Evidence browser

NeuroinflammationImmune System

Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation.

Theoharides, Theoharis C, Twahir, Assma, Kempuraj, Duraisamy·Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology·2024

This study examines mast cells, which are immune cells found throughout the body, and how they may be involved in conditions like ME/CFS that affect the nervous system and cause abnormal heart rate and blood pressure responses. Mast cells sit near nerve endings and important organs, where they can release chemicals that affect how the body regulates basic functions like temperature and blood pressure. The researchers suggest that controlling mast cell activation might help treat these conditions, though currently there are no proven treatments.

E3 PreliminaryMechanismPEM unclearObservational

A Pilot Study on the Effects of Exercise Training on Cardiorespiratory Performance, Quality of Life, and Immunologic Variables in Long COVID.

Abbasi, Asghar, Gattoni, Chiara, Iacovino, Michelina et al.·Journal of clinical medicine·2024

This study tested whether supervised aerobic exercise training could help people with long COVID. Fourteen participants completed 20 sessions of exercise training over 10 weeks. After training, people reported feeling less fatigued, less anxious and depressed, and had better heart and lung fitness—without experiencing harmful immune system changes.

Immune SystemPost-Exertional Malaise

E3 PreliminaryCohortPEM requiredCross-Sectional

Immune exhaustion in ME/CFS and long COVID.

Eaton-Fitch, Natalie, Rudd, Penny, Er, Teagan et al.·JCI insight·2024

This study looked at immune system genes in blood samples from people with ME/CFS and long COVID to understand why their immune systems aren't working properly. Researchers found that people with ME/CFS had reduced immune signaling and infection-fighting genes, suggesting immune suppression, while long COVID patients showed different patterns of immune dysregulation. These findings suggest that both conditions involve problems with how the immune system activates and responds, which may help explain why people with these illnesses struggle with persistent symptoms.

NeuroinflammationImmune SystemPost-Exertional Malaise

A Narrative Review on Gut Microbiome Disturbances and Microbial Preparations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Long COVID.

Jurek, Joanna Michalina, Castro-Marrero, Jesus·Nutrients·2024

This review examines how changes in gut bacteria may contribute to ME/CFS and long COVID symptoms, and whether taking probiotics or similar microbial preparations might help. The authors looked at existing research to understand the connection between gut health and the brain-immune system, and whether restoring healthy gut bacteria could reduce fatigue, inflammation, and other symptoms in these conditions.

E3 PreliminaryMechanismPEM not requiredMechanistic

Effect of electroacupuncture on behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome.

Qu, Yuan-Yuan, Feng, Chu-Wen, Sun, Zhong-Ren et al.·Zhen ci yan jiu = Acupuncture research·2024

Researchers tested whether electroacupuncture—a traditional needle-based treatment—could help rats with experimentally-induced fatigue syndrome. The treated rats showed improved physical endurance, better memory, and reduced anxiety compared to untreated sick rats. The researchers also found that treatment reduced inflammatory markers in the brain and blood that were elevated in sick rats.

NeuroinflammationImmune System

E3 PreliminaryMechanismPEM not requiredMechanistic

An Exercise Immune Fitness Test to Unravel Disease Mechanisms-A Proof-of-Concept Heart Failure Study.

Bondar, Galyna, Mahapatra, Abhinandan Das, Bao, Tra-Mi et al.·Journal of clinical medicine·2024

This study examined how genes in immune cells respond to exercise in people with heart failure and healthy volunteers. Researchers took blood samples before, during, and after exercise on a stationary bike and looked for changes in gene activity. They found that certain genes responded differently to exercise depending on how fit someone was, suggesting that gene patterns might help doctors understand exercise capacity and predict outcomes.

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Identification of stimuli that enhance human herpesvirus 6A (HHV-6A) replication and reconstitution.

Reich, Jana, Serdar, Dilan, Weißmann, Ann-Christin et al.·Journal of virology·2024

This study focuses on improving laboratory techniques for studying HHV-6A, a common virus that stays dormant in the body for life. Researchers tested different methods to grow this virus in the lab more efficiently, discovering that certain immune-suppressing drugs and low-oxygen conditions help the virus replicate better. While this doesn't directly treat ME/CFS patients, understanding how HHV-6A behaves in the lab is an important step toward developing better treatments.

Potential pathophysiological role of the ion channel TRPM3 in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the therapeutic effect of low-dose naltrexone.

Löhn, Matthias, Wirth, Klaus Josef·Journal of translational medicine·2024

This study explores how a specific ion channel called TRPM3, which helps control pain signals and immune cell function, may not work properly in ME/CFS patients. The researchers found that immune cells called natural killer cells have reduced function due to TRPM3 problems, and a medication called low-dose naltrexone (LDN) may help restore this function in laboratory tests. This could explain why some ME/CFS patients report feeling better with LDN treatment.

Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing.

Zheng, Daisi, Li, Xiaolong, Wang, Peicheng et al.·Frontiers in immunology·2024

Researchers discovered that ME/CFS and lupus (SLE) may share similar immune problems, particularly involving immune cells called monocytes that become overactive and produce excess inflammation. By studying genes and immune cells from both diseases, they identified five key inflammatory proteins that appear important in fatigue, and they predict that certain existing drugs—particularly N-acetyl-L-cysteine and camptothecin—might help reduce this inflammation.

Sex differences in vascular endothelial function related to acute and long COVID-19.

Kitselman A, Kayla, Bédard-Matteau, Jérôme, Rousseau, Simon et al.·Vascular pharmacology·2024

This review examines how COVID-19 and long COVID affect blood vessel health differently in men and women. The authors look at how the virus can damage the inner lining of blood vessels, trigger immune problems, and potentially lead to ME/CFS symptoms. They explore whether biological sex differences explain why some people recover while others develop long-term symptoms like fatigue.

Energy MetabolismImmune System

Dysregulation of tetrahydrobiopterin metabolism in myalgic encephalomyelitis/chronic fatigue syndrome by pentose phosphate pathway.

Bulbule, Sarojini, Gottschalk, Carl Gunnar, Drosen, Molly E et al.·Journal of central nervous system disease·2024

Researchers found that patients with ME/CFS who experience dizziness upon standing have abnormally high levels of certain molecules called biopterins in their blood. The study discovered that these molecules are produced through an unusual metabolic pathway involving the breakdown of glucose, and this pathway appears to trigger inflammation in immune cells. This finding suggests a potential biochemical explanation for some ME/CFS symptoms.

E3 PreliminaryMechanismPEM not requiredMechanistic

Lacticaseibacillus rhamnosus Strains for Alleviation of Irritable Bowel Disease and Chronic Fatigue Syndrome.

Zhang, Liang, Ni, Xue, Jiang, Minzhi et al.·Microorganisms·2024

Researchers studied special strains of a probiotic bacteria called Lacticaseibacillus rhamnosus to see if they could help with ME/CFS and irritable bowel syndrome (IBS). After testing 21 different strains, they found that two strains (WL11 and WL17) reduced fatigue-related symptoms like weight loss, anxiety, and memory problems in mice with CFS-like illness, and also eased IBS symptoms like gut sensitivity and inflammation. However, these results are from animal studies, so we don't yet know if the same effects will work in people.

Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target.

Sasso, Etianne Martini, Muraki, Katsuhiko, Eaton-Fitch, Natalie et al.·Frontiers in immunology·2024

This study looked at a tiny channel (called TRPM3) that sits on immune cells called NK cells, which help fight infections. Researchers found that both ME/CFS and post-COVID patients have a broken version of this channel. Importantly, they discovered that a drug called naltrexone (NTX) could fix this broken channel in lab-grown cells from post-COVID patients, suggesting it might help real patients feel better.

E3 PreliminaryCohortPEM unclearCase-Control

Clinical Remission After Therapeutic Apheresis in a Patient Suffering from Long Term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case Report.

Burgard, Harald·International medical case reports journal·2024

This case report describes one woman with ME/CFS for over 15 years who underwent a blood-cleaning treatment called double-filtration apheresis eight times over two years. After treatment, she experienced significant improvement in her fatigue, thinking problems, and other symptoms, with benefits that lasted over time. While this is promising, it is based on just one patient's experience and needs much larger studies to confirm whether this treatment works for others with ME/CFS.

The potential role of ocular and otolaryngological mucus proteins in myalgic encephalomyelitis/chronic fatigue syndrome.

Huitsing, Kaylin, Tritsch, Tara, Arias, Francisco Javier Carrera et al.·Molecular medicine (Cambridge, Mass.)·2024

This study explores why people with ME/CFS often experience dry eyes, sore throats, and stuffy noses. Researchers investigated whether problems with mucin proteins—substances that create protective layers in your mouth, nose, and eyes—might contribute to ME/CFS symptoms. Using computer analysis and genetic data, they hypothesized that weakened mucus membranes could lead to chronic inflammation in these areas, potentially worsening the condition.

Energy MetabolismImmune System

Widespread Myalgia and Chronic Fatigue: Phagocytes from Macrophagic Myofasciitis Patients Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit Specific Inflammatory, Autophagic, and Mitochondrial Responses.

Masson, Jean-Daniel, Badran, Ghidaa, Gherardi, Romain K et al.·Toxics·2024

This study examined immune cells from people with macrophagic myofasciitis (MMF), a condition involving long-term inflammation from vaccine aluminum adjuvants lodged in muscle tissue. Researchers found that these immune cells behave abnormally when exposed to aluminum adjuvants: they produce more pain-causing molecules, show signs of energy exhaustion, and struggle to respond to their normal workload. These findings suggest a possible mechanism for why MMF patients develop severe fatigue and widespread muscle pain similar to ME/CFS.

Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis.

Ruiz-Pablos, Manuel, Paiva, Bruno, Zabaleta, Aintzane·Frontiers in immunology·2024

This review proposes that ME/CFS, long COVID, and post-vaccine syndrome may share a common cause: an immune system problem that damages the pituitary gland (a small gland that controls many hormones). The researchers suggest that in genetically susceptible people, a weak initial response to viruses can lead to an overactive immune response that mistakenly attacks the body's own pituitary gland, lowering levels of crucial hormones like cortisol. They propose that treatments like antivirals, steroids, and antioxidants might help by reducing inflammation and restoring hormone balance.