From Blood to Gut: Exploring the Diagnostic and Prognostic Potential of Extracellular Vesicles in Chronic Inflammatory and Neuropsychiatric Diseases

Extracellular vesicles (EVs) are double-membrane lipid nanoparticles released by all cell types, whose cargo of metabolites, RNA, DNA and proteins mirrors the physiological or pathological state of the cell of origin. This makes EVs promising diagnostic, prognostic and predictive biomarkers. This Ph.D. thesis explores how EVs can reshape diagnostic and prognostic workflows in clinical settings by identifying disease-specific signatures across different conditions.The first chapter investigates the prognostic value of blood-derived EVs, particularly platelet-derived EVs (PLT-EVs), in COVID-19. Using a lab-validated method for rapid EV identification directly from blood or plasma, we found that patients with a worse outcome after one week in intensive care exhibited higher PLT-EV levels.The second chapter focuses on post-acute sequelae of SARS-CoV-2 infection (PASC), in which patients from our cohort developed persistent symptoms months after recovery. Through activation-induced marker (AIM) assays and dextramers, we identified in PBMCs of PASC patients a hyperactivation of the CD4+ compartment and higher levels of SARS-CoV-2-specific CD8+ T cells compared with healthy controls.The third chapter examines blood- and gut-derived EVs as mediators of gut-brain axis communication in major depressive disorder and multiple sclerosis. We set up and optimized a fast, reliable method to isolate gut-derived EVs and revealed a specific EV fingerprint in both diseases.Overall, this work positions EVs as versatile tools for diagnosis and prognosis across multiple disorders. The methodologies developed here provide a foundation for future translational research, with implications for personalized medicine and biomarker-driven disease management.