AUTHOR=Forte Dorian , Pellegrino Roberto Maria , Trabanelli Sara , Tonetti Tommaso , Ricci Francesca , Cenerenti Mara , Comai Giorgia , Tazzari Pierluigi , Lazzarotto Tiziana , Buratta Sandra , Urbanelli Lorena , Narimanfar Ghazal , Alabed Husam B. R. , Mecucci Cristina , La Manna Gaetano , Emiliani Carla , Jandus Camilla , Ranieri Vito Marco , Cavo Michele , Catani Lucia , Palandri Francesca 

TITLE=Circulating extracellular particles from severe COVID-19 patients show altered profiling and innate lymphoid cell-modulating ability

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1085610

DOI=10.3389/fimmu.2023.1085610

ISSN=1664-3224

ABSTRACT=Extracellular vesicles (EVs) and particles (EPs) represent reliable biomarkers for disease detection. Their role in the inflammatory microenvironment of severe COVID-19 patients is not well determined. Here, we characterized the immunophenotype, the lipidomic cargo and the functional activity of circulating EPs from severe COVID-19 patients (Co-19-EPs) and healthy controls (HC EPs) correlating the data with the clinical parameters including the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) and the sequential organ failure assessment (SOFA) score. We observed that EPs from severe COVID-19 patients: 1) display an altered surface signature as assessed by multiplex protein analysis; 2) are characterized by distinct lipidomic profiling; 3) show correlations between lipidomic profiling and disease aggressiveness scores; 4) fail to dampen type 2 innate lymphoid cell (ILC2s) cytokine secretion. As a consequence, ILC2s from severe COVID-19 patients show a more activated phenotype. In summary, these data highlight that abnormal circulating EPs promote  ILC2-driven inflammatory signals in severe COVID-19 patients and support further exploration to unravel the role of EPs (and EVs) in COVID-19 pathogenesis.