As of 20 November 2020, the number of COVID-19 cases was reported to be more than 57 million, leading to more than 1.361,000 deaths worldwide .

Elevated levels of CRP, cytokine and chemokines, together with low lymphocyte and eosinophil counts, characterize patients with severe disease. However, a reliable biomarker of poor outcome in COVID-19 is still lacking.

The early and accurate triaging of the patients may contribute to better patient management and stratification in clinical trials. The present study, published on Nature Immunology by researchers of Milan and Bergamo, was designed to investigate expression and clinical significance of the
fluid-phase pattern-recognition receptor PTX3 in COVID-19.

The authors found that PTX3 was induced by SARS-CoV-2 in respiratory
tract epithelial cells. In patients with COVID-19, PTX3 analyzed in bulk and at single-cell level was selectively expressed by monocytes among circulating cells and by lung macrophages, as well as by endothelial cells by immunohistochemistry.

High PTX3 plasma levels were a strong independent indicator of short-term 28-d mortality. In this patient cohort, PTX3 fared substantially better than
other known prognostic markers, including CRP, IL-6, ferritin and D-dimer.

PTX3 is produced by diverse cell types including myelomonocytic cells, lung epithelial cells and endothelial cells. In the present study, it was found that SARS-CoV-2 induced gene expression of PTX3 in respiratory tract epithelial cells. Using bulk RNA-seq and bioinformatic analysis at single-cell level, the autors found that PTX3 was selectively expressed by monocytes among circulating leukocytes. Moreover, in lung BALF, single-cell analysis on public databases revealed selective expression of PTX3 in neutrophils and macrophages.
PTX3 was originally cloned in endothelial cells and vascular cells are a major source of this component of humoral innate classifiers or prognostic indicators. In two independent patient cohorts, early in disease progression, PTX3 was a strong prognostic indicator of short-term death,
a hard end point, better than other markers such as IL-6 and CRP.
The strong prognostic significance of PTX3 for short-term mortality reflects its production by myeloid cells and endothelial cells in the lungs.

The results reported suggest that PTX3 may serve as an early low-cost/low-tech biomarker for patient management, follow-up and stratification
in clinical trials.