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

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

doi:10.3389/fimmu.2023.1085610

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

Front Immunol. 2023 May 3:14:1085610. doi: 10.3389/fimmu.2023.1085610. eCollection 2023.

Authors

Dorian Forte¹, Roberto Maria Pellegrino², Sara Trabanelli^{3

4}, Tommaso Tonetti^{5

6}, Francesca Ricci⁷, Mara Cenerenti^{3

4}, Giorgia Comai⁸, Pierluigi Tazzari⁷, Tiziana Lazzarotto^{5

9}, Sandra Buratta², Lorena Urbanelli², Ghazal Narimanfar¹, Husam B R Alabed², Cristina Mecucci¹⁰, Gaetano La Manna⁸, Carla Emiliani², Camilla Jandus^{3

4}, Vito Marco Ranieri^{5

6}, Michele Cavo^{1

11}, Lucia Catani^{1

11}, Francesca Palandri¹¹

Affiliations

¹ Department of Medical and Surgical Sciences (DIMEC), Institute of Hematology 'Seràgnoli', University of Bologna, Bologna, Italy.
² Department of Chemistry, Biology and Biotechnology, Biochemistry and Molecular Biology Section, University of Perugia, Perugia, Italy.
³ Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
⁴ Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland.
⁵ Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
⁶ Anesthesia and Intensive Care Medicine, IRCCS Azienda Ospealiero-Universitaria di Bologna, Bologna, Italy.
⁷ Immunohematology and blood bank, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁸ Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁹ Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
¹⁰ Department of Medicine and Surgery, Center for Hemato-Oncology Research (C.R.E.O.), University of Perugia, Perugia, Italy.
¹¹ Istituto di Ematologia "Seràgnoli", IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Abstract

Introduction: 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.

Methods: Peripheral blood (PB) was collected from COVID-19 patients (n=10) and HC (n=10). EPs were purified from platelet-poor plasma by size exclusion chromatography (SEC) and ultrafiltration. Plasma cytokines and EPs were characterized by multiplex bead-based assay. Quantitative lipidomic profiling of EPs was performed by liquid chromatography/mass spectrometry combined with quadrupole time-of-flight (LC/MS Q-TOF). Innate lymphoid cells (ILC) were characterized by flow cytometry after co-cultures with HC-EPs or Co-19-EPs.

Results: 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 cells (ILC2) cytokine secretion. As a consequence, ILC2 from severe COVID-19 patients show a more activated phenotype due to the presence of Co-19-EPs.

Discussion: 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.

Keywords: COVID-19; SARS-CoV-2; extracellular vesicles and particles; innate lymphoid cells; lipidomic; type 2 innate lymphoid cell.

Copyright © 2023 Forte, Pellegrino, Trabanelli, Tonetti, Ricci, Cenerenti, Comai, Tazzari, Lazzarotto, Buratta, Urbanelli, Narimanfar, Alabed, Mecucci, La Manna, Emiliani, Jandus, Ranieri, Cavo, Catani and Palandri.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Cytokines
Humans
Immunity, Innate
Lymphocytes
Oxygen

Substances

Cytokines
Oxygen

Grants and funding

DF was supported by Fondazione Umberto Veronesi. This research was funded by Olga Mayenfish Foundation. This work was also supported by Fondazione Cassa di Risparmio di Bologna (CARISBO).