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Nature immunology
01, 2021;22 (1): 19-24.

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

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
Author Information
  1. Enrico Brunetta: Humanitas Clinical and Research Center-IRCCS, Milan, Italy. ORCID
  2. Marco Folci: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  3. Barbara Bottazzi: Humanitas Clinical and Research Center-IRCCS, Milan, Italy. ORCID
  4. Maria De Santis: Humanitas Clinical and Research Center-IRCCS, Milan, Italy. ORCID
  5. Giuseppe Gritti: Unit of Hematology, Azienda Ospedaliera Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy. ORCID
  6. Alessandro Protti: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  7. Sarah N Mapelli: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  8. Stefanos Bonovas: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  9. Daniele Piovani: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  10. Roberto Leone: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  11. Ilaria My: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  12. Veronica Zanon: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  13. Gianmarco Spata: Humanitas Clinical and Research Center-IRCCS, Milan, Italy. ORCID
  14. Monica Bacci: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  15. Domenico Supino: Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  16. Silvia Carnevale: Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  17. Marina Sironi: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  18. Sadaf Davoudian: Humanitas Clinical and Research Center-IRCCS, Milan, Italy. ORCID
  19. Clelia Peano: Humanitas Clinical and Research Center-IRCCS, Milan, Italy. ORCID
  20. Francesco Landi: Unit of Hematology, Azienda Ospedaliera Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.
  21. Fabiano Di Marco: Unit of Pneumology, Azienda Ospedaliera Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.
  22. Federico Raimondi: Unit of Pneumology, Azienda Ospedaliera Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.
  23. Andrea Gianatti: Unit of Pathology, Azienda Ospedaliera Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy. ORCID
  24. Claudio Angelini: Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  25. Alessandro Rambaldi: Unit of Hematology, Azienda Ospedaliera Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy. arambaldi@asst-pg23.it. ORCID
  26. Cecilia Garlanda: Humanitas Clinical and Research Center-IRCCS, Milan, Italy. cecilia.garlanda@humanitasresearch.it. ORCID
  27. Michele Ciccarelli: Humanitas Clinical and Research Center-IRCCS, Milan, Italy. michele.ciccarelli@humanitas.it. ORCID
  28. Maurizio Cecconi: Humanitas Clinical and Research Center-IRCCS, Milan, Italy. maurizio.cecconi@humanitas.it. ORCID
  29. Alberto Mantovani: Humanitas Clinical and Research Center-IRCCS, Milan, Italy. alberto.mantovani@humanitasresearch.it. ORCID
PMID: 33208929 DOI: 10.1038/s41590-020-00832-x

Abstract

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

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Grants

  1. H2020-MSCA-ITN-2015/European Commission (EC)

MeSH Term

A549 Cells
Adult
C-Reactive Protein
COVID-19
Cell Line, Tumor
Cells, Cultured
Cohort Studies
Endothelial Cells
Epidemics
Female
Gene Expression Profiling
Humans
Macrophages
Male
Middle Aged
Monocytes
Neutrophils
Prognosis
SARS-CoV-2
Serum Amyloid P-Component

Chemicals

Serum Amyloid P-Component
PTX3 protein
C-Reactive Protein
Journal Article Research Support, Non-U.S. Gov't

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