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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 6,170 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 — Moderate2,784E3 — Preliminary2,422

ME/CFS4,027Long COVID217Post-infectious189Overlapping1,051

Required for diagnosis415Not specified / unclear2,221Not required3,534

Post-Exertional Malaise1,066Cognitive Dysfunction1,736Pain1,620Unrefreshing Sleep800Orthostatic Intolerance478

Cytokines819Gene Expression568Metabolomics475Neuroimaging468Autoantibodies458

Infection-Triggered1,175Long COVID Overlap589Pediatric494Severe231

Strong Phenotyping439Sex-Stratified327Severe ME Included118

Systematic Review266Meta-Analysis60RCT300

Peer-reviewed6,113Preprint3Unclear54

481–500 of 1,198 studies

E2 ModerateCohortPEM not requiredCross-Sectional

Impaired natural immunity, cognitive dysfunction, and physical symptoms in patients with chronic fatigue syndrome: preliminary evidence for a subgroup?

Siegel, Scott D, Antoni, Michael H, Fletcher, Mary Ann et al.·Journal of psychosomatic research·2006

This study looked at whether a specific immune system measure called natural killer cell activity (NKCA) could help identify different subgroups of ME/CFS patients. Researchers compared 41 women with ME/CFS who had low NKCA levels to those with normal levels, measuring their cognitive ability and symptoms. They found that patients with low NKCA reported worse cognitive problems, more daytime dysfunction, and performed worse on thinking tests compared to those with normal NKCA levels.

E2 ModerateCohortPEM not requiredCross-Sectional

Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS.

Maes, Michael, Mihaylova, Ivana, De Ruyter, Marcel·Journal of affective disorders·2006

This study found that people with ME/CFS have lower levels of zinc in their blood compared to healthy people. The lower the zinc level, the worse some symptoms were, especially feelings of infection. Zinc helps protect the body from harmful molecules called free radicals, so low zinc may be one reason why ME/CFS involves increased stress and damage in the body.

E2 ModerateCohortPEM not requiredCross-Sectional

Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome.

Chapenko, S, Krumina, A, Kozireva, S et al.·Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology·2006

This study looked at whether two common viruses (HHV-6 and HHV-7) that usually stay dormant in the body might be reactivating in people with ME/CFS. Researchers found that people with ME/CFS were more likely to have both viruses active at the same time, and when both were active, their immune cells showed signs of stress. This suggests these viruses might play a role in ME/CFS, though the study cannot prove they cause the disease.

E2 ModerateCohortPEM not requiredCross-Sectional

[Prevalence of atopy in chronic fatigue syndrome].

Ferré Ybarz, L, Cardona Dahl, V, Cadahía García, A et al.·Allergologia et immunopathologia·2005

Researchers compared allergies and allergic sensitivity in 25 people with ME/CFS to 20 healthy controls. While patients with ME/CFS reported slightly more respiratory symptoms and drug allergies, the study found no significant difference in overall allergic sensitization between the two groups. This suggests that allergies may not be a core feature of ME/CFS, though some patients do experience them.

E2 ModerateCohortPEM not requiredCross-Sectional

Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS.

Maes, Michael, Mihaylova, Ivana, De Ruyter, Marcel·Neuro endocrinology letters·2005

This study compared hormone levels in people with ME/CFS to healthy controls. Researchers found that ME/CFS patients had significantly lower levels of DHEAS (a hormone made by the adrenal glands), but normal levels of another hormone called IGF1. The low DHEAS was closely linked to markers of immune system activation and inflammation, suggesting this hormone imbalance may contribute to ME/CFS symptoms.

E2 ModerateCohortPEM not requiredObservational

Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome.

Vernon, Suzanne D, Reeves, William C·Journal of autoimmune diseases·2005

Researchers tested blood samples from people with ME/CFS and healthy controls to look for autoantibodies—proteins the immune system makes that can attack the body's own cells. They found that some people with ME/CFS had higher levels of antibodies against two specific targets: a brain protein called MAP2 and a component of DNA. However, most common autoantibodies were not elevated in ME/CFS patients.

BiomarkersImmune System

E2 ModerateCohortPEM not requiredCross-Sectional

Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome.

Gaab, Jens, Rohleder, Nicolas, Heitz, Vera et al.·Psychoneuroendocrinology·2005

This study tested how ME/CFS patients' immune systems respond to stress compared to healthy people. Researchers gave both groups a stressful public speaking task, then exposed their blood samples to a bacterial substance to measure immune response. Unlike healthy controls whose immune response increased after stress, ME/CFS patients showed a decreased immune response, suggesting their bodies may not mobilize infection-fighting chemicals normally during stress.

E2 ModerateCohortPEM not requiredCross-Sectional

Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression.

Robertson, M J, Schacterle, R S, Mackin, G A et al.·Clinical and experimental immunology·2005

This study looked at immune cells in the blood of people with ME/CFS and compared them to people with depression, multiple sclerosis, and healthy individuals. While the total numbers of major immune cell types were similar across groups, researchers found differences in specific subtypes of these cells, particularly in natural killer cells. This suggests that ME/CFS may involve changes in how the immune system is organized, even if total cell counts appear normal.

E2 ModerateCohortPEM not requiredCross-Sectional

Chronic fatigue syndrome: exercise performance related to immune dysfunction.

Nijs, Jo, Meeus, Mira, McGregor, Neil R et al.·Medicine and science in sports and exercise·2005

This study looked at whether problems with the immune system might explain why people with ME/CFS feel exhausted after exercise and cannot exercise as much as healthy people. Researchers tested 16 ME/CFS patients' immune cells and had them exercise on a stationary bike while measuring their oxygen use and heart rate. They found that two specific immune markers—elastase and protein kinase R—were linked to reduced exercise capacity, suggesting immune dysfunction may play a role in abnormal exercise responses.

E2 ModerateCohortPEM not requiredCross-Sectional

Exercise capacity and immune function in male and female patients with chronic fatigue syndrome (CFS).

Snell, Christopher R, Vanness, J Mark, Strayer, David R et al.·In vivo (Athens, Greece)·2005

This study looked at whether a specific immune system problem affects how much exercise people with ME/CFS can do. Researchers tested 106 ME/CFS patients (35 men and 71 women) on exercise machines and found that patients with abnormal immune activity had noticeably lower exercise capacity than those with normal immune function. The difference was about the same for both men and women.

E2 ModerateCohortPEM not requiredCase-Control

Association of chronic fatigue syndrome with human leucocyte antigen class II alleles.

Smith, J, Fritz, E L, Kerr, J R et al.·Journal of clinical pathology·2005

This study looked at whether certain genetic markers related to the immune system (called HLA types) are more common in people with ME/CFS than in healthy people. Researchers compared the genetic profiles of 49 ME/CFS patients with 102 healthy controls from the same region of England. They found that one particular genetic marker (HLA-DQA1*01) was significantly more common in ME/CFS patients, suggesting genes may play a role in who develops this illness.

E2 ModerateCohortPEM not requiredCross-Sectional

Spinal fluid abnormalities in patients with chronic fatigue syndrome.

Natelson, Benjamin H, Weaver, Shelley A, Tseng, Chin-Lin et al.·Clinical and diagnostic laboratory immunology·2005

Researchers performed spinal taps on 44 ME/CFS patients and 13 healthy people to look for signs of brain inflammation. They found that 30% of ME/CFS patients had abnormal levels of white blood cells or proteins in their spinal fluid, compared to none in the healthy group. They also found that certain immune molecules were different in ME/CFS patients, particularly in those with sudden flu-like symptom onset. These results suggest that ME/CFS may involve real physical changes in the nervous system, not just psychological factors.

NeuroinflammationImmune System

E2 ModerateCohortPEM not requiredCase-Control

Increased neutrophil apoptosis in chronic fatigue syndrome.

Kennedy, G, Spence, V, Underwood, C et al.·Journal of clinical pathology·2004

This study found that people with ME/CFS have more dying white blood cells (neutrophils) and fewer healthy ones compared to people without the condition. The researchers also discovered that ME/CFS patients have higher levels of a chemical called TGF-beta1 that can trigger cell death. These findings suggest that ME/CFS involves measurable problems with the immune system that can be detected in a blood test.

E2 ModerateCohortPEM not requiredCross-Sectional

IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome.

Lerner, A Martin, Beqaj, Safedin H, Deeter, Robert G et al.·In vivo (Athens, Greece)·2004

Researchers tested blood samples from 58 ME/CFS patients and 68 healthy controls for antibodies to Epstein-Barr virus (EBV), a common virus that causes mononucleosis. They found that about half of the ME/CFS patients (33 out of 58) had elevated levels of a specific type of antibody called IgM against EBV, while none of the healthy controls had this pattern. These antibody levels stayed elevated in ME/CFS patients for up to 3.5 years, suggesting this test might help identify a particular subgroup of ME/CFS patients.

E2 ModerateCohortPEM not requiredCross-Sectional

Study of immune alterations in patients with chronic fatigue syndrome with different etiologies.

Racciatti, D, Dalessandro, M, Delle Donne, L et al.·International journal of immunopathology and pharmacology·2004

This study looked at immune system cells in people with ME/CFS to see if there were differences compared to healthy people. Researchers tested blood samples from 139 ME/CFS patients and 36 healthy controls, examining specific types of white blood cells. They found that people with ME/CFS had lower counts of certain immune cells, suggesting the immune system may play a role in causing or maintaining the condition.

E2 ModerateBehavioralPEM not requiredObservational

Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies.

Boscarino, Joseph A·Annals of the New York Academy of Sciences·2004

This study looked at whether people with PTSD (post-traumatic stress disorder) are more likely to develop physical illnesses, including chronic fatigue syndrome. Researchers examined nearly 2,500 Vietnam veterans and found that those with chronic PTSD had higher rates of autoimmune diseases and showed immune system changes that could explain why trauma survivors develop long-lasting health problems.

E2 ModerateCohortPEM not requiredCross-Sectional

Cellular and humoral immune abnormalities in Gulf War veterans.

Vojdani, Aristo, Thrasher, Jack D·Environmental health perspectives·2004

Researchers compared immune system markers in 100 Gulf War veterans with symptoms to 100 healthy controls. They found that Gulf War veterans had lower natural killer cell activity, higher B cells, more immune complexes, and stronger antibody responses to multiple viruses—changes that persisted 2–8 years after the war. These findings suggest that Gulf War syndrome involves multiple immune system abnormalities similar to those seen in chronic fatigue syndrome.

E2 ModerateCohortPEM not requiredCase-Control

RNase L levels in peripheral blood mononuclear cells: 37-kilodalton/83-kilodalton isoform ratio is a potential test for chronic fatigue syndrome.

Tiev, Kiet Phong, Demettre, Edith, Ercolano, Philippe et al.·Clinical and diagnostic laboratory immunology·2003

This study looked at a protein called RNase L in the immune cells of ME/CFS patients and healthy people. Researchers found that ME/CFS patients had a different pattern of RNase L forms compared to healthy volunteers, and this pattern could potentially be used as a simple blood test to help diagnose ME/CFS. The test showed promise in distinguishing ME/CFS patients from healthy people in this small group.

E2 ModerateCohortPEM unclearObservational

Chronic fatigue syndrome in patients with macrophagic myofasciitis.

Authier, François-Jérôme, Sauvat, Stéphane, Champey, Julien et al.·Arthritis and rheumatism·2003

This study looked at patients with macrophagic myofasciitis (MMF), a rare inflammatory muscle condition, and found that some of them also developed symptoms very similar to chronic fatigue syndrome (ME/CFS). The researchers observed that these patients experienced persistent fatigue, muscle pain, and other symptoms characteristic of ME/CFS alongside their muscle inflammation.

E2 ModerateCohortPEM not requiredCross-Sectional

Enhanced glucocorticoid sensitivity in patients with chronic fatigue syndrome.

Gaab, Jens, Rohleder, Nicolas, Heitz, Vera et al.·Acta neuropsychiatrica·2003

This study looked at how the bodies of ME/CFS patients respond to stress hormones called glucocorticoids (particularly cortisol). Researchers gave 21 ME/CFS patients and 20 healthy people a stressful social task, then measured their cortisol levels and how sensitive their immune cells were to glucocorticoids. They found that ME/CFS patients' immune cells were more sensitive to these stress hormones than healthy people's cells, even though their cortisol levels rose similarly to controls.

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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.