ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

161–180 of 1,205 studies

Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome.

Hickie, I, Lloyd, A, Wakefield, D·The Australian and New Zealand journal of psychiatry·1992

This study examined whether depression and immune system problems in ME/CFS patients are connected. Researchers gave 33 patients with ME/CFS either a high-dose immune treatment or placebo and tracked changes in both mood and immune markers. Patients who received the real treatment showed that when their immune systems improved, their depression symptoms also improved together, suggesting these problems may be linked to the same underlying cause rather than one causing the other.

Immune System

E1 ReplicatedTrialPEM not requiredRCT

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome.

Peterson, P K, Shepard, J, Macres, M et al.·The American journal of medicine·1990

Researchers tested whether a blood product called intravenous immunoglobulin G (IV IgG) could help people with ME/CFS by giving it to 28 patients every month for 6 months. Although some patients had low levels of this protein at the start, IV IgG did not improve fatigue, daily functioning, or overall health compared to placebo, even though the treatment restored protein levels to normal.

Immune System

E1 ReplicatedTrialPEM not requiredRCT

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.

Lloyd, A, Hickie, I, Wakefield, D et al.·The American journal of medicine·1990

This study tested whether a high-dose immune protein treatment (intravenous immunoglobulin) could help people with ME/CFS. Researchers gave 49 patients either the treatment or placebo and measured changes in fatigue, mood, physical function, and immune markers. More people who received the treatment reported significant improvement and returned to work and activities compared to those who received placebo, suggesting immune system problems may play a role in ME/CFS.

Immune System

E2 ModerateCohortPEM unclearCross-Sectional

Elevated serum levels of interleukin-11 and matrix metalloproteinase-9 in myalgic encephalomyelitis/chronic fatigue syndrome.

Chinnappan, Baskaran, Kempuraj, Duraisamy, Aenlle, Kristina K et al.·Frontiers in immunology·2026

Researchers measured two immune proteins (IL-11 and MMP-9) in the blood of 40 ME/CFS patients and compared them to healthy controls, finding higher levels in the ME/CFS group. In the laboratory, they also showed that immune cells called mast cells release MMP-9 when exposed to a protein from Epstein-Barr virus. These are preliminary observations in one study that suggest these proteins may be associated with ME/CFS, but this does not yet establish their role in the disease.

NeuroinflammationBiomarkersImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Involvement of autoantibodies against G protein-coupled receptors in post-COVID condition and Chronic Fatigue Syndrome.

Azcue, N, Prada, A, Del Pino, R et al.·Scientific reports·2026

Researchers compared immune markers called autoantibodies in people with post-COVID condition, ME/CFS, and healthy controls. They found that people with ME/CFS had higher levels of antibodies against certain nerve receptors (β2 adrenergic), and these antibodies were associated with autonomic nervous system problems and memory changes. However, this is a single cross-sectional study, and autoimmunity remains one of several proposed mechanisms—it is not yet clear whether these antibodies are a cause or a consequence of ME/CFS.

BiomarkersAutonomic Nervous SystemImmune SystemCognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Epigenome-wide profiling identifies distinct DNA methylation architecture underlying ME/CFS and fibromyalgia symptom burden.

Polli, Andrea, Hendrix, Jolien, Wyns, Arne et al.·Journal of translational medicine·2026

Researchers compared blood cell DNA methylation (a chemical tag that regulates gene activity) in 71 people with ME/CFS, 44 with fibromyalgia, and 73 healthy controls. They found two distinct methylation patterns: one associated mainly with post-exertional malaise and cognitive symptoms in ME/CFS, and another associated with broader pain and sleep symptoms in both patient groups. This is one study in early-stage research; the findings have not yet been replicated in independent groups, and it remains unclear whether these methylation patterns could be used clinically to diagnose or monitor these conditions.

NeuroinflammationPain and SensitizationBiomarkersSleep

E2 ModerateCohortPEM not requiredCross-Sectional

Persistent fatigue in long-COVID is not associated with peripheral inflammatory or cellular stress biomarkers: A cross-sectional controlled study.

Omdal, Roald, Lenning, Ole Bernt, Jonsson, Grete et al.·Brain, behavior, & immunity - health·2026

A study of 48 people with long-COVID and 48 recovered controls found that fatigue was much more severe in the long-COVID group, but common blood markers of inflammation and cellular stress did not differ between the groups. This suggests that the fatigue in long-COVID may not be driven by the types of inflammation typically measured in blood tests, though the researchers note their findings are preliminary and limited to the biomarkers they tested.

NeuroinflammationBiomarkersImmune SystemLong COVID Overlap

E2 ModerateCohortPEM unclearCase-Control

Urinary Peptidomic Profiling In Post-Acute Sequelae of SARS-CoV-2 Infection: A Case-Control Study.

Gülmez, Dilara, Siwy, Justyna, Kurz, Katharina et al.·Proteomics·2026

Researchers found a simple urine test that can accurately identify people with long COVID (PASC) by measuring tiny protein fragments in the urine. The test correctly identified long COVID patients 96% of the time compared to healthy people and those with ME/CFS. The urine signatures suggest that long COVID involves ongoing inflammation and changes in how the body breaks down and rebuilds connective tissue.

BiomarkersImmune System

E2 ModerateCohortPEM not requiredObservational

Shared genetic risk between functional somatic syndromes, internalizing disorders, and immune-mediated diseases: a twin-sibling study.

Steen, Olivier D, Ohlsson, Henrik, van Ockenburg, Sonja L et al.·Brain, behavior, and immunity·2026

A large Swedish study examined whether functional somatic syndromes (including ME/CFS, fibromyalgia, and IBS) and depression/anxiety share genetic risk factors with immune-mediated diseases. Researchers observed that fibromyalgia showed the strongest shared genetic risk with immune diseases, while ME/CFS showed more modest genetic overlap. The findings are preliminary and do not explain why these conditions cluster together, only that genetic factors may contribute to some shared risk.

BiomarkersImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights.

Hoel, August, Hoel, Fredrik, Dyrstad, Sissel Elisabeth et al.·Cell reports. Medicine·2026

Researchers analyzed thousands of proteins in the blood of ME/CFS patients and compared them to healthy people. They found significant differences in protein patterns, including too much of certain immune-related proteins and too little of proteins normally made by muscles. These differences might help explain why ME/CFS causes such severe exhaustion and could eventually lead to new ways to diagnose or treat the condition.

BiomarkersImmune System

E2 ModerateCohortPEM unclearLongitudinal

Chronic Reactivation of Persistent Human Herpesviruses EBV, HHV-6 and VZV and Heightened Anti-dUTPase IgG Antibodies Are a Recurrent Hallmark in Post-Infectious ME/CFS and is Associated With Fatigue.

Palomo, Irene Mena, Cox, Brandon, Williams, Marshall V et al.·Journal of medical virology·2026

This study found that people with ME/CFS have higher levels of immune responses to three common viruses (EBV, HHV-6, and VZV) compared to healthy people. About 72% of ME/CFS patients showed antibodies to multiple viruses at the same time, versus only 31% of healthy controls. The antibody levels were higher in patients with moderate to severe fatigue, suggesting a possible connection between these viral reactivations and symptom severity.

BiomarkersImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Exploring differences in protein cargo of extracellular vesicles from ME/CFS patient plasma compared to healthy controls.

Rydland, Anne, Yran, Elena Støvring, Nyman, Tuula A et al.·Biochemistry and biophysics reports·2026

Researchers compared tiny particles called extracellular vesicles (EVs) in the blood of 49 ME/CFS patients and 50 healthy controls. They found that ME/CFS patients had higher concentrations of these particles, and 11 proteins inside them were observed at different levels in ME/CFS compared to controls—though these differences did not remain statistically significant after accounting for multiple comparisons. The study is exploratory and the authors note that further investigation is needed to understand whether these EV changes are relevant to ME/CFS.

BiomarkersImmune System

E2 ModerateCohortPEM unclearObservational

Exploratory clinical and immunological changes following Tixagevimab/Cilgavimab administration in immunodeficient patients with SARS-CoV-2-associated ME/CFS and persistent circulating spike protein.

Seidel, Maximilian, Anft, Moritz, Wiemers, Lea et al.·Immunology letters·2026

Researchers gave a monoclonal antibody treatment (Tixagevimab/Cilgavimab) to nine immunodeficient patients with long COVID and ME/CFS-like symptoms who had detectable coronavirus spike protein in their blood. After 30 days, one immune marker (β1-adrenergic receptor autoantibody) showed a modest decrease, but spike protein levels and symptom outcomes did not change significantly as a group. These are very preliminary findings from a small study without a control group, and the authors emphasise that efficacy remains uncertain.

BiomarkersInterventionsAutonomic Nervous SystemImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Sex- and menopause-related differences in immune and gastrointestinal symptom architecture in ME/CFS: evidence from factor analysis and structural equation modeling.

Habermann-Horstmeier, Lotte, Horstmeier, Lukas M·Journal of translational medicine·2026

This study examined how immune and gut symptoms are organized differently in women and men with ME/CFS, and whether menopause affects these patterns. Researchers analyzed data from 748 people with ME/CFS and observed that women tend to have two somewhat separate symptom clusters (immune-related and gut-related), while men showed these symptoms more integrated together. Among women, flu-like symptoms were reported more frequently before menopause than after, while gut symptoms remained stable across menopause. These are early findings from a single cross-sectional analysis and require confirmation in future studies.

Endocrine DisruptionGut MicrobiomeAutonomic Nervous SystemImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Overlapping Clinical Presentation of Long COVID and Postacute COVID-19 Vaccination Syndrome: Phenotypes, Severity, and Biomarkers.

Purpura, Lawrence, Heisler, Thomas, Palmer, Steven et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·2026

This study compared three groups of people dealing with long-term effects from COVID-19: those with long COVID and ME/CFS, those with long COVID without ME/CFS, and those with symptoms after COVID-19 vaccination. While all three groups shared common symptoms like fatigue, the ME/CFS group experienced more widespread symptoms across their body. Interestingly, people in the vaccination-related group had higher rates of unusual symptoms like nerve pain and rashes, and their blood tests showed different patterns of autoimmune markers—substances that suggest the immune system may be attacking the body's own tissues.

Immune System

E2 ModerateCohortPEM unclearCase-Control

Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a case-control study.

Missailidis, Daniel, Armstrong, Christopher W, Anderson, Dovile et al.·Journal of translational medicine·2026

Researchers studied immune cells from people with ME/CFS and found that these cells accumulate abnormal amounts of fats (lipids) compared to healthy controls. The cells also show changes in how they process and use these fats for energy. This discovery suggests that problems with how the body handles fats might be part of what makes ME/CFS different at the cellular level.

Immune System

E2 ModerateCohortPEM unclearCross-Sectional

Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Ikeda, Gentaro, Koike-Ieki, Mariko, Inoue, Hiroyuki et al.·Open forum infectious diseases·2026

Researchers analyzed tiny cell particles called extracellular vesicles in blood samples from people with Long COVID, ME/CFS, and healthy controls. They observed that both Long COVID and ME/CFS groups had elevated levels of certain immune cell-derived particles and alterations in mitochondrial (energy-producing) markers within B cells and other immune cells, though the findings were not identical between groups. These preliminary results suggest there may be shared immune and metabolic changes in these conditions, but the meaning of these changes for patient health remains unclear and needs further study.

BiomarkersEnergy MetabolismImmune SystemLong COVID Overlap

E2 ModerateCohortPEM unclearCross-Sectional

Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID.

Petrov, Steliyan, Bozhkova, Martina, Ivanovska, Mariya et al.·International journal of molecular sciences·2026

Researchers compared immune cell patterns in 103 people with ME/CFS, 63 with long COVID, and 41 healthy controls using blood tests. They observed that ME/CFS and long COVID show different patterns of immune cell activity—long COVID appeared to show persistent immune activation, while ME/CFS appeared associated with reduced immune signalling. These are early findings from one study and do not yet tell us what causes either condition or how to treat it.

BiomarkersDiagnosticsImmune SystemLong COVID Overlap

E2 ModerateCohortPEM unclearLongitudinal

Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

Jones, Ansley E, Khan, Zain, McGroder, Claire F et al.·Critical care explorations·2026

This study followed people who were hospitalized with severe COVID-19 for 3 years after they left the hospital. About one-quarter of them continued to experience long COVID symptoms like fatigue, brain fog, and difficulty with physical activity. Surprisingly, when researchers measured inflammation and blood vessel markers in their blood, these markers were not elevated and did not explain why some people had ongoing symptoms.

BiomarkersImmune SystemPost-Exertional Malaise

E2 ModerateCohortPEM unclearObservational

A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis - chronic fatigue syndrome.

Hirsch, Annemarie G, Justice, Anne E, Poissant, Amy et al.·BMC infectious diseases·2025

Researchers studied the genes of people who had Lyme disease to understand why some develop lasting symptoms even after treatment. They found two genetic regions that might be involved in persistent Lyme disease symptoms, with one linked to a protein called MARC2 that affects immune function. When they checked whether these same genetic changes appeared in people with fibromyalgia or ME/CFS, they did not find the same patterns, suggesting these conditions may have different genetic roots.

Immune System

← Previous Next 20 studies →

Or browse by topic

PEM Immune Neuro Metabolic Biomarkers Severe ME Long COVID Cognitive

Evidence Atlas

Evidence browser

Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome.

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome.

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.

Elevated serum levels of interleukin-11 and matrix metalloproteinase-9 in myalgic encephalomyelitis/chronic fatigue syndrome.

Involvement of autoantibodies against G protein-coupled receptors in post-COVID condition and Chronic Fatigue Syndrome.

Epigenome-wide profiling identifies distinct DNA methylation architecture underlying ME/CFS and fibromyalgia symptom burden.

Persistent fatigue in long-COVID is not associated with peripheral inflammatory or cellular stress biomarkers: A cross-sectional controlled study.

Urinary Peptidomic Profiling In Post-Acute Sequelae of SARS-CoV-2 Infection: A Case-Control Study.

Shared genetic risk between functional somatic syndromes, internalizing disorders, and immune-mediated diseases: a twin-sibling study.

Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights.

Chronic Reactivation of Persistent Human Herpesviruses EBV, HHV-6 and VZV and Heightened Anti-dUTPase IgG Antibodies Are a Recurrent Hallmark in Post-Infectious ME/CFS and is Associated With Fatigue.

Exploring differences in protein cargo of extracellular vesicles from ME/CFS patient plasma compared to healthy controls.

Exploratory clinical and immunological changes following Tixagevimab/Cilgavimab administration in immunodeficient patients with SARS-CoV-2-associated ME/CFS and persistent circulating spike protein.

Sex- and menopause-related differences in immune and gastrointestinal symptom architecture in ME/CFS: evidence from factor analysis and structural equation modeling.

Overlapping Clinical Presentation of Long COVID and Postacute COVID-19 Vaccination Syndrome: Phenotypes, Severity, and Biomarkers.

Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a case-control study.

Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID.

Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis - chronic fatigue syndrome.

Curated Collections

Neuroinflammation Evidence

Metabolism & Mitochondria

Biomarkers

PEM-Specific Research