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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 6,122 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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1186 studies

E0 — Consensus629E1 — Replicated319E2 — Moderate2,758E3 — Preliminary2,416

ME/CFS4,010Long COVID209Post-infectious188Overlapping1,031

Required for diagnosis409Not specified / unclear2,191Not required3,522

Post-Exertional Malaise1,040Cognitive Dysfunction1,712Pain1,606Unrefreshing Sleep787Orthostatic Intolerance470

Cytokines813Gene Expression564Metabolomics469Neuroimaging464Autoantibodies455

Infection-Triggered1,159Long COVID Overlap564Pediatric494Severe227

Strong Phenotyping428Sex-Stratified325Severe ME Included115

Systematic Review256Meta-Analysis60RCT299

Peer-reviewed6,065Preprint3Unclear54

541–560 of 1,186 studies

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 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 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 unclearCross-Sectional

Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.

Buchwald, D, Ashley, R L, Pearlman, T et al.·Journal of medical virology·1996

Researchers tested 548 people with chronic fatigue to see if they had unusually high levels of antibodies to 13 common viruses, since ME/CFS often starts suddenly after a viral illness. They compared antibody levels in patients with chronic fatigue to healthy controls and found no consistent differences between the groups, suggesting these particular virus tests are not helpful in diagnosing or understanding chronic fatigue.

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

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 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

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 requiredCross-Sectional

Eosinophil cationic protein serum levels and allergy in chronic fatigue syndrome.

Conti, F, Magrini, L, Priori, R et al.·Allergy·1996

This study measured a protein called eosinophil cationic protein (ECP) in the blood of ME/CFS patients to see if their immune cells called eosinophils were overly active. Researchers found that ME/CFS patients had significantly higher ECP levels than healthy controls, and most ME/CFS patients also tested positive for allergies. However, ME/CFS patients with allergies did not have higher ECP levels than those without allergies, suggesting the connection may be more complex than initially expected.

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.

E2 ModerateCohortPEM unclearCross-Sectional

High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders.

Klein, R, Berg, P A·European journal of medical research·1995

Researchers found that patients with ME/CFS and fibromyalgia syndrome (FMS) often have similar antibodies in their blood—proteins the immune system produces that may attack the body's own tissues. About 62% of ME/CFS patients and 73% of FMS patients had antibodies against serotonin, a chemical important for mood and pain regulation. Interestingly, these antibodies were also found in family members of affected patients, suggesting a genetic component may play a role.

E2 ModerateCohortPEM not requiredCross-Sectional

Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome.

Di Luca, D, Zorzenon, M, Mirandola, P et al.·Journal of clinical microbiology·1995

Researchers looked for two common viruses (HHV-6 and HHV-7) in immune cells of ME/CFS patients and compared them to healthy people. They found that HHV-7 was equally common in both groups, but a specific type of HHV-6 called variant A was found more often in ME/CFS patients. This suggests that HHV-6 variant A may be connected to ME/CFS, though the study does not prove it causes the illness.

E2 ModerateCohortPEM not requiredObservational

Cell-mediated immune function and the outcome of chronic fatigue syndrome.

Wilson, A, Hickie, I, Lloyd, A et al.·International journal of immunopharmacology·1995

Researchers followed 103 ME/CFS patients for an average of 3.2 years to see if their immune system function predicted how well they would recover. Most patients improved over time, but about one-third remained unable to work. The study found that immune cell measurements taken at the start did not seem to predict who would get better or worse.

E2 ModerateCohortPEM not requiredCross-Sectional

Silicone breast implant--associated musculoskeletal manifestations.

Cuellar, M L, Gluck, O, Molina, J F et al.·Clinical rheumatology·1995

This study looked at 300 women with silicone breast implants who came to a rheumatology clinic with muscle and joint pain. The researchers found that over 80% of these women had signs of connective tissue disease, and more than half met criteria for fibromyalgia or chronic fatigue syndrome. When some women had their implants removed, over 70% reported improvement in their overall symptoms.

E2 ModerateCohortPEM not requiredCase-Control

Seroepidemiology of chronic fatigue syndrome: a case-control study.

Mawle, A C, Nisenbaum, R, Dobbins, J G et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1995

Researchers tested people with ME/CFS and healthy control groups for antibodies to many common viruses, including herpesviruses and enteroviruses. They found no differences between the two groups—patients with ME/CFS did not have higher levels of antibodies to any of the viruses tested. This suggests that recent or past infection with these particular viruses is not a distinguishing feature of ME/CFS.

E2 ModerateCohortPEM not requiredCross-Sectional

Abnormalities of carnitine metabolism in chronic fatigue syndrome.

Majeed, T, de Simone, C, Famularo, G et al.·European journal of neurology·1995

This study examined carnitine, a substance that helps cells produce energy, in people with ME/CFS. Researchers found that while carnitine levels in the blood were normal, the levels inside immune cells were significantly lower in ME/CFS patients compared to healthy people. This finding suggests that ME/CFS patients might benefit from taking carnitine supplements to restore normal energy production.

E2 ModerateCohortPEM unclearCase-Control

Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome.

Sairenji, T, Yamanishi, K, Tachibana, Y et al.·Intervirology·1995

This study measured antibodies to three viruses (EBV, HHV-6, and HHV-7) in the blood of ME/CFS patients and healthy controls. Researchers observed that ME/CFS patients had higher antibody levels to all three viruses compared to controls, particularly antibodies to EBV's ZEBRA protein. These findings are consistent with the hypothesis that viral reactivation may occur in ME/CFS, though the study does not establish whether this is a cause or consequence of the illness.

E2 ModerateCohortPEM not requiredCross-Sectional

Prevalence of IgM antibodies to human herpesvirus 6 early antigen (p41/38) in patients with chronic fatigue syndrome.

Patnaik, M, Komaroff, A L, Conley, E et al.·The Journal of infectious diseases·1995

Researchers tested whether people with ME/CFS have more signs of a virus called human herpesvirus 6 (HHV-6) compared to healthy people. They found that 77% of ME/CFS patients had antibodies suggesting exposure to or active HHV-6 infection, compared to only 12% of healthy controls. This suggests HHV-6 may be more common in people with ME/CFS, though it's unclear whether the virus causes the illness or is simply more active in these patients.

E2 ModerateCohortPEM not requiredCross-Sectional

Frequency of deviant immunological test values in chronic fatigue syndrome patients.

Natelson, B H, Ellis, S P, Braonáin, P J et al.·Clinical and diagnostic laboratory immunology·1995

Researchers tested 11 different immune system markers in ME/CFS patients and compared them to fatigued people without ME/CFS. They found that three immune tests (protein A binding, Raji cell test, and complement proteins C3 or C4) showed different results between the groups. However, most other immune tests they looked at, including antibody levels and other complement markers, did not reliably distinguish ME/CFS patients from those with other causes of fatigue.

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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.