, D V, Berneman, Z N, Kramarsky, B et al.·Clinical and diagnostic virology·1995

This review article summarizes what scientists knew about human herpesvirus-7 (HHV-7) as of 1995, a newly discovered virus related to other common herpesviruses. HHV-7 was found in a chronic fatigue syndrome patient, along with healthy people, and is very common in the population (affecting over 85% of Americans). The virus has been linked to a few childhood rash illnesses and possibly some cases with liver involvement, but scientists had limited information about whether it causes ME/CFS.

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Biological and molecular characteristics of human herpesvirus 7: in vitro growth optimization and development of a syncytia inhibition test.

Secchiero, P, Berneman, Z N, Gallo, R C et al.·Virology·1994

Researchers studied human herpesvirus 7 (HHV-7), a common virus that infects most people, by growing it in the laboratory using immune cells from both a ME/CFS patient and a healthy person. They developed better methods to produce large amounts of the virus and created a test to detect antibodies (immune proteins) against HHV-7 in blood samples. They found that most people tested had antibodies to this virus, showing it spreads widely in the population.

E3 PreliminaryMechanismPEM not requiredMechanistic

Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome.

Suhadolnik, R J, Reichenbach, N L, Hitzges, P et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study found that people with ME/CFS have overactive immune signaling molecules called the 2-5A pathway in their blood cells, which normally fight viral infections. When patients received an experimental treatment, this overactive pathway calmed down and they improved clinically, and the researchers also found signs of a herpesvirus in almost all CFS patients tested.

E3 PreliminaryMechanismPEM unclearCross-Sectional

Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.

Peterson, P K, Sirr, S A, Grammith, F C et al.·Clinical and diagnostic laboratory immunology·1994

Researchers tested whether light exercise (30 minutes of slow walking) would trigger abnormal immune and brain blood flow responses in ME/CFS patients compared to healthy people. They found that ME/CFS patients had higher levels of a specific immune protein (TGF-beta) both at rest and after exercise, and also showed changes in brain blood flow. These changes appeared larger in ME/CFS patients than in healthy controls, though the difference wasn't statistically significant.

Immune SystemPost-Exertional Malaise

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Chronic fatigue syndrome--a defined unity?].

Rasmussen, A K, Andersen, V, Nielsen, H et al.·Ugeskrift for laeger·1994

This 1994 review examined what scientists knew about ME/CFS at that time, looking at whether a persistent virus or immune system problem caused the condition. The authors found that existing research did not consistently support either explanation, and that different studies often contradicted each other. They concluded that more careful research was needed to understand what actually causes ME/CFS and how to tell it apart from other illnesses.

Immune SystemPost-Exertional Malaise

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Human herpesvirus 6. General overview].

Tîrdei, G, Ruţă, S M, Popescu, A E·Revue roumaine de virologie (Bucharest, Romania : 1990)·1994

Human herpesvirus 6 (HHV6) is a common virus that infects most people before age three, usually causing no symptoms or only mild illness. Researchers have good understanding of how the virus works and spreads, but it remains unclear whether HHV6 plays a role in chronic fatigue syndrome and some other long-term illnesses. This review summarizes what we know and don't know about this virus.

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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.