Evidence browser

Association analysis between symptomology and herpesvirus IgG antibody concentrations in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis.

Domingues, Tiago Dias, Malato, João, Grabowska, Anna D et al.·Heliyon·2023

This study looked at whether past infections with common herpesviruses (like the virus that causes cold sores or chickenpox) are connected to specific symptoms in ME/CFS patients. Researchers tested blood samples from 222 ME/CFS patients and 46 MS patients to measure antibodies against six different herpesviruses, then compared these results to reported symptoms. They found some connections—particularly between a virus called HSV1 and brain fog in ME/CFS patients—but overall, herpesvirus antibodies explained symptoms better in MS patients than in ME/CFS patients.

Mood Symptoms and Chronic Fatigue Syndrome Due to Relapsing-Remitting Multiple Sclerosis Are Associated with Immune Activation and Aberrations in the Erythron.

Almulla, Abbas F, Abdul Jaleel, Al-Karrar Kais, Abo Algon, Ali Abbas et al.·Brain sciences·2023

This study looked at 63 people with multiple sclerosis (MS) and 30 healthy controls to understand why MS patients experience chronic fatigue, depression, and anxiety. Researchers found that about half of the MS patients had signs of immune system overactivation and problems with red blood cell levels. These immune and blood abnormalities were linked to their fatigue and mood symptoms.

Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa.

Hannestad, Ulf, Apostolou, Eirini, Sjögren, Per et al.·Frontiers in medicine·2023

This study found that people with ME/CFS who caught COVID-19 showed signs of a dormant virus (adenovirus) waking up in their mouth and throat. The researchers compared saliva samples from ME/CFS patients and healthy people, and only the ME/CFS patients showed this reactivation after COVID-19 infection. This suggests that ME/CFS patients may have a weakened immune system that cannot keep these latent viruses under control when faced with a new infection like COVID-19.

E2 ModerateCohortPEM unclearObservational

Low-dose naltrexone use for the management of post-acute sequelae of COVID-19.

Bonilla, Hector, Tian, Lu, Marconi, Vincent C et al.·International immunopharmacology·2023

This study looked at whether a medication called low-dose naltrexone (LDN) might help people with long COVID symptoms. Researchers reviewed 59 patients who took LDN and found that those who used it reported fewer overall symptoms, felt less fatigue and brain fog, experienced better sleep, and had improved ability to do daily activities. While these early results are encouraging, the study was not designed like a typical clinical trial, so more rigorous testing is needed to know if LDN truly works.

Immune SystemNeuroinflammation

Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro-Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection.

Al-Hakeim, Hussein Kadhem, Al-Rubaye, Haneen Tahseen, Almulla, Abbas F et al.·Journal of clinical medicine·2023

This study examined whether severe COVID-19 infection—particularly high fever and low oxygen levels—can trigger lasting fatigue, depression, and anxiety through inflammation and oxidative stress in the body. Researchers compared 86 long COVID patients with 39 healthy controls and found that about one-third of long COVID patients had very high signs of immune activation and cellular damage. The study suggests that the severity of initial COVID infection may predict who develops long-term symptoms through measurable changes in inflammatory markers.

Distinguishing features of long COVID identified through immune profiling.

Klein, Jon, Wood, Jamie, Jaycox, Jillian R et al.·Nature·2023

Researchers studied 275 people with and without long COVID to understand what happens in the immune system. They found that people with long COVID have different patterns of immune cells and antibodies, including stronger responses to past viral infections like Epstein-Barr virus, and lower levels of the stress hormone cortisol. Using computer analysis, they identified specific immune markers that could help identify who has long COVID.

E2 ModerateCohortPEM requiredCross-Sectional

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia: PR3-versus MPO-ANCA-associated vasculitis, an exploratory cross-sectional study.

van Eeden, Charmaine, Mohazab, Naima, Redmond, Desiree et al.·Lancet regional health. Americas·2023

This study looked at fatigue in people with ANCA-vasculitis (a type of blood vessel inflammation) and found that over half met the diagnostic criteria for ME/CFS. The researchers discovered that the type of vasculitis matters: people with MPO-ANCA had fatigue patterns more similar to fibromyalgia, while those with PR3-ANCA had fatigue linked to inflammation markers. This suggests different types of vasculitis may cause fatigue through different biological mechanisms.

E2 ModerateCohortPEM unclearObservational

Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infection.

Guo, Lihui, Appelman, Brent, Mooij-Kalverda, Kirsten et al.·EBioMedicine·2023

This study found that people with long-COVID have persistent activity of an enzyme called IDO2 in their blood cells and brain tissue, months or years after initial infection. This enzyme breaks down tryptophan (an amino acid) into other compounds that may trigger cellular stress and energy problems. The researchers also discovered that blocking a specific receptor (called AHR) could stop this process in laboratory tests, suggesting a potential treatment target.

Energy MetabolismImmune SystemPost-Exertional Malaise

Immune SystemNeuroinflammation

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.

E2 ModerateCohortPEM requiredLongitudinal

Long-term symptom severity and clinical biomarkers in post-COVID-19/chronic fatigue syndrome: results from a prospective observational cohort.

Legler, Franziska, Meyer-Arndt, Lil, Mödl, Lukas et al.·EClinicalMedicine·2023

This study followed 106 people with long-term fatigue after COVID-19 for up to 20 months to see how they recovered over time. Researchers found that some patients met the diagnostic criteria for ME/CFS and had persistent, severe symptoms including fatigue and post-exertional malaise (worsening after activity), while others improved more substantially. Lower muscle strength at the start of illness was linked to ongoing symptoms, especially in those with ME/CFS.

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.

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation.

Szewczykowski, Charlotte, Mardin, Christian, Lucio, Marianna et al.·International journal of molecular sciences·2022

Some people with Long COVID have abnormal immune proteins called autoantibodies that attack blood vessel control systems in their bodies. This study found that patients with these specific autoantibodies had reduced blood flow in the tiny vessels at the back of the eye, which may reflect similar problems throughout their whole body and could explain some of their symptoms.

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.

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.

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.

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.

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 unclearCase-Control

Revisiting IgG Antibody Reactivity to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Its Potential Application to Disease Diagnosis.

Sepúlveda, Nuno, Malato, João, Sotzny, Franziska et al.·Frontiers in medicine·2022

This study looked at antibody responses to Epstein-Barr virus (EBV), a common virus linked to ME/CFS onset in some patients. Researchers analyzed blood samples from 92 ME/CFS patients and 50 healthy people, testing reactions to over 3,000 EBV proteins. They found that in patients whose ME/CFS started after a suspected EBV infection, two specific viral proteins triggered stronger antibody responses than in healthy controls. These antibody patterns could correctly identify about 83% of infected patients and 72% of healthy people, suggesting they might become useful diagnostic markers.

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.

Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome.

Apostolou, Eirini, Rizwan, Muhammad, Moustardas, Petros et al.·Frontiers in immunology·2022

This study found that people with ME/CFS have a different immune response to COVID-19 compared to healthy people, even when the COVID infection is mild. Specifically, the researchers discovered that after COVID-19, dormant viruses (like EBV and others) reactivate more strongly in people with ME/CFS, as shown by antibody patterns in saliva. This suggests that COVID-19 may trigger hidden virus reactivation that could contribute to fatigue symptoms in ME/CFS patients.