Neutrophil extracellular traps in COVID-19

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 p...

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Published in:JCI insight Vol. 5; no. 11
Main Authors: Zuo, Yu, Yalavarthi, Srilakshmi, Shi, Hui, Gockman, Kelsey, Zuo, Melanie, Madison, Jacqueline A., Blair, Christopher N., Weber, Andrew, Barnes, Betsy J., Egeblad, Mikala, Woods, Robert J., Kanthi, Yogendra, Knight, Jason S.
Format: Journal Article
Language:English
Published: United States American Society for Clinical Investigation 04.06.2020
Subjects:
Adult
Aged
Aged, 80 and over
Biomarkers
Blood platelets
C-reactive protein
C-Reactive Protein - metabolism
Case-Control Studies
Cell-Free Nucleic Acids - metabolism
Chromatin
Citrullination
Citrulline
Coronavirus Infections - blood
Coronavirus Infections - metabolism
Coronavirus Infections - therapy
Coronaviruses
COVID-19
Cytokines
Dehydrogenases
Deoxyribonucleic acid
Disease
DNA
Enzymes
Extracellular Traps - metabolism
Female
Fibrin Fibrinogen Degradation Products - metabolism
Histone H3
Histones
Histones - metabolism
Hospitalization
Humans
In Vitro Techniques
Infections
Influenza
L-Lactate dehydrogenase
L-Lactate Dehydrogenase - metabolism
Leukocytes (neutrophilic)
Lymphocyte Count
Male
Mann-Whitney U test
Mechanical ventilation
Medical laboratories
Microbicides
Microvasculature
Middle Aged
Neutrophils
Neutrophils - metabolism
Oxidants
Pandemics
Patients
Peroxidase
Peroxidase - metabolism
Platelet Count
Pneumonia
Pneumonia, Viral - blood
Pneumonia, Viral - metabolism
Pneumonia, Viral - therapy
Respiration, Artificial
Respiratory distress syndrome
Respiratory failure
Severe acute respiratory syndrome coronavirus 2
Severity of Illness Index
Therapeutic targets
Thrombosis
Ventilators
Infectious disease
Inflammation
Neutrophils
ISSN:2379-3708, 2379-3708
Online Access:Get full text
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Summary: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 the potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. We now report that sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3); the latter 2 are 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. 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.
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ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.138999