Evidence browser

BiomarkersDiagnosticsImmune SystemLong COVID Overlap

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.

BiomarkersAutonomic Nervous SystemImmune SystemCognitive Impairment

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.

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.

BiomarkersEnergy MetabolismImmune SystemLong COVID Overlap

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.

NeuroinflammationBiomarkersImmune System

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.

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 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.

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.

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.

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.

Mapping the complexity of ME/CFS: Evidence for abnormal energy metabolism, altered immune profile, and vascular dysfunction.

Heng, Benjamin, Gunasegaran, Bavani, Krishnamurthy, Shivani et al.·Cell reports. Medicine·2025

This study examined blood samples from ME/CFS patients and healthy people to understand what goes wrong in the body. Researchers found that immune cells in ME/CFS patients are struggling to make energy (ATP), the fuel that powers our cells. The immune system also showed signs of being immature or worn out, and blood proteins related to clotting and blood vessel problems were elevated, suggesting blood vessel dysfunction may contribute to ME/CFS symptoms.

An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques.

Germain, Arnaud, Jaycox, Jillian R, Emig, Christopher J et al.·International journal of molecular sciences·2025

This study looked for specific immune proteins called autoantibodies in the blood of ME/CFS patients to see if they might be causing the illness. Researchers tested over 7,500 different immune markers using advanced laboratory techniques in 172 people. Surprisingly, they did not find significant differences in autoantibodies between ME/CFS patients and healthy controls, though they did notice some subtle patterns between men and women with ME/CFS that warrant further investigation.

HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entity.

Giménez-Orenga, Karen, Martín-Martínez, Eva, Nathanson, Lubov et al.·eLife·2025

This study looked at special genetic materials called human endogenous retroviruses (HERVs) in the blood cells of women with ME/CFS, fibromyalgia, both conditions, or neither. The researchers found that the pattern of which HERVs were active could perfectly distinguish between these four groups—suggesting this could become a reliable blood test to diagnose these conditions. The study also found that ME/CFS patients had specific changes in immune cells that matched how severe their symptoms were.

E2 ModerateCohortPEM requiredCase-Control

Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch® 3-dimensional genomic regulatory immuno-genetic profiling.

Hunter, Ewan, Alshaker, Heba, Bundock, Oliver et al.·Journal of translational medicine·2025

Researchers developed a new blood test called EpiSwitch®CFS that may help diagnose ME/CFS by detecting specific patterns in how DNA is organized in blood cells. When tested on stored blood samples from 47 ME/CFS patients and 61 healthy people, the test correctly identified 92% of ME/CFS patients and correctly ruled out 98% of healthy controls. This could potentially help doctors diagnose ME/CFS more reliably, since there is currently no standard blood test for the condition.

NeuroinflammationBiomarkersImmune System

Circulating cell-free RNA signatures for the characterization and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome.

Gardella, Anne E, Eweis-LaBolle, Daniel, Loy, Conor J et al.·Proceedings of the National Academy of Sciences of the United States of America·2025

Researchers analyzed tiny pieces of RNA floating in the blood of people with ME/CFS and compared them to healthy people. They used a computer program to identify a pattern of these RNA pieces that could help diagnose ME/CFS with 77% accuracy. The study found that people with ME/CFS have different levels of immune cells releasing material into their blood, suggesting the immune system is behaving differently.

E2 ModerateCohortPEM not requiredObservational

Single-Center Study of Therapeutic Apheresis in 24 Male Patients from the MENA Region: Reduction of Lipids, Inflammatory Markers, Autoantibodies, and Implications for Fatigue, Genetics, and Aging.

Steenblock, Charlotte, Walther, Romy, Kok, Yannick et al.·Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme·2025

This study tested a blood-cleaning procedure called apheresis in 24 men from the Middle East and North Africa who had chronic fatigue and metabolic problems like diabetes or high cholesterol. The procedure removed harmful fats and immune molecules from their blood. After treatment, patients showed improvements in their blood work, with reduced inflammatory markers and autoantibodies that may contribute to fatigue.

E2 ModerateCohortPEM unclearObservational

Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study.

Steen, Olivier D, Bos, Martje, van Ockenburg, Sonja L et al.·BMC medicine·2025

This study found that ME/CFS, fibromyalgia, and irritable bowel syndrome tend to run in families alongside conditions like depression, anxiety, autoimmune diseases, and metabolic disorders. Researchers analyzed data from over 166,000 people in a Dutch population cohort to understand whether these conditions share common inherited risk factors. The findings suggest that the causes of functional disorders like ME/CFS may overlap with the causes of immune and metabolic diseases, which could point to new treatment approaches.

Immune SystemLong COVID Overlap

Comparable Immune Alterations and Inflammatory Signatures in ME/CFS and Long COVID.

Petrov, Steliyan, Bozhkova, Martina, Ivanovska, Mariya et al.·Biomedicines·2025

This study compared immune system markers in people with ME/CFS and Long COVID to those of healthy individuals. Both patient groups showed similar immune problems: lower levels of protective immune cells and higher levels of inflammatory substances in their blood. The findings suggest that ME/CFS and Long COVID may involve very similar underlying immune dysfunction.

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.