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Review
. 2022 Mar:104:108516.
doi: 10.1016/j.intimp.2021.108516. Epub 2022 Jan 6.

Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality

Hayder M Al-Kuraishy  1 , Ali I Al-Gareeb  1 , Hany Akeel Al-Hussaniy  2 , Nasser A Hadi Al-Harcan  3 , Athanasios Alexiou  4 , Gaber El-Saber Batiha  5
Affiliations
Review

Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality

Hayder M Al-Kuraishy et al. Int Immunopharmacol. 2022 Mar.

Abstract

Coronavirus disease 2019 (Covid-19) is a worldwide infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). In severe SARS-CoV-2 infection, there is severe inflammatory reactions due to neutrophil recruitments and infiltration in the different organs with the formation of neutrophil extracellular traps (NETs), which involved various complications of SARS-CoV-2 infection. Therefore, the objective of the present review was to explore the potential role of NETs in the pathogenesis of SARS-CoV-2 infection and to identify the targeting drugs against NETs in Covid-19 patients. Different enzyme types are involved in the formation of NETs, such as neutrophil elastase (NE), which degrades nuclear protein and release histones, peptidyl arginine deiminase type 4 (PADA4), which releases chromosomal DNA and gasdermin D, which creates pores in the NTs cell membrane that facilitating expulsion of NT contents. Despite of the beneficial effects of NETs in controlling of invading pathogens, sustained formations of NETs during respiratory viral infections are associated with collateral tissue injury. Excessive development of NETs in SARS-CoV-2 infection is linked with the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) due to creation of the NETs-IL-1β loop. Also, aberrant NTs activation alone or through NETs formation may augment SARS-CoV-2-induced cytokine storm (CS) and macrophage activation syndrome (MAS) in patients with severe Covid-19. Furthermore, NETs formation in SARS-CoV-2 infection is associated with immuno-thrombosis and the development of ALI/ARDS. Therefore, anti-NETs therapy of natural or synthetic sources may mitigate SARS-CoV-2 infection-induced exaggerated immune response, hyperinflammation, immuno-thrombosis, and other complications.

Keywords: Acute lung injury; Acute respiratory distress syndrome; Covid-19; Cytokine storm; Immuno-thrombosis; Neutrophil extracellular traps.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Neutrophil extracellular traps in infections.
Fig. 2
Fig. 2
Generation of Neutrophil extracellular traps (adopted from Papayannopoulos 2018 .
Fig. 3
Fig. 3
Neutrophil extracellular traps and invading pathogens (adopted from Cortjens et al., 2017 [28]).
Fig. 4
Fig. 4
Neutrophil extracellular traps and Covid-19 (Adopted from Java et al., [34]).
Fig. 5
Fig. 5
Neutrophil extracellular traps and acute lung injury in Covid-19.
Fig. 6
Fig. 6
Neutrophil extracellular traps and coagulopathy in Covid-19.
Fig. 7
Fig. 7
Neutrophil extracellular traps and hypertension.
Fig. 8
Fig. 8
Different effects of activated neutrophil extracellular traps in Covid-19.
See this image and copyright information in PMC

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