Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19.

Brunetta, Enrico; Folci, Marco; Bottazzi, Barbara; De Santis, Maria; Gritti, Giuseppe; Protti, Alessandro; Mapelli, Sarah N; Bonovas, Stefanos; Piovani, Daniele; Leone, Roberto; My, Ilaria; Zanon, Veronica; Spata, Gianmarco; Bacci, Monica; Supino, Domenico; Carnevale, Silvia; Sironi, Marina; Davoudian, Sadaf; Peano, Clelia; Landi, Francesco; Di Marco, Fabiano; Raimondi, Federico; Gianatti, Andrea; Angelini, Claudio; Rambaldi, Alessandro; Garlanda, Cecilia; Ciccarelli, Michele; Cecconi, Maurizio; Mantovani, Alberto

Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1-3. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)4-7. 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.