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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 6,205 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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1205 studies

E0 — Consensus654E1 — Replicated321E2 — Moderate2,807E3 — Preliminary2,423

ME/CFS4,040Long COVID224Post-infectious190Overlapping1,064

Required for diagnosis417Not specified / unclear2,251Not required3,537

Post-Exertional Malaise1,082Cognitive Dysfunction1,749Pain1,628Unrefreshing Sleep805Orthostatic Intolerance484

Cytokines821Gene Expression573Metabolomics477Neuroimaging472Autoantibodies460

Infection-Triggered1,182Long COVID Overlap604Pediatric496Severe232

Strong Phenotyping445Sex-Stratified330Severe ME Included119

Systematic Review272Meta-Analysis61RCT301

Peer-reviewed6,148Preprint3Unclear54

521–540 of 1,205 studies

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 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 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 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 requiredCase-Control

Cellular immunity in monozygotic twins discordant for chronic fatigue syndrome.

Sabath, Daniel E, Barcy, Serge, Koelle, David M et al.·The Journal of infectious diseases·2002

This study looked at immune system differences in identical twins where one twin had ME/CFS and the other didn't. By comparing identical twins, researchers could focus on immune changes related to the illness rather than genetic differences. The study found that certain immune cells were more variable in twins with ME/CFS, suggesting the immune system may be less stable in this condition.

E2 ModerateCohortPEM not requiredCross-Sectional

Prevalence of allergen-specific IgE among patients with chronic fatigue syndrome.

Kowal, Krzysztof, Schacterele, Richard S, Schur, Peter H et al.·Allergy and asthma proceedings·2002

This study tested 50 ME/CFS patients for allergies by measuring specific immune proteins called allergen-specific IgE in their blood. Contrary to earlier patient surveys suggesting very high allergy rates, only 36% of ME/CFS patients had detectable allergic antibodies to common allergens like dust mites, pollen, and foods. This rate was similar to what researchers find in the general healthy population, suggesting that allergies may not be uniquely associated with ME/CFS.

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 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 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 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 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 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 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.

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 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.

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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.