Evidence browser

NeuroinflammationImmune System

In Schizophrenia, Chronic Fatigue Syndrome- and Fibromyalgia-Like Symptoms are Driven by Breakdown of the Paracellular Pathway with Increased Zonulin and Immune Activation-Associated Neurotoxicity.

Maes, Michael, Andrés-Rodríguez, Laura, Vojdani, Aristo et al.·CNS & neurological disorders drug targets·2023

This study looked at people with schizophrenia who also experience fatigue and pain symptoms similar to ME/CFS and fibromyalgia. Researchers found that these symptoms may be caused by a breakdown in the intestinal barrier (the paracellular pathway), which allows harmful substances into the bloodstream and triggers immune system activation. This immune activation then produces neurotoxic byproducts that may cause the fatigue and pain symptoms.

Influence of Chronic Fatigue Syndrome Codiagnosis on the Relationship between Perceived and Objective Psychoneuro-Immunoendocrine Disorders in Women with Fibromyalgia.

Otero, Eduardo, Gálvez, Isabel, Ortega, Eduardo et al.·Biomedicines·2023

This study compared women with fibromyalgia (FM), some of whom also had been diagnosed with chronic fatigue syndrome (CFS), to healthy women. Researchers measured both what patients reported feeling (like stress and pain levels) and actual biological markers in their blood (like stress hormones and immune chemicals). They found that FM patients generally felt worse than healthy women, and their blood work matched this—showing higher stress hormones and lower mood-boosting chemicals. Interestingly, FM patients who also had a CFS diagnosis showed different blood markers than those with FM alone, suggesting these two conditions may overlap in ways that current diagnosis methods don't catch.

E2 ModerateCohortPEM not requiredObservational

Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls.

Giloteaux, Ludovic, Li, Jiayin, Hornig, Mady et al.·Journal of translational medicine·2023

Researchers studied tiny particles called extracellular vesicles found in the blood of ME/CFS patients and compared them to healthy controls. They found that ME/CFS patients had more of these particles and they contained different levels of immune chemicals, particularly one called IL2. Using computer algorithms to analyze 20 different blood proteins, they could correctly identify ME/CFS patients about 86% of the time, suggesting that blood tests might one day help diagnose this condition.

Cytokine network analysis in a community-based pediatric sample of patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Jason, Leonard A, Gaglio, Caroline L, Furst, Jacob et al.·Chronic illness·2023

Researchers studied immune system chemicals called cytokines in children and teens with ME/CFS by comparing blood samples from sick patients and healthy controls. They found that children with ME/CFS had different patterns of these immune chemicals compared to healthy kids, with certain inflammatory markers being more active. This suggests ME/CFS involves real biological changes in how the immune system works, particularly in severe cases.

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome.

Wang, Zheng, Waldman, Michelle F, Basavanhally, Tara J et al.·Journal of translational medicine·2022

Researchers tested blood samples from 166 ME/CFS patients and 83 healthy people to look for immune system clues that might explain the disease. They found that six specific genes related to immune function were more active in patients with severe, bedridden ME/CFS compared to those with milder disease. The study suggests these genes could potentially be used as biomarkers to identify how severe someone's ME/CFS is and might point toward new treatments.

Immune SystemPost-Exertional Malaise

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Syndrome: A Common Neuroimmune Ground?

Ryabkova, Varvara A, Gavrilova, Natalia Y, Fedotkina, Tamara V et al.·Diagnostics (Basel, Switzerland)·2022

This Russian study looked at 56 people with ME/CFS and 14 people with post-COVID syndrome to understand how their bodies function differently. The researchers found that both groups had similar patterns of immune system problems, heart rate changes when standing up, and reduced blood flow in small vessels. Importantly, fatigue severity was linked to many other ME/CFS symptoms but not to anxiety or depression.

No difference in serum levels of B-cell activating receptor and antibodies against cytolethal distending toxin B and flagellin in post-infectious irritable bowel syndrome and chronic fatigue syndrome after Giardia infection.

Hanevik, Kurt, Saghaug, Christina, Aaland, Maren et al.·JGH open : an open access journal of gastroenterology and hepatology·2022

This study looked for three potential biological markers (BAFF, anti-CdtB, and anti-flagellin antibodies) in the blood of people who developed ME/CFS and/or IBS after a Giardia infection. Researchers compared these markers in patients to healthy controls but found no significant differences between the groups. The findings suggest these three markers are not useful for diagnosing ME/CFS or IBS.

E2 ModerateCohortPEM requiredObservational

A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity.

Kedor, Claudia, Freitag, Helma, Meyer-Arndt, Lil et al.·Nature communications·2022

This study followed 42 people with long-lasting fatigue after COVID-19 infection for six months and compared them to people with similar chronic fatigue from other causes. Most participants experienced moderate to severe fatigue that interfered with daily life. The researchers found that many of these post-COVID patients had reduced hand grip strength and blood markers suggesting possible inflammation and poor blood flow, which may help explain why their bodies struggle to recover.

Immune SystemPost-Exertional Malaise

E2 ModerateCohortPEM unclearObservational

Predictors for Developing Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Following Infectious Mononucleosis.

Jason, Leonard A, Cotler, Joseph, Islam, Mohammed F et al.·Journal of rehabilitation therapy·2022

This study followed 238 college students who developed infectious mononucleosis to see who would recover and who would develop ME/CFS. Researchers found that students who had stomach problems (pain, bloating, irritable bowel) before getting sick, combined with certain low immune markers and severe digestive symptoms when they got mononucleosis, had about an 80% chance of developing severe ME/CFS that lasted six months. This suggests that pre-existing gut problems and immune differences may help predict who is at highest risk.

Systemic antibody responses against human microbiota flagellins are overrepresented in chronic fatigue syndrome patients.

Vogl, Thomas, Kalka, Iris N, Klompus, Shelley et al.·Science advances·2022

Researchers found that people with severe ME/CFS have different immune responses against bacteria in their gut compared to healthy people. Specifically, their blood contains more antibodies (immune proteins) that target flagella, which are whip-like structures used by certain gut bacteria to move. This immune signature was so distinctive that a computer algorithm could use it to help identify ME/CFS patients.

E2 ModerateCohortPEM unclearObservational

Pre-illness data reveals differences in multiple metabolites and metabolic pathways in those who do and do not recover from infectious mononucleosis.

Jason, Leonard A, Conroy, Karl E, Furst, Jacob et al.·Molecular omics·2022

This study looked at blood samples taken from college students before they got sick to see if certain chemical markers could predict who would recover from mononucleosis and who would develop ME/CFS instead. Researchers found that people who later developed ME/CFS had different levels of certain chemicals in their blood before they even got sick, particularly those involved in energy production and immune function. Using a computer model based on these chemical differences, they could correctly predict with 97% accuracy which people would recover and which would develop ME/CFS.

Intersections between pneumonia, lowered oxygen saturation percentage and immune activation mediate depression, anxiety, and chronic fatigue syndrome-like symptoms due to COVID-19: A nomothetic network approach.

Al-Jassas, Hawraa Kadhem, Al-Hakeim, Hussein Kadhem, Maes, Michael·Journal of affective disorders·2022

This study examined 60 COVID-19 patients and 30 healthy controls to understand why some people develop depression, anxiety, and fatigue-like symptoms after COVID-19 infection. The researchers found that lung damage (seen on CT scans), low oxygen levels, and an overactive immune response are connected to these mental health and fatigue symptoms. Essentially, the physical damage to the lungs may trigger immune system activation, which then leads to depression, anxiety, and fatigue.

Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis.

Smesam, Hasan Najah, Qazmooz, Hasan Abbas, Khayoon, Sinan Qayes et al.·Journal of personalized medicine·2022

This study looked at 118 people with rheumatoid arthritis (RA, an autoimmune disease affecting joints) and 50 healthy people to understand why RA patients often experience depression, anxiety, and fatigue. Researchers measured immune system markers and psychological symptoms, finding that about 70% of these mental and fatigue symptoms could be explained by the same immune system problems that cause RA itself.

E2 ModerateCohortPEM unclearCase-Control

Genetic risk factors for ME/CFS identified using combinatorial analysis.

Das, Sayoni, Taylor, Krystyna, Kozubek, James et al.·Journal of translational medicine·2022

Researchers identified 199 genetic variations in 14 genes that are associated with ME/CFS by analyzing genetic data from thousands of people in UK Biobank. These genetic variations work together in groups to influence ME/CFS risk and were found in 91% of people with ME/CFS in the study. The identified genes are involved in processes the body uses to handle stress, infection, energy production in cells, sleep, and immune function—all areas that scientists think may go wrong in ME/CFS.

Immune SystemPost-Exertional Malaise

E2 ModerateCohortPEM not requiredObservational

HERV-W ENV antigenemia and correlation of increased anti-SARS-CoV-2 immunoglobulin levels with post-COVID-19 symptoms.

Giménez-Orenga, Karen, Pierquin, Justine, Brunel, Joanna et al.·Frontiers in immunology·2022

This study found that a dormant virus-like element called HERV-W, which exists naturally in our DNA, may reactivate and remain active long after COVID-19 infection has cleared in people with long COVID. The researchers also discovered that people with higher levels of certain immune proteins (antibodies) against SARS-CoV-2, especially IgE antibodies, tended to have worse physical function. These findings suggest that HERV-W activation and lingering antibody responses might help explain why some people develop long-lasting COVID symptoms.

NeuroinflammationImmune System

Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways.

Maes, Michael, Al-Rubaye, Haneen Tahseen, Almulla, Abbas F et al.·International journal of environmental research and public health·2022

This study found that Long COVID patients have significantly lower quality of life compared to healthy people, and this decline is mostly explained by three factors: mood and pain-related symptoms (like depression, anxiety, and fatigue), signs of ongoing inflammation in the body, and problems with how the body processes calcium. The severity of the initial infection—measured by high fever and low oxygen levels—also plays a role by triggering these inflammatory and immune problems that persist afterward.

E2 ModerateCohortPEM not requiredLongitudinal

How mycobacterium tuberculosis infection could lead to the increasing risks of chronic fatigue syndrome and the potential immunological effects: a population-based retrospective cohort study.

Yang, Tse-Yen, Lin, Cheng-Li, Yao, Wei-Cheng et al.·Journal of translational medicine·2022

This study found that people who have had a tuberculosis infection are about 23% more likely to develop ME/CFS than people who have never had tuberculosis. Researchers in Taiwan tracked over 38,000 people for about 10 years and noticed that tuberculosis and ME/CFS share similar symptoms and immune system patterns. The link was especially strong in men and in people aged 65 and older.

Comparative Analysis of Extracellular Vesicles in Patients with Severe and Mild Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Bonilla, Hector, Hampton, Dylan, Marques de Menezes, Erika G et al.·Frontiers in immunology·2022

Researchers looked for tiny particles called extracellular vesicles in the blood of people with ME/CFS to see if they could help diagnose or understand the disease. They found that people with severe ME/CFS had higher levels of certain vesicles that come from B cells (immune cells) and platelets (blood clotting cells) compared to healthy people. While these differences were promising, they weren't strong enough to confirm they're reliable markers yet.

Survey of Anti-Pathogen Antibody Levels in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

O'Neal, Adam J, Glass, Katherine A, Emig, Christopher J et al.·Proteomes·2022

Researchers tested blood samples from ME/CFS patients to look for antibodies against 122 different germs that might trigger the illness. They compared the results to healthy people of similar age, sex, and weight. While they found differences in how men and women with ME/CFS respond to infections, they couldn't identify one specific germ as the culprit.

Chronic Fatigue Exhibits Heterogeneous Autoimmunity Characteristics Which Reflect Etiology.

Danilenko, Olga V, Gavrilova, Natalia Y, Churilov, Leonid P·Pathophysiology : the official journal of the International Society for Pathophysiology·2022

This study found that ME/CFS patients have unusual immune system patterns—specifically, their bodies produce antibodies (immune proteins) that attack their own nervous system tissues. The researchers divided ME/CFS patients into three groups based on cause (viral infection, stress, or unknown origin) and found that different groups had different patterns of these self-attacking antibodies. Importantly, all ME/CFS patients showed elevated levels of antibodies against brain and nerve proteins, which could explain why the illness affects multiple body systems.