Neutrophil Extracellular Traps in COVID-19

Zuo, Y., Yalavarthi, S., Shi, H., Gockman, K., Zuo, M., Madison, J.A., Blair, C.N., Weber, A., Barnes, B.J., Egeblad, M., Woods, R.J., Kanthi, Y., Knight, J.S. (June 2020) Neutrophil Extracellular Traps in COVID-19. JCI Insight, 5 (11). p. 138999. ISSN 2379-3708

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Abstract

In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. While elevated levels of blood neutrophils predict worse outcomes in COVID-19, the role of NETs has not been investigated. We now report that sera from patients with COVID-19 (n = 50 patients, n = 84 samples) have elevated levels of cell-free DNA, myeloperoxidase(MPO)-DNA, and citrullinated histone H3 (Cit-H3); the latter two are highly specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute phase reactants including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. In summary, these data reveal high levels of NETs in many patients with COVID-19, where they may contribute to cytokine release and respiratory failure. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts, and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification diseases & disorders > viral diseases organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions diseases & disorders > viral diseases > coronavirus diseases & disorders > viral diseases > coronavirus > covid 19 bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > histone organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:	Egeblad, Mikala
Communities:	CSHL labs > Egeblad lab CSHL Cancer Center Program > Cellular Communication in Cancer Program
Depositing User:	Adrian Gomez
Date:	4 June 2020
Date Deposited:	07 May 2020 13:57
Last Modified:	01 Feb 2024 19:55
PMCID:	PMC7308057
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/39344

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