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Authors:Veras et al. 

Journal/ Pre-PrintmedRxiv preprint 

Tags: Immunology/immunity, inflammation, molecular biology

Research Highlights  

  1. Spontaneous NETosis in both blood circulating and infiltrated lung neutrophils. 

  1. Viable but not inactivated SARS-COV-2 induces healthy neutrophils in vitro to release NETS. 

  1. NETS released by neutrophils induce lung epithelial cell death in in vitro co-culture.  

  1. Inhibitors of NETs synthesis or promoters of NETs fragmentation may be beneficial. 

Summary

Veras et al conducted a cohort study of 32 critical and severe Covid-19 patients and found that Neutrophil Extracellular Traps (NETs) in plasma, tracheal aspirate and lung tissue at higher concentration compared to healthy controlsThe authors demonstrated spontaneous NET formation of neutrophils in blood and lung of Covid-19 patients. An interesting observation was that viable SARS-COV-2 virus was capable of inducing neutrophils to produce NETs, with viral antigens being detected inside neutrophils. These NETs could induce apoptosis of lung epithelial cells in in vitro co-cultureInhibitors of NETs synthesis or promoters of NETs fragmentation may be beneficial as part of Covid treatment.  

Impact for SARS-CoV2/COVID19 research efforts  

  • NETs contribute to COVID19 pathogenesis. 

  • The Inhibition of NET formation or promoters of NET fragmentation can be a therapeutic option of COVID19 

Study Type  

  • In vitro study 

  • In vivo study 

Methodology;

Plasma analysis of MPO-DNA complexes 

Immunostaining and confocal microscopy 

In vitro induction of NETosis with viable SARS-COV-2 virus 

Epithelial cell damage assay 

Strengths and limitations of the paper 

Novelty:   

  • Spontaneous release of NETs by neutrophils from Covid-19 patients 

  • SARS-COV-2 infect and stimulate neutrophils to release NETs and these NETs cause damage to lung tissue. 

  • Detection of SARS-COV-2 antigens in NETosing neutrophils from Covid-19 patients 

Limitations: 

  • Lack of control for controversial SARS-COV-2 antigen detection in other immune cells 

  • Only severe and critical Covid-19 patients 

Standing in the field: 

Cytotoxic effect of NET release has been demonstrated in several studies.  

Appropriate statistics: yes  

Viral model used: in vitro induction with viable SARS-COV-2 

Translatability: inhibition of NET formation by PAD4 or promotion of NET fragmentation by DNase represent potential therapeutic strategies for Covid-19.