Biomarkers and Mechanisms Associated with Endothelial Dysfunction and Hypoperfusion in Post-infectious ME/CFS

Prof. Dr. Martina Seifert talked about the work of her group on furthering the understanding of vascular and endothelial cell dysregulation in ME/CFS and post-COVID syndrome. Findings point to the contribution of infections to, among others, endothelial senescence and changes in micro ribonucleic acid (RNA) profiles. Micro clots could also contribute to a disturbed blood flow as well as autoantibodies that might induce mitochondrial changes. Such changes may impair endothelial function in large and small vessels, inducing cerebral hypoperfusion, orthostatic intolerance and autonomic dysfunction. In their work, her group begun by treating endothelial cells with serum from post-COVID patients with and without ME/CFS as well as controls. The results revealed increased endothelial cell specific antibodies in the patient cohorts. Next, they analysed the serum for vascular inflammation and neutrophil markers and were able to identify markers for apoptosis and neutrophil extracellular trap (NET) activation. The group was able to discriminate between patients which had a COVID-19-associated disease onset and patients who fell ill after other infections, correlating selected markers with clinical parameters like post-exertional Malaise (PEM) and fatigue or dizziness. The research team went on to investigate additional components in the serum which may be involved in a large study with healthy controls, by looking at the extracellular vesicles in plasma and serum. By undertaking a protein search by mass spectrometry, they revealed a difference in down or upregulated proteins between post-COVID and other infectious-onset disease. Some identified and verified markers included insulin growth factor acid soluble unit (IGFALS), thrombospondin, and hemoglobin alpha chain. To further elaborate on what may cause vascular inflammation in the post-infectious disease, the research also looked at the microRNA profile of plasma vesicles, finding a strong correlation with several clinical scores covering fatigue, the immune system, muscles am, joint pain. MicroRNA downregulation in the investigated patients could indeed lead to an insufficiently regulated immune response and persistent low-grade inflammation. The findings could enable the development of potential biomarkers involved in vascular dysfunction and hypoxia-induced changes in post-infectious disease patients.