Title: Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19
Author: Enrico Brunetta, Marco Folci, Barbara Bottazzi, Maria De Santis, Giuseppe Gritti, Alessandro Protti, Sarah N. Mapelli, Stefanos Bonovas, Daniele Piovani, Roberto Leone, Ilaria My, Veronica Zanon, Gianmarco Spata, Monica Bacci, Domenico Supino, Silvia Carnevale, Marina Sironi, Sadaf Davoudian, Clelia Peano, Francesco Landi, Fabiano Di Marco, Federico Raimondi, Andrea Gianatti, Claudio Angelini, Alessandro Rambaldi, Cecilia Garlanda, Michele Ciccarelli, Maurizio Cecconi, Alberto Mantovani
Abstract: Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1,2,3. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)4,5,6,7. RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.