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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

501–520 of 1,186 studies

E2 ModerateCohortPEM not requiredLongitudinal

Chronic fatigue syndrome and arthralgia following parvovirus B19 infection.

Kerr, Jonathan R, Bracewell, Janice, Laing, Ian et al.·The Journal of rheumatology·2002

This study looked at whether parvovirus B19 infection (a common virus that causes rash and joint pain) can lead to chronic fatigue syndrome (CFS). Researchers followed 51 patients with acute B19 infection and found that some developed lasting joint pain and fatigue months later. Five patients met the diagnostic criteria for CFS after B19 infection, but the study found it very difficult to prove that B19 was the cause without clear evidence of infection at the time fatigue started.

E2 ModerateCohortPEM not requiredCase-Control

Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome.

Vernon, Suzanne D, Unger, Elizabeth R, Dimulescu, Irina M et al.·Disease markers·2002

Researchers examined blood cells from people with ME/CFS and healthy volunteers to see if they could find differences in how genes are turned on or off. They found that blood cells from ME/CFS patients showed different gene activity patterns compared to healthy people, and some of these differences involved immune system genes. This suggests that ME/CFS involves problems with how the immune system is functioning.

BiomarkersImmune System

E2 ModerateCohortPEM not requiredCase-Control

IgM serum antibodies to human cytomegalovirus nonstructural gene products p52 and CM2(UL44 and UL57) are uniquely present in a subset of patients with chronic fatigue syndrome.

Lerner, A Martin, Beqaj, Safedin H, Deeter, Robert G et al.·In vivo (Athens, Greece)·2002

Researchers tested blood samples from ME/CFS patients and healthy controls for specific antibodies to cytomegalovirus (CMV), a common virus. They found that 16 ME/CFS patients had unique antibodies to two CMV proteins (p52 and CM2) that were not found in 77 control subjects, including other ME/CFS patients and healthy people. This suggests these antibodies might be a specific marker for a subset of ME/CFS patients and could indicate an ongoing or incomplete CMV infection in this group.

E2 ModerateCohortPEM unclearCross-Sectional

Antinuclear autoantibodies (ANA) in Gulf War-related illness and chronic fatigue syndrome (CFS) patients.

Skowera, A, Stewart, E, Davis, E T et al.·Clinical and experimental immunology·2002

This study looked for a specific type of immune protein called antinuclear autoantibodies (ANAs) in people with ME/CFS and Gulf War veterans with multiple symptoms. Researchers compared blood samples from ME/CFS patients, symptomatic Gulf War veterans, and healthy controls. They found no significant differences in ANA levels between any of the groups, and none of the patients had the specific nuclear envelope ANA type that had been suggested as a possible ME/CFS marker.

E2 ModerateCohortPEM not requiredCross-Sectional

Cytokines in nasal lavage fluids from acute sinusitis, allergic rhinitis, and chronic fatigue syndrome subjects.

Repka-Ramirez, Susana, Naranch, Kristina, Park, Yong-Jin et al.·Allergy and asthma proceedings·2002

Researchers measured inflammation markers in nasal fluid samples from people with ME/CFS, allergic rhinitis, acute sinusitis, and healthy controls. They found that people with acute sinusitis had significantly higher levels of inflammatory substances, but people with ME/CFS did not show elevated inflammation in their nasal passages compared to healthy controls.

E2 ModerateCohortPEM unclearCross-Sectional

Immunological variables mediate cognitive dysfunction in gulf war veterans but not civilians with chronic fatigue syndrome.

Brimacombe, Michael, Zhang, QuanWu, Lange, Gudrun et al.·Neuroimmunomodulation·2002

This study compared immune system markers and thinking/memory problems in Gulf War veterans with ME/CFS and civilians with ME/CFS. The researchers found that in Gulf War veterans, certain immune system patterns were connected to cognitive problems like slower reaction times, and these immune changes seemed to affect how well they could function. Interestingly, this same immune-cognition relationship was not found in civilians with ME/CFS, suggesting the two groups may have different underlying causes for their illness.

E2 ModerateReviewPEM not requiredReview-Narrative

Influenza vaccination: is it appropriate in chronic fatigue syndrome?

Sleigh, Kenna M, Marra, Fawziah H, Stiver, H Grant·American journal of respiratory medicine : drugs, devices, and other interventions·2002

This study looked at whether people with ME/CFS should get the flu vaccine, since many patients worry it might worsen their symptoms or harm their already-altered immune system. Researchers reviewed patient concerns and clinical trial data and found that flu vaccination actually produces protective antibodies in ME/CFS patients without making their symptoms worse, though some patients reported more side effects after the shot (which turned out to overlap with ME/CFS symptoms they already had).

E2 ModerateCohortPEM unclearCase-Control

Chronic fatigue syndrome and immune dysfunction: cause or effect?

Pollack, Shimon·The Israel Medical Association journal : IMAJ·2002

This study examined whether immune system problems in ME/CFS patients are a cause of the illness or a result of having the illness. Researchers compared immune markers between people with ME/CFS and healthy controls to understand this relationship better. The study helps clarify an important question: does a faulty immune system trigger ME/CFS, or does having ME/CFS damage the immune system over time?

E2 ModerateCohortPEM not requiredCross-Sectional

High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.

Sinaii, N, Cleary, S D, Ballweg, M L et al.·Human reproduction (Oxford, England)·2002

This study found that women with endometriosis—a painful condition where tissue grows outside the uterus—have much higher rates of ME/CFS, fibromyalgia, and autoimmune diseases compared to the general population. Researchers surveyed nearly 3,700 women with endometriosis and compared their health conditions to published data about women without endometriosis. Women with endometriosis were 150 times more likely to have ME/CFS and nearly twice as likely to have fibromyalgia.

E2 ModerateCohortPEM not requiredCross-Sectional

A biochemical analysis of people with chronic fatigue who have Irlen Syndrome: speculation concerning immune system dysfunction.

Robinson, G L, McGregor, N R, Roberts, T K et al.·Perceptual and motor skills·2001

This study looked at 61 people with ME/CFS to see if they also had a visual processing problem called Irlen Syndrome (where certain patterns and lighting cause visual discomfort). Researchers found that people with more severe visual problems had different levels of certain fats and amino acids in their blood and urine compared to those with milder visual symptoms. The authors suggest these differences might show signs of immune system activation, possibly from an infection.

Energy MetabolismImmune System

E2 ModerateCohortPEM not requiredCross-Sectional

IgE levels are the same in chronic fatigue syndrome (CFS) and control subjects when stratified by allergy skin test results and rhinitis types.

Repka-Ramirez, M S, Naranch, K, Park, Y J et al.·Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology·2001

Researchers tested whether people with ME/CFS have higher levels of IgE, a protein the immune system makes during allergic reactions. They compared IgE levels in 95 ME/CFS patients and 109 healthy people, including those with and without allergies. They found IgE levels were the same in both groups, suggesting that allergies are probably not a major cause of ME/CFS.

E2 ModerateCohortPEM not requiredCase-Control

Lack of association between HLA genotype and chronic fatigue syndrome.

Underhill, J A, Mahalingam, M, Peakman, M et al.·European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics·2001

Researchers tested whether certain immune system genes (HLA genes) were more common in ME/CFS patients compared to healthy people. They studied 58 ME/CFS patients and 134 healthy controls using modern genetic testing methods. They found no significant differences in HLA genes between the two groups, suggesting that these particular immune genes are not a major cause of ME/CFS.

E2 ModerateCohortPEM not requiredObservational

Antiviral pathway activation in patients with chronic fatigue syndrome and acute infection.

Gow, J W, Simpson, K, Behan, P O et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·2001

Researchers compared two immune system defense pathways (RNase L and PKR) in people with ME/CFS, people with acute stomach infections, and healthy people. The immune pathways were only activated in people with acute infections, not in people with ME/CFS or healthy controls. This finding suggests that these particular immune markers cannot be used as a simple diagnostic test for ME/CFS.

E2 ModerateCohortPEM not requiredObservational

The biochemical study of intermaxillary fixation (IMF) stress in oral surgery inpatients.

Sakaino, H·The Kurume medical journal·2001

This study looked at how oral surgery patients respond to intermaxillary fixation (IMF), a procedure that temporarily wires the jaw shut. Researchers measured stress hormones in urine and found that IMF causes significant stress, leading to irritability and sleep problems. When patients were given an anti-anxiety medication, their stress hormone levels were reduced.

E2 ModerateCohortPEM not requiredCase-Control

Salivary gland changes in chronic fatigue syndrome: a case-controlled preliminary histologic study.

Woo, S B, Schacterle, R S, Komaroff, A L et al.·Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics·2000

Researchers examined tiny salivary glands in the lips of 11 ME/CFS patients and compared them to healthy controls. They found that ME/CFS patients had various changes in these glands, including swelling, scarring, and immune cell infiltration. Most notably, ME/CFS patients had significantly more mast cells (immune cells) in their salivary glands than controls, suggesting these glands may be damaged in ME/CFS.

E2 ModerateCohortPEM unclearCase-Control

A 37 kDa 2-5A binding protein as a potential biochemical marker for chronic fatigue syndrome.

De Meirleir, K, Bisbal, C, Campine, I et al.·The American journal of medicine·2000

Researchers found a specific protein (37 kDa) in the blood cells of 88% of ME/CFS patients, compared to only 28% of control subjects. This protein was present in much higher amounts in ME/CFS patients, suggesting it could potentially be used as a blood test to help identify the condition.

BiomarkersImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Antibodies to squalene in Gulf War syndrome.

Asa, P B, Cao, Y, Garry, R F·Experimental and molecular pathology·2000

Researchers tested whether Gulf War veterans with illness had antibodies (immune proteins) against a substance called squalene in their blood. They found that 95% of sick Gulf War veterans had these antibodies, while veterans who served but stayed healthy had none. Interestingly, even military personnel who were vaccinated for the Gulf War but never deployed also had these antibodies if they developed the same symptoms.

E2 ModerateCohortPEM unclearObservational

Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients.

Ablashi, D V, Eastman, H B, Owen, C B et al.·Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology·2000

This study looked at whether a common virus called HHV-6 might be reactivated in ME/CFS patients. Researchers found that ME/CFS and MS patients had higher levels of antibodies (immune markers) to HHV-6 compared to healthy people, and they detected active virus in blood cells from these patients. The findings suggest that HHV-6 reactivation might play a role in causing or worsening ME/CFS symptoms.

E2 ModerateCohortPEM not requiredLongitudinal

Antibodies to parvovirus B19 non-structural protein are associated with chronic but not acute arthritis following B19 infection.

Kerr, J R, Cunniffe, V S·Rheumatology (Oxford, England)·2000

This study tracked people who had parvovirus B19 infection to see if certain antibodies (immune proteins) in their blood were linked to lasting joint pain and arthritis. Researchers found that antibodies to a specific viral protein called NS1 were more common in people who developed chronic arthritis months or years after the infection, but were not associated with arthritis during the acute illness itself.

E2 ModerateCohortPEM not requiredCase-Control

Mercury and nickel allergy: risk factors in fatigue and autoimmunity.

Sterzl, Ivan, Procházková, Jarmila, Hrdá, Pavlína et al.·Neuro endocrinology letters·1999

This study tested whether allergies to metals like mercury (found in old dental fillings) and nickel might trigger fatigue and autoimmune problems in people with ME/CFS. Researchers compared three groups of tired patients with healthy controls and found that people with fatigue were more sensitive to these metals. When some patients had their mercury-containing fillings removed and replaced, their fatigue improved significantly.

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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.