The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19)

Angélica Arcanjo,Alexandre Morrot,Debora Decoté-Ricardo,Mirella Carneiro Dos Reis,Christina Takiya,Leonardo Freire-De-Lima,Adriane Regina Todeschini,Celio Geraldo Freire-De-Lima,Yasmin Da Silva Fontes,Jorgete Logullo,Wilson Savino,Camilla Cristie Barreto Menezes,Shana Priscila Coutinho Barroso,Antônio Ferreira-Pereira,Thais Chrispim De Souza Carvalho Giangiarulo,Fátima Conceição-Silva,Gabriellen Menezes Migliani De Castro

doi:10.1038/s41598-020-76781-0

Abstract

The novel coronavirus SARS-CoV-2 causes COVID-19, a highly pathogenic viral infection threatening millions. The majority of the individuals infected are asymptomatic or mildly symptomatic showing typical clinical signs of common cold. However, approximately 20% of the patients can progress to acute respiratory distress syndrome (ARDS), evolving to death in about 5% of cases. Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for virus entry into host target cells. The upregulation of ACE2 in patients with comorbidities may represent a propensity for increased viral load and spreading of infection to extrapulmonary tissues. This systemic infection is associated with higher neutrophil to lymphocyte ratio in infected tissues and high levels of pro-inflammatory cytokines leading to an extensive microthrombus formation with multiorgan failure. Herein we investigated whether SARS-CoV-2 can stimulate extracellular neutrophils traps (NETs) in a process called NETosis. We demonstrated for the first time that SARS-CoV-2 in fact is able to activate NETosis in human neutrophils. Our findings indicated that this process is associated with increased levels of intracellular Reactive Oxygen Species (ROS) in neutrophils. The ROS-NET pathway plays a role in thrombosis formation and our study suggest the importance of this target for therapy approaches against disease.

Highlights

The novel coronavirus Severe Acute Respiratory Syndrome (SARS)-CoV-2 causes COVID-19, a highly pathogenic viral infection threatening millions
We sought to investigate whether SARS-CoV-2 virus could activate neutrophils to induce NETosis
There is no evidence that viruses can use neutrophils to establish productive infections, many viruses can be detected within neutrophils, being even able to activate neutrophils to produce neutrophils traps (NETs)

Summary

Introduction

The novel coronavirus SARS-CoV-2 causes COVID-19, a highly pathogenic viral infection threatening millions. The upregulation of ACE2 in patients with comorbidities may represent a propensity for increased viral load and spreading of infection to extrapulmonary tissues This systemic infection is associated with higher neutrophil to lymphocyte ratio in infected tissues and high levels of pro-inflammatory cytokines leading to an extensive microthrombus formation with multiorgan failure. The disease has been revealed as a systemic disease, the increased expression of ACE2 in patients with comorbidities may represent a propensity for an increased viral load of infection and the spread of the virus to extrapulmonary tissues[4,5,6] This systemic virus dissemination brings complications to different organs in patients who evolve for the severe clinical form, which may affect central nervous system, eyes, heart and gut, leading to multi-organ dysfunction and extensive microthrombus formation with multiorgan failure[7]. Evidence has shown that patients recovering from SARS-CoV-2 infection show signs of antiviral T and B cell adaptive immunity, with clonal expansion and activation[8]

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Results

Conclusion