Neutrophils and COVID-19: Nots, NETs, and knots

Nathan, Carl

doi:10.1084/jem.20201439

Cited by 47 publications

(48 citation statements)

References 16 publications

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“…NETs consist of neutrophil-extruded DNA coated with histones, neutrophil elastase (NE), and myeloperoxidase (MPO). Peptidylarginine deiminase 4 (PAD4), NE, and gasdermin D along with free DNA, all participate in the NET formation ( Nathan, 2020 ). NETs are prevalent in blood, trachea, and lung specimens of COVID-19 patients ( Veras et al, 2020 ).…”

Section: Targeting Neutrophils May Improve the Treatment Of Ards Causmentioning

confidence: 99%

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

et al. 2020

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This review describes targeting neutrophils as a potential therapeutic strategy for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19), a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutrophil counts are significantly elevated in patients with COVID-19 and significantly correlated with disease severity. The neutrophil-to-lymphocyte ratio can serve as a clinical marker for predicting fatal complications related to ARDS in patients with COVID-19. Neutrophil-associated inflammation plays a critical pathogenic role in ARDS. The effector functions of neutrophils, acting as respiratory burst oxidants, granule proteases, and neutrophil extracellular traps, are linked to the pathogenesis of ARDS. Hence, neutrophils can not only be used as pathogenic markers but also as candidate drug targets for COVID-19 associated ARDS.

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Section: Targeting Neutrophils May Improve the Treatment Of Ards Causmentioning

confidence: 99%

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

et al. 2020

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“…Mounting evidence points to a hyper-reactive and dysregulated inflammatory response characterized by overexpression of pro-inflammatory cytokines (cytokine storm) and severe immunopathology as specific presentations in severe COVID-19 [2][3][4][5][6]. An over-exuberant innate immune response with larger numbers of infiltrating neutrophils [7,8] arrests the adaptive immune response through the excessive release of reactive oxygen species that leads to extensive tissue damage and depletion of epithelial cells [9]. In addition, lymphopenia, in particular, is one of the most prominent markers of COVID-19 and has been observed in over 80% of patients [6,[10][11][12].…”

Section: Introductionmentioning

confidence: 99%

COVID-19 virtual patient cohort reveals immune mechanisms driving disease outcomes

Jenner

Aogo

Alfonso

et al. 2021

Preprint

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To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results indicate that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8+ T cell depletion. Our analyses predicted that individuals with severe COVID-19 also have accelerated monocyte-to-macrophage differentiation that was mediated by increased IL-6 and reduced type I IFN signalling. Together, these findings identify biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.Author summaryUnderstanding of how the immune system responds to SARS-CoV-2 infections is critical for improving diagnostic and treatment approaches. Identifying which immune mechanisms lead to divergent outcomes can be clinically difficult, and experimental models and longitudinal data are only beginning to emerge. In response, we developed a mechanistic, mathematical and computational model of the immunopathology of COVID-19 calibrated to and validated against a broad set of experimental and clinical immunological data. To study the drivers of severe COVID-19, we used our model to expand a cohort of virtual patients, each with realistic disease dynamics. Our results identify key processes that regulate the immune response to SARS-CoV-2 infection in virtual patients and suggest viable therapeutic targets, underlining the importance of a rational approach to studying novel pathogens using intra-host models.

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“…The evidence for the presence of NETs (and etosis) in Covid-19 are limited, however it is likely that more findings on NETs could be reported in the near future since the pandemic still goes on. NETs contributing immunothrombosis are responsible for clinical presentations in patients with severe Covid-19 and may represent a potential target for severity biomarker and/ or therapeutic intervention [39].…”

Section: Potential Contribution Of Extracellular Traps In Covid-19mentioning

confidence: 99%

Potential Roles of Extracellular Traps in the Progression of Coronavirus Disease (Covid)-19

Pertiwi¹

2021

Advances in Social Science, Education and Humanities Research

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Millions of people have suffered from coronavirus disease (COVID)-19 worldwide with diverse clinical presentations, ranging from asymptomatic to severe pneumonia leading to respiratory failure and even death. In critical phases, thrombosis and inflammation are considered as the important contributors in the processes. Extracellular traps (ETs), meshes-like chromatin DNA decorated with antimicrobial proteins, have become interesting features in immunothrombosis research due to their pro-inflammatory, pro-thrombotic and pro-coagulant properties. These traps, released by innate inflammatory cells, mark a distinct form of cell death namely etosis. Whether etosis may also participate in the thrombotic inflammation of Covid-19 progression and whether the roles are beneficial or detrimental are still not much known. This review presents current knowledge on the formation, properties and roles of ETs in human non-infectious diseases, particularly in inflammation, thrombosis and coagulopathy, followed by an exploration on how SARS-CoV2 may trigger the formation of ETs. Next, the pathogenesis of Covid-19 is briefly discussed, gathering current findings on the involvement of ETs in the immunopathological mechanisms during Covid-19 infection. Lastly, this review discusses the potential roles of etosis in the progression of Covid-19, thereby targeting the extracellular traps as a severity biomarker and/or a therapeutic approach in the management of Covid-19.

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Neutrophils and COVID-19: Nots, NETs, and knots

Abstract: The pace of the COVID-19 pandemic makes it timely to take stock of evidence for the involvement of neutrophils and NETs, to weigh the implications, and to increase efficiency in clinical trials.

Cited by 47 publications

References 16 publications

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

COVID-19 virtual patient cohort reveals immune mechanisms driving disease outcomes

Potential Roles of Extracellular Traps in the Progression of Coronavirus Disease (Covid)-19

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