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Published on: May 12, 2023
Implication of Neutrophils Extracellular Traps in the Pathogenesis of SARS-CoV-2 pneumonia
Patricia Pérez-Guerrero1, Francisco Illanes-Álvarez1, Denisse Márquez-Ruiz1
1Servicio de Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain.
Abstract:
Peripheral blood polymorphonuclear neutrophils (PMNs) forming extracellular traps (NETs), as well as endothelial- and platelet-derived parameters, have been analyzed in patients with SARS-CoV-2 pneumonia, and their prognostic role has been evaluated. Eighty-seven consecutive patients hospitalized with SARS-CoV-2 pneumonia were prospectively selected. A sample of 30 healthy individuals served as the control group. Clinical and oxygenation (oxygen saturation to fraction of inspired oxygen ratio-SpO2/FiO2) characteristics and PMNs forming NETs, serum levels of myeloperoxidase, E-selectin, vascular cell adhesion molecule 1-VCAM1-vascular endothelial growth factor, P-selectin, platelet factor 4 and plasma concentrations of D-dimer were evaluated at hospital admission, at discharge and 14 days after discharge. Intensive care unit admission or death was the primary composite endpoint. Patients showed a higher number of PMNs forming NETs than healthy controls. The absolute number of PMNs forming NETs was inversely correlated with oxygen status (SpO2/FiO2) and positively with inflammatory (C-reactive protein, ferritin) markers and VCAM1. A decrease in, but not a normalization of NETs and endothelial-derived parameters was observed in patients who survived. In conclusion, the formation of NETs runs parallel to that of other inflammatory and endothelial activation markers, and is inverse to the oxygenation parameters, supporting a pathogenic role for PMNs in this entity.
Insights
Neutrophil extracellular traps (NETs) and endothelial markers are elevated in SARS-CoV-2 pneumonia, correlating with poor oxygenation and inflammation. These markers decrease but do not normalize in survivors, suggesting a pathogenic role.
Area of Science:
- Immunology
- Pathophysiology
- Critical Care Medicine
Background:
- SARS-CoV-2 pneumonia is associated with systemic inflammation and endothelial dysfunction.
- Polymorphonuclear neutrophils (PMNs) forming neutrophil extracellular traps (NETs) have been implicated in various inflammatory conditions.
- The prognostic significance of NETs and endothelial markers in SARS-CoV-2 pneumonia requires further elucidation.
Purpose of the Study:
- To evaluate the role of PMNs forming NETs and endothelial-derived parameters in patients with SARS-CoV-2 pneumonia.
- To assess the prognostic value of these markers in relation to clinical outcomes, including intensive care unit admission or death.
Main Methods:
- Prospective analysis of 87 hospitalized SARS-CoV-2 pneumonia patients and 30 healthy controls.
- Measurement of NETs, inflammatory markers (C-reactive protein, ferritin), endothelial markers (E-selectin, VCAM1, P-selectin), and D-dimer at admission, discharge, and 14 days post-discharge.
- Correlation analysis with clinical and oxygenation parameters (SpO2/FiO2 ratio).
Main Results:
- Patients with SARS-CoV-2 pneumonia exhibited higher NET formation compared to controls.
- NET formation was inversely correlated with oxygenation status (SpO2/FiO2) and positively correlated with inflammatory markers and VCAM1.
- Survivors showed a decrease, but not normalization, in NETs and endothelial markers post-discharge.
Conclusions:
- NET formation in SARS-CoV-2 pneumonia parallels inflammatory and endothelial activation markers.
- NETs are inversely related to oxygenation parameters, supporting their pathogenic role in the disease.
- Persistent elevation of NETs and endothelial markers in survivors suggests ongoing pathophysiological processes.
