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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

541–560 of 1,198 studies

E2 ModerateCohortPEM not requiredCross-Sectional

Detection of Mycoplasma genus and Mycoplasma fermentans by PCR in patients with Chronic Fatigue Syndrome.

Vojdani, A, Choppa, P C, Tagle, C et al.·FEMS immunology and medical microbiology·1998

Researchers tested blood samples from 100 ME/CFS patients and 50 healthy people to see if a bacterium called Mycoplasma fermentans was present. They found this bacterium's genetic material in more than a third of ME/CFS patients compared to only 8% of healthy controls. Patients with higher amounts of the bacterium also had stronger immune responses against it, suggesting their bodies were reacting to the infection.

E2 ModerateCohortPEM unclearCross-Sectional

[Incidence and clinical relevance of antibodies to phospholipids, serotonin and ganglioside in patients with sudden deafness and progressive inner ear hearing loss].

Heller, U, Becker, E W, Zenner, H P et al.·HNO·1998

This study looked at whether certain antibodies (proteins the immune system makes) are found more often in people with sudden or progressive hearing loss. Researchers found that about half of hearing loss patients had antibodies against phospholipids and about half to two-thirds had antibodies against serotonin and gangliosides. Interestingly, some patients with hearing loss also had symptoms of ME/CFS and fibromyalgia, suggesting these conditions may be connected through shared immune system abnormalities.

E2 ModerateBehavioralPEM not requiredCase-Control

Chronic fatigue syndrome: identification of distinct subgroups on the basis of allergy and psychologic variables.

Borish, L, Schmaling, K, DiClementi, J D et al.·The Journal of allergy and clinical immunology·1998

This study looked at whether allergies and psychological factors play a role in ME/CFS. Researchers compared 18 people with ME/CFS to healthy controls, people with allergies, and people with depression. They found that people with ME/CFS had different immune molecules (called cytokines) in their blood compared to healthy people, similar to those with allergies. Interestingly, people with ME/CFS who also had certain psychological profiles showed different immune patterns, suggesting that both allergies and how the mind responds to them may contribute to ME/CFS in some patients.

E2 ModerateCohortPEM unclearCross-Sectional

Nasal secretion analysis in allergic rhinitis, cystic fibrosis, and nonallergic fibromyalgia/chronic fatigue syndrome subjects.

Baraniuk, J N, Clauw, D, Yuta, A et al.·American journal of rhinology·1998

Many people with ME/CFS experience nasal congestion and rhinitis symptoms, but don't test positive for allergies. This study analyzed nasal fluid from ME/CFS patients and compared it to people with allergies, cystic fibrosis, and healthy controls to understand what might be causing these symptoms. The researchers found that ME/CFS patients' nasal fluid looked similar to healthy controls, suggesting that the constant baseline secretion processes in the nose are not abnormal in ME/CFS.

E2 ModerateCohortPEM not requiredCase-Control

Yersinia enterocolitica and the chronic fatigue syndrome.

Swanink, C M, Stolk-Engelaar, V M, van der Meer, J W et al.·The Journal of infection·1998

This study looked for signs that a bacterium called Yersinia enterocolitica might cause ME/CFS by testing blood samples from 88 ME/CFS patients and 77 healthy people. Researchers found that antibodies (immune markers) to this bacterium were equally common in both groups, suggesting this particular infection is unlikely to be a major cause of ME/CFS.

E2 ModerateCohortPEM not requiredCross-Sectional

Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis.

Natelson, B H, LaManca, J J, Denny, T N et al.·The American journal of medicine·1998

Researchers compared blood immune system markers between ME/CFS patients, people with depression, people with multiple sclerosis, and healthy controls. They measured 18 different immune system measurements, looking for signs that ME/CFS involves immune system problems. The study found only minor differences in one immune protein between ME/CFS patients and healthy controls, and these differences disappeared when comparing across all three disease groups.

E2 ModerateCohortPEM not requiredCross-Sectional

Rhinitis symptoms in chronic fatigue syndrome.

Baraniuk, J N, Clauw, D J, Gaumond, E·Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology·1998

This study looked at whether people with ME/CFS have more nasal and sinus problems than the general population. Researchers compared 51 ME/CFS patients with healthy controls and people with allergies, using questionnaires and allergy skin tests. They found that most ME/CFS patients reported significant nasal and sinus symptoms, but about half of these cases appeared to be non-allergic in nature.

E2 ModerateCohortPEM unclearCase-Control

Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.

Bennett, A L, Chao, C C, Hu, S et al.·Journal of clinical immunology·1997

Researchers measured a protein called TGF-beta in the blood of ME/CFS patients and compared it to healthy people and patients with other diseases like lupus and multiple sclerosis. They found that ME/CFS patients had significantly higher levels of this protein than all the other groups studied. This suggests that TGF-beta might play a role in ME/CFS, though more research is needed to understand exactly how.

E2 ModerateCohortPEM not requiredCross-Sectional

High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome.

von Mikecz, A, Konstantinov, K, Buchwald, D S et al.·Arthritis and rheumatism·1997

Researchers tested blood samples from 60 ME/CFS patients and found that 83% had unusual antibodies (immune proteins) attacking their own cells—specifically targeting proteins that form the structural framework inside and around cell nuclei. These antibodies were rarely seen in healthy people (only 17%), suggesting this autoimmune pattern might be unique to ME/CFS and could potentially help doctors identify the disease.

E2 ModerateCohortPEM not requiredObservational

Chronic fatigue syndrome.

Mawle, A C·Immunological investigations·1997

This study examined whether ME/CFS might be caused by an infection or involve immune system problems. While researchers didn't find a specific virus or bacteria responsible for the illness, they discovered that when they grouped patients based on whether their symptoms started suddenly or gradually, some differences in immune markers appeared between patients and healthy people.

E2 ModerateCohortPEM not requiredCross-Sectional

Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome.

Buchwald, D, Wener, M H, Pearlman, T et al.·The Journal of rheumatology·1997

Researchers tested blood samples from 153 patients with severe fatigue to see if certain immune markers were elevated, thinking that an overactive immune system might cause ME/CFS. They found that three markers (C-reactive protein, beta 2-microglobulin, and neopterin) were higher in fatigued patients compared to healthy controls, but these markers couldn't reliably distinguish between ME/CFS and other types of chronic fatigue. The results suggest that some patients have signs of immune activation, but it's unclear whether this is a temporary response to infection or part of the ongoing illness.

E2 ModerateCohortPEM not requiredObservational

[Demonstration on Borna disease virus in patients with chronic fatigue syndrome].

Nakaya, T, Kuratsune, H, Kitani, T et al.·Nihon rinsho. Japanese journal of clinical medicine·1997

Researchers tested whether a virus called Borna disease virus (BDV) might be connected to ME/CFS. They found that some patients with ME/CFS had signs of BDV infection, and the virus was also detected in one family where multiple members had ME/CFS. While these findings suggest BDV could play a role, the study shows it's likely not the sole cause of ME/CFS.

E2 ModerateCohortPEM not requiredCross-Sectional

[High prevalence without reactivation of herpes virus 6 in subjects with chronic fatigue syndrome].

Cuende, J I, Civeira, P, Diez, N et al.·Anales de medicina interna (Madrid, Spain : 1984)·1997

Researchers tested 20 ME/CFS patients for active herpesvirus-6 (HHV-6) infection, a virus that had been suspected as a possible cause of ME/CFS. They found that half the patients had antibodies showing past HHV-6 infection, but sensitive testing detected only small amounts of viral DNA in blood cells and no active viral replication. This suggests that while many ME/CFS patients may have been infected with HHV-6 in the past, the virus is not actively multiplying in their bodies.

E2 ModerateCohortPEM not requiredCase-Control

Immune responses associated with chronic fatigue syndrome: a case-control study.

Mawle, A C, Nisenbaum, R, Dobbins, J G et al.·The Journal of infectious diseases·1997

Researchers compared immune system measurements between ME/CFS patients and healthy controls to see if immune differences could reliably detect the illness. While previous studies reported many immune differences, this careful study found most standard immune tests showed no difference between patients and controls. However, when they looked at specific subgroups—such as patients whose illness started suddenly versus gradually—they did find some immune differences, suggesting that ME/CFS may not be a single uniform immune condition.

E2 ModerateCohortPEM not requiredCase-Control

Electron microscopic immunocytological profiles in chronic fatigue syndrome.

Holmes, M J, Diack, D S, Easingwood, R A et al.·Journal of psychiatric research·1997

Researchers used a special microscope to examine immune cells from ME/CFS patients and found structures that resembled a type of virus in 10 out of 17 patients, but not in healthy control subjects. However, when they tried to confirm this finding using additional testing methods, the results were unclear. This suggests something might be different in the cells of some ME/CFS patients, but more research is needed to understand what it means.

E2 ModerateCohortPEM not requiredCross-Sectional

Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome.

Swanink, C M, Vercoulen, J H, Galama, J M et al.·The Journal of infectious diseases·1996

This study compared immune system markers in blood samples from 76 ME/CFS patients and 69 healthy controls to see if immune abnormalities could explain fatigue severity. Researchers found one immune marker (CD11b on CD8 cells) was lower in ME/CFS patients, but most other immune measures were similar between groups, and none of these markers correlated with how severe a patient's fatigue or depression was.

E2 ModerateCohortPEM not requiredObservational

Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome.

Kitani, T, Kuratsune, H, Fuke, I et al.·Microbiology and immunology·1996

This 1996 study investigated whether a virus called Borna disease virus (BDV) might be connected to chronic fatigue syndrome (ME/CFS). Borna disease virus naturally infects animals like horses and sheep, and researchers found evidence of this virus or antibodies to it in some ME/CFS patients. The study suggests there may be a link between BDV infection and ME/CFS symptoms, though more research is needed to understand if and how this virus contributes to the condition.

E2 ModerateCohortPEM not requiredObservational

The influence of age on transfer factor treatment of cellular immunodeficiency, chronic fatigue syndrome and/or chronic viral infections.

Hana, I, Vrubel, J, Pekarek, J et al.·Biotherapy (Dordrecht, Netherlands)·1996

This study looked at 222 patients with weak immune systems, many of whom also had ME/CFS and/or chronic viral infections (EBV or CMV). They were treated with transfer factor, a type of immune-boosting therapy, given as injections over 8 weeks. The researchers found that younger patients improved more often than older patients, with failure rates rising significantly in those over 54 years old.

E2 ModerateCohortPEM not requiredObservational

No findings of enteroviruses in Swedish patients with chronic fatigue syndrome.

Lindh, G, Samuelson, A, Hedlund, K O et al.·Scandinavian journal of infectious diseases·1996

Researchers tested 34 Swedish patients with ME/CFS to see if a virus called enterovirus might be causing their illness. They looked for the virus in stool samples, blood, spinal fluid, and muscle tissue using several different detection methods. The study found no evidence of enterovirus infection in any of the patients tested.

E2 ModerateCohortPEM not requiredObservational

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment.

Kodama, M, Kodama, T, Murakami, M·In vivo (Athens, Greece)·1996

This 1996 study examined whether high-dose vitamin C infusions, with or without a hormone called DHEA added, could help treat ME/CFS. Researchers treated 313 patients with chronic pneumonia-like illness that matched ME/CFS symptoms, often combined with antibiotics. The authors found that the combination of two types of vitamin C infusions worked better than one type alone, suggesting that low levels of certain body hormones might play a role in ME/CFS.

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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.