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

Abstract

Severe 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.

Keywords: COVID-19; NETs; neutrophils.

FIG 1

Degradation of NETs as a risk factor for severe coinfections and damage of the lung. In the case of a severe lung infection, e.g., with SARS-CoV-2, neutrophils are activated and release NETs. The host itself produces nucleases to eliminate and recycle NET products. Importantly, nuclease-mediated degradation of NETs may promote the growth of certain bacteria that use degraded NET products as an efficient source for NAD or adenosine.