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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

521–540 of 1,186 studies

E2 ModerateCohortPEM not requiredCross-Sectional

TNF-alpha and chronic fatigue syndrome.

Moss, R B, Mercandetti, A, Vojdani, A·Journal of clinical immunology·1999

This study looked at whether a molecule called TNF-alpha, which helps control inflammation in the body, is elevated in people with ME/CFS. Researchers compared blood levels of TNF-alpha in patients with ME/CFS to healthy people without the condition. They found that people with ME/CFS had significantly higher levels of TNF-alpha, suggesting that inflammation may play a role in the disease.

E2 ModerateCohortPEM unclearCase-Control

Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome.

Zhang, Q, Zhou, X D, Denny, T et al.·Clinical and diagnostic laboratory immunology·1999

This study compared immune system markers in people with ME/CFS, looking separately at Gulf War veterans and non-veterans. Researchers found that Gulf War veterans with ME/CFS had different immune patterns (more of certain types of T cells, fewer NK cells, and higher levels of inflammation markers) compared to healthy veterans. However, non-veterans with ME/CFS showed no such immune differences from healthy controls, suggesting Gulf War service may have affected the immune system differently than sporadic ME/CFS.

E2 ModerateCohortPEM not requiredCase-Control

Is depression associated with immune activation?

Natelson, B H, Denny, T, Zhou, X D et al.·Journal of affective disorders·1999

Researchers tested whether depression and ME/CFS are caused by an overactive immune system. They compared immune cell counts and immune signaling molecules in people with depression, people with ME/CFS who later developed depression, and healthy controls. Surprisingly, they found no signs of immune activation in either patient group—instead, the data suggested the immune system was actually downregulated (less active) in people with depression.

E2 ModerateCohortPEM not requiredCase-Control

Chronic fatigue syndrome and nickel allergy.

Marcusson, J A, Lindh, G, Evengård, B·Contact dermatitis·1999

This study tested 50 patients with ME/CFS and 73 healthy people for allergic reactions to eight different metals. Researchers found that people with ME/CFS were more likely to be allergic to nickel—36% of ME/CFS patients had nickel allergies compared to only 19% of healthy people. This difference was especially pronounced in women with ME/CFS, where over half (52%) showed nickel allergy. The researchers suggest that nickel exposure might somehow trigger or contribute to ME/CFS in some people.

E2 ModerateCohortPEM not requiredObservational

Metal-specific lymphocytes: biomarkers of sensitivity in man.

Stejskal, Vera DM, Danersund, Antero, Lindvall, Anders et al.·Neuro endocrinology letters·1999

This study tested whether people with ME/CFS-like symptoms had immune reactions to metals in their dental fillings and other restorations. Researchers found that many patients had immune cells that reacted to metals like mercury, nickel, and gold, and that 76% of patients who replaced their metal restorations with non-metal alternatives reported feeling better. The study suggests that metal sensitivity might trigger inflammatory responses that contribute to chronic fatigue and related conditions.

E2 ModerateCohortPEM not requiredObservational

Human herpesviruses in chronic fatigue syndrome.

Wallace, H L, Natelson, B, Gause, W et al.·Clinical and diagnostic laboratory immunology·1999

Researchers tested whether common viruses (HHV6, HHV7, Epstein-Barr virus, and cytomegalovirus) are more active or present in people with ME/CFS compared to healthy people. They examined blood samples from ME/CFS patients and matched healthy controls, looking for both the viruses themselves and antibodies (immune markers) against these viruses. They found no significant differences between the two groups, suggesting these particular viruses may not be a primary driver of ME/CFS.

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 ModerateCohortPEM not requiredObservational

A study of the immunology of the chronic fatigue syndrome: correlation of immunologic parameters to health dysfunction.

Hassan, I S, Bannister, B A, Akbar, A et al.·Clinical immunology and immunopathology·1998

This study examined immune system markers in 44 people with ME/CFS to see how these markers related to symptom severity and mental health. Researchers found that ME/CFS patients had unusual patterns in their immune cells—specifically, signs of increased immune activation and changes in how lymphocytes (white blood cells) behave. These immune changes correlated with worse physical function, pain, and mental health symptoms.

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 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 requiredCross-Sectional

Serum neopterin and somatization in women with chemical intolerance, depressives, and normals.

Bell, I R, Patarca, R, Baldwin, C M et al.·Neuropsychobiology·1998

This study looked at a marker in the blood called neopterin, which may indicate immune system activation, in women with chemical sensitivity (difficulty tolerating everyday chemicals at low levels), women with depression, and healthy women. The researchers found that neopterin levels themselves were similar across groups, but in women with chemical sensitivity, higher neopterin levels were linked with more physical symptoms—a connection not seen in the other groups.

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 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 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 not requiredCase-Control

Reproductive correlates of chronic fatigue syndrome.

Harlow, B L, Signorello, L B, Hall, J E et al.·The American journal of medicine·1998

This study compared reproductive and menstrual histories in women with ME/CFS to healthy women without the condition. Women with ME/CFS reported more gynecologic problems and irregular menstrual cycles, and researchers found signs suggesting ovarian dysfunction—such as polycystic ovary syndrome (PCOS)—occurred more often in the ME/CFS group. The authors propose that hormonal imbalances affecting egg release may contribute to ME/CFS by reducing protective immune effects from certain hormones.

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 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

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 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 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.

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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.