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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

561–580 of 1,186 studies

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

[Chronic fatigue syndrome--a controlled cross-sectional study].

Rasmussen, A K, Nielsen, H, Andersen, V et al.·Ugeskrift for laeger·1994

This study compared immune system markers in 21 people with ME/CFS to 21 healthy people matched by age and sex. Researchers found that certain immune cells in ME/CFS patients produced higher levels of specific immune signaling molecules, while antibody levels were slightly lower than normal. Overall, the study did not find clear evidence that ME/CFS is caused by a persistent viral infection or a severely damaged immune system.

E2 ModerateCohortPEM not requiredCross-Sectional

Immunological abnormalities in patients with chronic fatigue syndrome.

Tirelli, U, Marotta, G, Improta, S et al.·Scandinavian journal of immunology·1994

Researchers studied 265 ME/CFS patients and found unusual patterns in their immune cells compared to healthy people. They discovered that certain types of white blood cells called natural killer (NK) cells and B cells were abnormally increased, and these cells showed signs of being overly activated. These immune abnormalities appeared consistent with what other researchers had found in different countries.

E2 ModerateCohortPEM not requiredCross-Sectional

[Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes].

Hilgers, A, Frank, J·Wiener medizinische Wochenschrift (1946)·1994

This study examined 375 patients with ME/CFS to understand what goes wrong with their immune systems and which infections might be involved. Researchers found that most patients had problems with immune cell function, signs of past viral infections (especially Epstein-Barr virus), and imbalances in immune chemicals. The study suggests ME/CFS may be connected to autoimmune problems and multiple infections.

E2 ModerateCohortPEM not requiredCross-Sectional

[Viral infection and fibromyalgia].

Branco, J C, Tavares, V, Abreu, I et al.·Acta medica portuguesa·1994

This study looked at whether a common virus called parvovirus B19 might be responsible for fibromyalgia, a condition similar to ME/CFS that causes widespread pain and fatigue. Researchers compared blood antibodies (which show past infection) in 52 fibromyalgia patients versus 39 healthy people. They found slightly higher rates of past parvovirus infection in fibromyalgia patients, but the difference was too small to be meaningful, so they concluded the virus is probably not the cause of fibromyalgia.

E2 ModerateCohortPEM not requiredCase-Control

Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?

Manian, F A·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study looked at whether people with ME/CFS have higher levels of antibodies (immune proteins that fight viruses) to multiple different viruses compared to healthy people. Researchers tested blood samples from 20 ME/CFS patients and 20 healthy controls for antibodies to five different viruses. They found that most ME/CFS patients had elevated antibodies to at least one virus, but the pattern didn't suggest a generalized immune overreaction affecting all viruses equally.

E2 ModerateCohortPEM not requiredCross-Sectional

High titers of anti-Epstein-Barr virus DNA polymerase are found in patients with severe fatiguing illness.

Natelson, B H, Ye, N, Moul, D E et al.·Journal of medical virology·1994

This study looked for specific antibodies (proteins the immune system makes) against Epstein-Barr virus (EBV) in people with ME/CFS compared to healthy people. Researchers found that abnormal levels of these antibodies were twice as common in ME/CFS patients, and the effect was even stronger in sicker patients. This suggests these antibodies might help doctors identify which ME/CFS patients have more severe illness.

E2 ModerateCohortPEM not requiredCase-Control

Prevalence of human herpesvirus 6 variants A and B in patients with chronic fatigue syndrome.

Yalcin, S, Kuratsune, H, Yamaguchi, K et al.·Microbiology and immunology·1994

Researchers tested blood samples from 13 ME/CFS patients and 13 healthy people to see if they carried human herpesvirus 6 (HHV-6), a common virus that most people encounter in childhood. They found that over half of the ME/CFS patients had active HHV-6 in their blood, while none of the healthy controls did. The patients also had higher antibody levels, suggesting their immune systems were actively fighting the virus.

E2 ModerateCohortPEM not requiredCross-Sectional

Chronic fatigue syndrome--a controlled cross sectional study.

Rasmussen, A K, Nielsen, H, Andersen, V et al.·The Journal of rheumatology·1994

Researchers compared immune system markers in 21 people with ME/CFS to 21 healthy controls to see if immune problems might cause the illness. They found that people with ME/CFS produced higher levels of certain immune signaling molecules and had slightly different antibody patterns, but overall immune system differences between the groups were small. The study suggests the immune system may be out of balance in ME/CFS, but doesn't prove this imbalance actually causes the disease.

E2 ModerateBehavioralPEM not requiredCross-Sectional

Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome.

Masuda, A, Nozoe, S I, Matsuyama, T et al.·Psychosomatic medicine·1994

This study compared immune system function and psychological stress levels in three groups: healthy people, those with chronic fatigue (but not ME/CFS), and patients with ME/CFS. All three groups showed differences in how stressed they felt, their activity levels, and how well their immune cells (specifically natural killer cells) worked. Importantly, the chronic fatigue group fell somewhere between healthy people and ME/CFS patients in terms of both psychological stress and immune function.

E2 ModerateCohortPEM not requiredCross-Sectional

A potential role for human herpesvirus type 6 in nervous system disease.

Wilborn, F, Schmidt, C A, Brinkmann, V et al.·Journal of neuroimmunology·1994

This study looked for evidence that human herpesvirus type 6 (HHV-6), a common virus, might be involved in nervous system diseases including ME/CFS. Researchers tested blood and spinal fluid samples from patients with different neurological conditions and compared them to healthy controls. They found that a small number of multiple sclerosis patients had HHV-6 DNA in their spinal fluid, and MS patients had higher antibodies to HHV-6 in their blood, suggesting the virus may play a role in that disease.

E2 ModerateCohortPEM not requiredObservational

Epstein-Barr virus infection in Desert Storm reservists.

Carver, L A, Connallon, P F, Flanigan, S J et al.·Military medicine·1994

This study looked at U.S. Army reservists who developed ME/CFS-like symptoms after returning from the Gulf War. Researchers tested 37 of these service members for Epstein-Barr virus (a common virus that can reactivate in the body) and found that 73% had signs of either a new or reactivated infection. This suggests that viral infections might be making ME/CFS symptoms worse or last longer in some people.

E2 ModerateCohortPEM not requiredCross-Sectional

Immunologic abnormalities associated with chronic fatigue syndrome.

Barker, E, Fujimura, S F, Fadem, M B et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study examined immune cells in the blood of ME/CFS patients and compared them to healthy people. Researchers found that ME/CFS patients had normal numbers of immune cells overall, but the cells showed signs of being overactive and tired. Most notably, patients had significantly reduced natural killer cell activity—these are immune cells that normally help fight infections and abnormal cells.

E2 ModeratePEM not requiredRegistry-Resource

An approach to studies of cancer subsequent to clusters of chronic fatigue syndrome: use of data from the Nevada State Cancer Registry.

Levine, P H, Atherton, M, Fears, T et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study looked at whether people in Nevada who developed a CFS-like illness in the mid-1980s had higher rates of cancer, particularly brain tumors and lymphoma, in the years that followed. Researchers checked cancer registry records to see if there was a connection. They found a slight increase in brain tumors but no clear pattern for lymphoma, though they noted the brain tumor trend might reflect a nationwide pattern rather than something specific to CFS.

E2 ModerateCohortPEM unclearLongitudinal

[Chronic fatigue syndrome].

Fucíková, T, Petanová, J·Vnitrni lekarstvi·1993

Researchers followed 52 ME/CFS patients for 1 to 14 years to see how they progressed over time. About 20% recovered completely, about 32% improved significantly, and about 15% developed thyroiditis (thyroid inflammation). The treatments used were mainly immune-modulating drugs chosen based on each patient's individual immune test results, though the benefits were only partial.

E2 ModerateCohortPEM unclearCross-Sectional

Lymphocyte phenotype and function in the chronic fatigue syndrome.

Straus, S E, Fritz, S, Dale, J K et al.·Journal of clinical immunology·1993

This 1993 study compared immune cells from 18 ME/CFS patients, 10 chronically fatigued patients who did not fully meet diagnostic criteria, and 17 healthy controls. Researchers observed that ME/CFS patients had lower percentages of a type of immune cell called CD4 T cells, and their immune cells showed reduced ability to respond to certain stimuli compared to healthy controls. However, this is a single cross-sectional study from over 30 years ago, and the findings have not yet been replicated in larger, more recent cohorts.

E2 ModerateCohortPEM not requiredCase-Control

Human herpesvirus 6 and chronic fatigue syndrome.

Eymard, D, Lebel, F, Miller, M et al.·The Canadian journal of infectious diseases = Journal canadien des maladies infectieuses·1993

This study compared antibody levels against human herpesvirus 6 (HHV-6) in two groups: people with ME/CFS and people with chronic fatigue who didn't meet the official ME/CFS diagnosis. Researchers found that people with ME/CFS had significantly higher antibody levels against HHV-6, suggesting the virus might play a role in the condition. The study also found that sore throat, headache, and recurrent fatigue were more common in the ME/CFS group.

E2 ModerateCohortPEM not requiredCross-Sectional

Studies on the relationship between chronic fatigue syndrome and Epstein-Barr virus in Japan.

Kawai, K, Kawai, A·Internal medicine (Tokyo, Japan)·1992

This study examined whether Epstein-Barr virus (EBV), a common virus that causes infectious mononucleosis, might be connected to chronic fatigue syndrome (CFS). Researchers tested 22 patients with long-lasting fatigue and found that those with definite CFS had higher levels of certain EBV antibodies compared to patients with milder symptoms and healthy controls. The study suggests a possible link between EBV activation and the severity of fatigue experienced.

E2 ModerateCohortPEM unclearObservational

Does chronic fatigue syndrome predispose to non-Hodgkin's lymphoma?

Levine, P H, Peterson, D, McNamee, F L et al.·Cancer research·1992

Some people with ME/CFS have reported concerns about developing lymphoma (a type of blood cancer). This study looked at cancer rates in Nevada before and after documented ME/CFS outbreaks in the mid-1980s to see if there was an increase in non-Hodgkin's lymphoma cases. The researchers found that cancer rates followed the same patterns as the rest of the country, with no unusual spike linked to ME/CFS.

E2 ModerateCohortPEM not requiredObservational

[Allergy among Japanese patients with chronic fatigue syndrome].

Matsumoto, Y, Ninomiya, S·Arerugi = [Allergy]·1992

This study looked at allergies in 18 Japanese patients with ME/CFS and found that 78% had allergies either before or after developing ME/CFS. Most allergies involved skin reactions or drug allergies. Interestingly, allergies that existed before ME/CFS often improved once the illness developed, but ME/CFS symptoms got worse when allergies were present.

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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.