Association of Neutrophil Activation, More Than Platelet Activation, With Thrombotic Complications in Coronavirus Disease 2019

Petito, Eleonora; Falcinelli, Emanuela; Paliani, Ugo; Césari, E.; Vaudo, Gaetano; Sebastiano, Manuela; Cerotto, Vittorio; Guglielmini, Giuseppe; Gori, Francesca; Malvestiti, Marco; Becattini, Cecilia; Paciullo, Francesco; Robertis, Edoardo De; Bury, Loredana; Lazzarini, Teseo; Gresele, Paolo; Lapenna, Maria; D’Abbondanza, Marco; Cristallini, Stefano; Franco, Laura; Saccarelli, Luca

doi:10.1093/infdis/jiaa756

Cited by 127 publications

(193 citation statements)

References 49 publications

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“…These observations implicate neutrophils as potential perpetuators of inflammation and respiratory compromise in COVID-19 [84]. Moreover, patients with COVID-19-associated thrombosis had significantly higher blood levels of NETs and neutrophil activation markers such as CLP compared with COVID-19 patients without thrombosis [85]. Additionally, many studies support that fecal CLP indicates intestinal inflammation in COVID-19 [86][87][88].…”

Section: Clp In Respiratory Infectionsmentioning

confidence: 91%

Calprotectin in Lung Diseases

Kotsiou

Papagiannis

Papadopoulou

et al. 2021

IJMS

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Calprotectin (CLP) is a heterodimer formed by two S-100 calcium-binding cytosolic proteins, S100A8 and S100A9. It is a multifunctional protein expressed mainly by neutrophils and released extracellularly by activated or damaged cells mediating a broad range of physiological and pathological responses. It has been more than 20 years since the implication of S100A8/A9 in the inflammatory process was shown; however, the evaluation of its role in the pathogenesis of respiratory diseases or its usefulness as a biomarker for the appropriate diagnosis and prognosis of lung diseases have only gained attention in recent years. This review aimed to provide current knowledge regarding the potential role of CLP in the pathophysiology of lung diseases and describe how this knowledge is, up until now, translated into daily clinical practice. CLP is involved in numerous cellular processes in lung health and disease. In addition to its anti-microbial functions, CLP also serves as a molecule with pro- and anti-tumor properties related to cell survival and growth, angiogenesis, DNA damage response, and the remodeling of the extracellular matrix. The findings of this review potentially introduce CLP in daily clinical practice within the spectrum of respiratory diseases.

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Section: Clp In Respiratory Infectionsmentioning

confidence: 91%

Calprotectin in Lung Diseases

Kotsiou

Papagiannis

Papadopoulou

et al. 2021

IJMS

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“…The NET-remnants, including circulating cell-free DNA, citrullinated H3, or MPO-DNA complexes, are abundantly found in the circulation of patients with severe COVID-19 [ 52 , 93 ]. Furthermore, neutrophil-platelet aggregates and neutrophil activation markers are also increased in patients with severe disease [ 65 , 94 ]. Importantly, NETs from patients with COVID-19 are loaded with tissue factor (TF).…”

Section: Nets’ Impact At the Cellular Levelmentioning

confidence: 99%

Patients with COVID-19: in the dark-NETs of neutrophils

et al. 2021

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SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.

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“…ACE2 induces vasodilatory activity through Ang-(1-7) and the Mas receptor. This is the reason a decrease in ACE2 activity connected with the penetration of the cell by SARS-CoV-2 causes vessel contraction leading to hypertension [41,43,[48][49][50]. The later infiltration of neutrophils and their degranulation and the release of NETs contributes to excessive inflammatory response and progression of diseases affecting the circulatory system [51,52].…”

Section: Nets and Covid-19 Progression In People With Concurrent Diseasesmentioning

confidence: 99%

Significance of NETs Formation in COVID-19

Janiuk

Jabłońska

Garley

2021

Cells

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Severe contagious respiratory disease—COVID-19—caused by the SARS-CoV-2 coronavirus, can lead to fatal respiratory failure associated with an excessive inflammatory response. Infiltration and spread of SARS-CoV-2 are based on the interaction between the virus’ structural protein S and the cell’s receptor–angiotensin-converting enzyme 2 (ACE2), with the simultaneous involvement of human trans-membrane protease, serine 2 (TMPRSS2). Many scientific reports stress the importance of elevated recruitment and activity of neutrophils, which can form extracellular neutrophil traps (NETs) playing a significant role in the mechanism of combating pathogens, in the pathogenesis of COVID-19. Excessive generation of NETs during prolonged periods of inflammation predisposes for the occurrence of undesirable reactions including thromboembolic complications and damage to surrounding tissues and organs. Within the present manuscript, we draw attention to the impact of NET generation on the severe course of COVID-19 in patients with concurrent cardiovascular and metabolic diseases. Additionally, we indicate the necessity to explore not only the cellular but also the molecular bases of COVID-19 pathogenesis, which may aid the development of dedicated therapies meant to improve chances for the successful treatment of patients. We also present new directions of research into medications that display NETs formation regulatory properties as potential significant therapeutic strategies in the progress of COVID-19.

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Association of Neutrophil Activation, More Than Platelet Activation, With Thrombotic Complications in Coronavirus Disease 2019

Cited by 127 publications

References 49 publications

Calprotectin in Lung Diseases

Calprotectin in Lung Diseases

Patients with COVID-19: in the dark-NETs of neutrophils

Significance of NETs Formation in COVID-19

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