Evidence browser

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.

E3 PreliminaryMechanismPEM unclearCase-Control

Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series.

Gil, Anna, Hoag, George E, Salerno, John P et al.·Brain, behavior, & immunity - health·2024

This study found that people with ME/CFS and Long COVID have immune cells (called CD8 T-cells) that don't work properly—they can't produce certain protective substances as well as healthy people can. The researchers also tested a nebulized (inhaled) treatment made from five natural antioxidant ingredients in a small group of patients and found that both the immune cell function and symptom severity improved over time with treatment, without serious side effects.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Sjögren's syndrome.

Balint, Geza, Watson Buchanan, W, Kean, Colin A et al.·Inflammopharmacology·2024

Sjögren's syndrome is an autoimmune disease that causes dry eyes and dry mouth, often with swollen salivary glands. This review article explains that Sjögren's syndrome can occur on its own or alongside other autoimmune diseases like lupus or rheumatoid arthritis. Importantly, the authors note that Sjögren's syndrome has been linked to chronic fatigue syndrome and fibromyalgia, suggesting there may be shared features between these conditions.

E3 PreliminaryCohortPEM unclearCase-Control

Successful Subcutaneous Immunoglobulin Therapy in a Case Series of Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Sjogren, Per, Bragée, Bjorn, Britton, Sven·Clinical therapeutics·2024

This study tested a treatment called subcutaneous immunoglobulin (a protein that helps the immune system) in 17 ME/CFS patients whose symptoms seemed to be triggered by infections. After 5 weeks of treatment, patients reported significant improvements in their symptoms, quality of life, and ability to work, with no serious side effects. One patient reported their ME/CFS symptoms disappeared completely.

Immune SystemNeuroinflammation

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

This study in rats observed that electroacupuncture applied to specific head points was associated with improvements in fatigue-like behaviour and learning/memory tasks, alongside changes in inflammatory markers in the brain and blood. The researchers propose that these changes may relate to altered inflammation in the central nervous system; however, this is an animal study and findings have not yet been tested in humans with ME/CFS.

Immune SystemNeuroinflammation

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.

Energy MetabolismImmune System

Suppressed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome.

Uhde, Melanie, Indart, Alyssa C, Green, Peter H R et al.·Brain, behavior, & immunity - health·2023

This study found that people with ME/CFS have a weakened immune response to bacteria that leak through a damaged gut lining, along with unusual changes in how their bodies process glucose and other nutrients. The immune system appears to be suppressed in some ways while overactive in others, and these patterns were linked to metabolic changes. These findings suggest that gut health and metabolic dysfunction may play important roles in ME/CFS symptoms.

Potential molecular mechanisms of chronic fatigue in long haul COVID and other viral diseases.

Gottschalk, Carl Gunnar, Peterson, Daniel, Armstrong, Jan et al.·Infectious agents and cancer·2023

This review article examines how viral infections—including long COVID, EBV, and others—can trigger severe, lasting fatigue and related symptoms. The authors explore the biological mechanisms that might explain why some patients develop chronic muscle fatigue and brain fog after viral illness, and compare these processes to ME/CFS. This research suggests that multiple different viruses may cause fatigue through similar pathways in the body.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Pushing the envelope: Immune mechanism and application landscape of macrophage-activating lipopeptide-2.

Liao, Daoyong, Su, Xiaoling, Wang, Jingyun et al.·Frontiers in immunology·2023

This review examines how a molecule called MALP-2, derived from a bacterium linked to ME/CFS, affects the immune system. Researchers found that MALP-2 can activate immune cells in ways that might help fight infections and heal tissues. The molecule is simple to make and could potentially be developed into treatments for various conditions.

Energy MetabolismImmune System

Genetic risk factors for severe and fatigue dominant long COVID and commonalities with ME/CFS identified by combinatorial analysis.

Taylor, Krystyna, Pearson, Matthew, Das, Sayoni et al.·Journal of translational medicine·2023

Researchers studied the genetic differences between people with long COVID to understand why some develop severe symptoms while others mainly experience extreme fatigue. They found that certain genetic variations, especially in genes related to brain function and metabolism, may influence how the disease develops. Importantly, they discovered that some of the same genetic patterns appear in both long COVID and ME/CFS patients, suggesting these conditions may share similar underlying biological mechanisms.

Epstein-Barr virus-acquired immunodeficiency in myalgic encephalomyelitis-Is it present in long COVID?

Ruiz-Pablos, Manuel, Paiva, Bruno, Zabaleta, Aintzane·Journal of translational medicine·2023

This study proposes that a virus called Epstein-Barr virus (EBV) may play a central role in both ME/CFS and long COVID by gradually weakening the immune system. The researchers suggest that in people with certain genetic traits, EBV can hide in various body tissues and repeatedly reactivate, causing ongoing inflammation and exhaustion of the immune system. They hypothesize that long COVID may follow a similar pattern, possibly starting with a COVID-19 infection in people whose immune systems struggle to control EBV.

A pilot study on the immune cell proteome of long COVID patients shows changes to physiological pathways similar to those in myalgic encephalomyelitis/chronic fatigue syndrome.

Peppercorn, Katie, Edgar, Christina D, Kleffmann, Torsten et al.·Scientific reports·2023

This small pilot study looked at immune cells from long COVID patients and compared them to healthy people, analyzing thousands of proteins in their blood. They found that long COVID patients had significant differences in their immune cell proteins, particularly in how their bodies handle energy production and immune function—similar patterns to what researchers have seen in ME/CFS. This suggests that long COVID and ME/CFS may share similar underlying biological problems, even though they start from different triggers.

E3 PreliminaryMechanismPEM requiredMechanistic

Stress-Induced Transcriptomic Changes in Females with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Reveal Disrupted Immune Signatures.

Van Booven, Derek J, Gamer, Jackson, Joseph, Andrew et al.·International journal of molecular sciences·2023

This study looked at how the bodies of women with ME/CFS respond to exercise compared to healthy women. Researchers collected blood samples at three points: before exercise, during maximum effort, and during recovery. While healthy women's immune cells showed normal changes during exercise, women with ME/CFS showed unusual immune system activity specifically during the recovery period—the time when post-exertional malaise (worsening of symptoms) typically occurs.

Immune SystemPost-Exertional Malaise

E3 PreliminaryMechanismPEM requiredObservational

Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis.

Achleitner, Martin, Steenblock, Charlotte, Dänhardt, Juliane et al.·Molecular psychiatry·2023

Researchers tested a treatment called therapeutic apheresis (a blood-cleaning procedure) in Long-COVID patients and found that those who improved had significant reductions in harmful immune molecules, fatty substances, and inflammatory markers in their blood. The study also showed that a blood protein called fibrinogen dropped by 70% after treatment, and abnormal blood clumping patterns disappeared. This suggests the treatment may work by removing specific harmful substances from the blood.

Immune SystemPost-Exertional Malaise

E3 PreliminaryCohortPEM unclearCross-Sectional

Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC).

Paniskaki, Krystallenia, Goretzki, Sarah, Anft, Moritz et al.·Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology·2023

This study looked at children who had COVID-19 and developed long-lasting symptoms like breathing problems, fatigue, and brain fog—a condition called pediatric long COVID. Researchers found that these children had more immune cells fighting the virus that were less effective than usual, and these cells released inflammatory chemicals that may have been causing their symptoms. The findings suggest that ongoing immune system activation after COVID-19 might explain why some children develop persistent health problems similar to ME/CFS.

In vitro B cell experiments explore the role of CD24, CD38, and energy metabolism in ME/CFS.

Armstrong, Christopher W, Mensah, Fane F K, Leandro, Maria J et al.·Frontiers in immunology·2023

This study examined immune cells called B cells from ME/CFS patients and healthy people to understand how they handle energy differently. Researchers found that B cells from ME/CFS patients struggle to produce enough energy and have to work harder, using more nutrients to keep functioning. These cells also showed signs of being under stress, which may help explain why ME/CFS patients feel exhausted.

Immune SystemNeuroinflammation

Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID.

Tate, Warren P, Walker, Max O M, Peppercorn, Katie et al.·International journal of molecular sciences·2023

ME/CFS is a complex illness that typically starts after a viral infection, though other stressful events can also trigger it. This review explains that different patients experience different combinations of symptoms and respond differently to treatments—what helps one person may not help another. The authors discuss how the immune system may shift from a temporary response to a lasting problem, and how the brain's immune system may cause the neurological symptoms people experience.

E3 PreliminaryMechanismPEM requiredMechanistic

Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Maya, Jessica, Leddy, Sabrina M, Gottschalk, C Gunnar et al.·International journal of molecular sciences·2023

Researchers studied immune cells called lymphocytes from ME/CFS patients and found that these cells use fatty acids (a type of fuel) differently than healthy people's immune cells do. When immune cells are activated or working hard, ME/CFS patients' cells rely more heavily on burning fat for energy compared to cells from healthy controls. This suggests that ME/CFS patients' immune systems may have a fundamental problem with how they fuel their cells.

Energy MetabolismImmune System

Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases?

Kell, Douglas B, Pretorius, Etheresia·The Biochemical journal·2023

This study proposes that in Long COVID and other post-infection diseases, a blood protein called fibrinogen can fold into an abnormal shape that forms sticky clots called fibrinaloids. These unusual clots may trigger the immune system to attack the body's own tissues (autoimmunity) because the abnormal folding creates new structures the immune system doesn't recognize. The authors suggest this process is similar to what happens in prion diseases and other protein-misfolding conditions.