The Balance of Neutrophil Extracellular Trap Formation and Nuclease Degradation: an Unknown Role of Bacterial Coinfections in COVID-19 Patients?

Scot P. Ouellette,Maren von Köckritz-Blickwede,Nicole de Buhr

doi:10.1128/mbio.03304-20

Scot P. Ouellette, Maren von Köckritz-Blickwede

Open Access

https://doi.org/10.1128/mbio.03304-20

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Journal: mBio	Publication Date: Feb 16, 2021
Citations: 16	License type: cc-by

Affiliation: University of Veterinary Medicine Hannover, Foundation

Abstract

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to public health crises worldwide. An understanding of the pathogenesis and the development of treatment strategies is of high interest. Recently, neutrophil extracellular traps (NETs) have been identified as a potential driver of severe SARS-CoV-2 infections in humans. NETs are extracellular DNA fibers released by neutrophils after contact with various stimuli and accumulate antimicrobial substances or host defense peptides. When massively released, NETs are described to contribute to immunothrombosis in acute respiratory distress syndrome and in vascular occlusions. Based on the increasing evidence that NETs contribute to severe COVID-19 cases, DNase treatment of COVID-19 patients to degrade NETs is widely discussed as a potential therapeutic strategy. Here, we discuss potential detrimental effects of NETs and their nuclease degradation, since NET fragments can boost certain bacterial coinfections and thereby increase the severity of the disease.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to public health crises worldwide
It is of high interest that we have shown in our own recent publication that nuclease-mediated degradation of neutrophil extracellular traps (NETs) promotes the growth of certain bacteria (e.g., Actinobacillus pleuropneumoniae or Haemophilus influenzae) that use degraded NET products as an efficient source for NAD or adenosine [26]
It is considered that a therapeutic nuclease treatment might be helpful to prevent the detrimental effects of massive NET formation during COVID19

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to public health crises worldwide. Several studies have focused on DNase treatments for severe COVID-19 to degrade NETs. Based on the described NET formation in COVID-19 patients, it is logical to consider dornase alfa (Pulmozyme) for the treatment of severe COVID-19 ARDS [44].

Results

Conclusion