Evidence browser

Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study.

Domingo, Joan Carles, Battistini, Federica, Cordobilla, Begoña et al.·Journal of translational medicine·2024

This study compared blood markers and body responses between people with ME/CFS, people with long COVID, and healthy controls. Researchers found that people with ME/CFS had distinct patterns of inflammation and blood vessel dysfunction compared to long COVID patients, suggesting these are different conditions with different underlying problems. By measuring specific proteins in the blood and testing how the body responds to positional changes, researchers could tell the two patient groups apart.

BiomarkersImmune System

Energy MetabolismImmune System

Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome.

Saito, Suguru, Shahbaz, Shima, Luo, Xian et al.·Frontiers in immunology·2024

This study looked at blood samples from people with long COVID who have ME/CFS-like symptoms and compared them to people who recovered from COVID, people with acute COVID, and people who never had COVID. Researchers found that long COVID patients had unusual chemical patterns in their blood, higher levels of inflammation-promoting substances, and lower energy molecules (ATP). They also discovered that two specific chemicals (sarcosine and serine) were reduced in long COVID patients and connected to depression, anxiety, and brain fog.

E2 ModeratePEM unclearRegistry-Resource

Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS).

Mundorf, Anna Katharina, Semmler, Amelie, Heidecke, Harald et al.·Vaccines·2024

This study looked at 191 people who developed long-term illness after receiving a COVID-19 vaccine, a rare condition affecting about 2 in 10,000 vaccinated people. The most common symptoms were extreme tiredness and overall malaise (affecting over 80%), along with problems like nerve pain, heart issues, and cognitive difficulties. The researchers found that many of these patients meet the criteria for ME/CFS, though some appear to have a different condition entirely.

Long COVID diagnostic with differentiation from chronic lyme disease using machine learning and cytokine hubs.

Patterson, Bruce K, Guevara-Coto, Jose, Mora, Javier et al.·Scientific reports·2024

Researchers developed a computer-based test using blood measurements called cytokines to accurately identify long COVID (also called PASC) in patients. The test was able to correctly identify long COVID in 97% of cases and correctly rule it out in 90% of cases when tested on a new group of people. Importantly, the test could also distinguish long COVID from chronic Lyme disease, which can cause similar symptoms, helping doctors diagnose the right condition.

E2 ModerateMechanismPEM unclearMechanistic

Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery.

Nunes, Massimo, Vlok, Mare, Proal, Amy et al.·Cardiovascular diabetology·2024

Researchers analyzed blood proteins in 15 ME/CFS patients and 10 healthy controls to look for differences that might explain ME/CFS symptoms. They found that ME/CFS patients had abnormal levels of proteins involved in blood clotting, blood vessel function, and immune system regulation. These findings suggest that problems with blood clotting and blood vessel health may play a role in ME/CFS.

BiomarkersImmune System

Energy MetabolismImmune System

Untargeted Metabolomics and Quantitative Analysis of Tryptophan Metabolites in Myalgic Encephalomyelitis Patients and Healthy Volunteers: A Comparative Study Using High-Resolution Mass Spectrometry.

Abujrais, Sandy, Vallianatou, Theodosia, Bergquist, Jonas·ACS chemical neuroscience·2024

Researchers compared blood chemistry between 38 people with ME/CFS and 24 healthy people to understand what might be different in their bodies. They found several chemical imbalances, particularly in how the body processes tryptophan (an amino acid) and in pathways related to energy production and inflammation. These differences suggest that ME/CFS patients may experience unusual immune activity and stress damage to their cells.

In major dysmood disorder, physiosomatic, chronic fatigue and fibromyalgia symptoms are driven by immune activation and increased immune-associated neurotoxicity.

Maes, Michael, Almulla, Abbas F, Zhou, Bo et al.·Scientific reports·2024

This study found that people with severe depression often experience fatigue and pain symptoms similar to ME/CFS, and these symptoms are linked to overactive immune responses in the body. Researchers measured immune molecules in the blood of severely depressed patients and healthy controls, and discovered that specific immune markers—particularly IL-16 and IL-8—were associated with how severe the fatigue and physical symptoms were. The study suggests that difficult life experiences and traumatic childhood events may trigger these immune changes, leading to the physical symptoms that patients experience.

Exploring the role of galectin-9 and artemin as biomarkers in long COVID with chronic fatigue syndrome: links to inflammation and cognitive function.

Elahi, Shokrollah, Rezaeifar, Maryam, Osman, Mohammed et al.·Frontiers in immunology·2024

Researchers studied two proteins in the blood—galectin-9 and artemin—to see if they could help identify people with Long COVID who also have ME/CFS. They found that galectin-9 levels were higher in Long COVID patients and were linked to inflammation and thinking problems. These proteins may help doctors distinguish Long COVID with ME/CFS from people who recovered normally from COVID-19.

Gut MicrobiomeImmune System

Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn's disease and chronic fatigue syndrome.

Bourgonje, Arno R, Hörstke, Nicolai V, Fehringer, Michaela et al.·Microbiome·2024

This study looked at immune responses in ME/CFS and Crohn's disease patients by measuring antibodies against proteins from gut bacteria called flagellins. Researchers found that both patient groups had elevated antibodies against these bacterial proteins, but the pattern of where these antibodies attached differed between the two diseases. These antibody patterns could potentially help doctors diagnose ME/CFS and understand how the immune system may be responding abnormally to gut bacteria.

E2 ModerateCohortPEM requiredCross-Sectional

Immunological Patient Stratification in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Rohrhofer, Johanna, Hauser, Lisa, Lettenmaier, Lisa et al.·Journal of clinical medicine·2024

This study found that ME/CFS patients have different types of immune system problems. Researchers divided patients into two groups: those with weakened immune systems and those with normal immune systems. The two groups showed different patterns of illness—one group had low levels of a protective immune protein, while the other group had signs that their gut barrier was leaking. This suggests that ME/CFS may not be one disease but rather multiple conditions that need different treatment approaches.

E2 ModerateCohortPEM not requiredObservational

Naturally acquired adaptive immunity to Streptococcus pneumoniae is impaired in rheumatoid arthritis patients.

Ercoli, Giuseppe, Selway-Clarke, Hugh, Truijen, Dena et al.·Clinical & translational immunology·2024

This study compared how well people with rheumatoid arthritis (RA) and ME/CFS patients can fight off a common bacterial infection called Streptococcus pneumoniae. Researchers found that RA patients had weaker immune responses to this bacteria compared to ME/CFS patients, which may explain why RA patients get pneumonia more often. The study also looked at how a common RA treatment (rituximab, which depletes B cells) affected these immune responses.

IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry.

Fonseca, André, Szysz, Mateusz, Ly, Hoang Thien et al.·Medicina (Kaunas, Lithuania)·2024

Researchers examined immune responses (antibodies) against Epstein-Barr virus in ME/CFS patients to see if these could be used to diagnose the condition. They found that a specific set of 26 antibodies could reliably identify ME/CFS patients whose illness started after an infection, but these antibodies don't appear to explain why the autoimmune problems occur. The findings suggest that while these antibodies might be useful for diagnosis in some patients, they may not be the root cause of ME/CFS.

Evidence of aberrant anti-epstein-barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue.

Mouat, Isobel C, Zhu, Li, Aslan, Alperen et al.·Journal of inflammation (London, England)·2024

This study looked at whether Epstein-Barr virus (EBV), a common virus that stays dormant in most people's bodies, reactivates in stroke patients who experience severe fatigue. Researchers compared 44 stroke survivors—22 with high fatigue and 22 with low fatigue—and measured both the amount of active virus and antibodies against it in their blood. While they found that EBV reactivation happened equally in both groups, people with high fatigue showed unusual patterns in their immune response to the virus, suggesting their bodies may not be fighting EBV normally.

Plasma and peritoneal fluid cytokine profiles in patient with Essure® implant: Towards a molecular signature?

Garnier, Lorna, Parant, François, Bulteau, Claire et al.·European journal of obstetrics, gynecology, and reproductive biology·2024

Researchers measured inflammation markers (cytokines) in blood and fluid from the abdomen in women with Essure implants, women with endometriosis, and healthy controls. They found that women with Essure implants had higher levels of two specific inflammation markers (MCP-1 and TNF-α) in their blood compared to controls. These same markers are known to be elevated in fibromyalgia and chronic fatigue syndrome, suggesting they might be relevant to understanding Essure-related symptoms.

Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome.

Saito, Suguru, Shahbaz, Shima, Osman, Mohammed et al.·Journal of autoimmunity·2024

This study compared blood samples from long COVID patients with ME/CFS to those who fully recovered from COVID-19. Researchers found that ME/CFS patients had unusual patterns in their immune cells and higher levels of inflammation-promoting substances in their blood. They also discovered specific immune markers that could reliably distinguish ME/CFS patients from those who recovered, suggesting these markers could potentially be used for diagnosis.

E2 ModerateCohortPEM requiredCross-Sectional

Comparison of T-cell receptor diversity of people with myalgic encephalomyelitis versus controls.

Dibble, Joshua J, Ferneyhough, Ben, Roddis, Matthew et al.·BMC research notes·2024

Researchers studied immune cells called T-cells in people with ME/CFS to see if they were different from those in healthy people. They looked at genetic patterns in blood samples from 40 people in each group: those severely affected by ME/CFS, those mildly or moderately affected, people with multiple sclerosis, and healthy controls. Although they used advanced technology and computer programs to analyze the data, they found that the T-cell patterns were not notably different between the groups.

E2 ModerateCohortPEM unclearObservational

Synbiotic Supplementation Improves Quality of Life and Inmunoneuroendocrine Response in Patients with Fibromyalgia: Influence of Codiagnosis with Chronic Fatigue Syndrome.

Hinchado, María Dolores, Quero-Calero, Carmen Daniela, Otero, Eduardo et al.·Nutrients·2023

This study tested whether a probiotic supplement (containing beneficial bacteria) could help women with fibromyalgia, especially those who also had ME/CFS. After one month of taking the supplement, participants reported feeling less stressed, anxious, and depressed, and their quality of life improved. The supplement also appeared to help their body's stress response system work better.

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 SystemPost-Exertional Malaise

NeuroinflammationImmune System

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.

Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone.

Sun, Qian, Oltra, Elisa, Dijck-Brouwer, D A Janneke et al.·Redox biology·2023

Some people with ME/CFS have antibodies that attack a protein called selenoprotein P, which normally helps transport selenium (a mineral needed for thyroid function) throughout the body. This study found that ME/CFS patients with these antibodies have lower selenium levels and struggle to convert thyroid hormone into its active form, which could explain why they feel tired and have other thyroid-like symptoms even when standard thyroid tests appear normal.