Significance of NETs Formation in COVID-19

Janiuk, Karolina; Jabłońska, Ewa; Garley, Marzena

doi:10.3390/cells10010151

Cited by 84 publications

(90 citation statements)

References 70 publications

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“…This question has been raised in a number of previous perspective and review articles, where an approach that targets specific signalling pathways and/or neutrophil products (e.g. NETs, ROS or proteases) appears to be favoured over strategies that would result in the complete suppression of neutrophil function (36,37,137,138,191,(229)(230)(231). Indeed, given the abovementioned susceptibility of hospitalised COVID-19 patients to bacterial and fungal superinfections (175,(208)(209)(210), a therapeutic strategy that suppresses neutrophil hyperactivity whilst preserving anti-microbial function would be best placed to reduce neutrophil-mediated bystander tissue damage without increasing the risk of secondary infections (231).…”

Section: Are Neutrophils a Potential Therapeutic Target For The Treatment Of Covid-19?mentioning

confidence: 99%

Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets

Hazeldine

Lord

2021

Front. Immunol.

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Whilst the majority of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, experience mild to moderate symptoms, approximately 20% develop severe respiratory complications that may progress to acute respiratory distress syndrome, pulmonary failure and death. To date, single cell and high-throughput systems based analyses of the peripheral and pulmonary immune responses to SARS-CoV-2 suggest that a hyperactive and dysregulated immune response underpins the development of severe disease, with a prominent role assigned to neutrophils. Characterised in part by robust generation of neutrophil extracellular traps (NETs), the presence of immature, immunosuppressive and activated neutrophil subsets in the circulation, and neutrophilic infiltrates in the lung, a granulocytic signature is emerging as a defining feature of severe COVID-19. Furthermore, an assessment of the number, maturity status and/or function of circulating neutrophils at the time of hospital admission has shown promise as a prognostic tool for the early identification of patients at risk of clinical deterioration. Here, by summarising the results of studies that have examined the peripheral and pulmonary immune response to SARS-CoV-2, we provide a comprehensive overview of the changes that occur in the composition, phenotype and function of the neutrophil pool in COVID-19 patients of differing disease severities and discuss potential mediators of SARS-CoV-2-induced neutrophil dysfunction. With few specific treatments currently approved for COVID-19, we conclude the review by discussing whether neutrophils represent a potential therapeutic target for the treatment of patients with severe COVID-19.

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Section: Are Neutrophils a Potential Therapeutic Target For The Treatment Of Covid-19?mentioning

confidence: 99%

Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets

Hazeldine

Lord

2021

Front. Immunol.

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“…There are two molecules related to NETs that are associated with the severity of SARS-CoV-2 lung infection; cell-free DNA and MPO-DNA have been found to be elevated in patients with the severe form of the disease [ 109 , 110 ]. On the other hand, Cit-H3, a main component of NETs, has been found to be increased in both forms of the disease with no significant difference [ 111 , 112 , 113 ].…”

Section: Biomolecules and Cellular Elements Involved In The Interaction With Netsmentioning

confidence: 99%

Immunothrombosis in COVID-19: Implications of Neutrophil Extracellular Traps

et al. 2021

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SARS-CoV-2 is a member of the family of coronaviruses associated with severe outbreaks of respiratory diseases in recent decades and is the causative agent of the COVID-19 pandemic. The recognition by and activation of the innate immune response recruits neutrophils, which, through their different mechanisms of action, form extracellular neutrophil traps, playing a role in infection control and trapping viral, bacterial, and fungal etiological agents. However, in patients with COVID-19, activation at the vascular level, combined with other cells and inflammatory mediators, leads to thrombotic events and disseminated intravascular coagulation, thus leading to a series of clinical manifestations in cerebrovascular, cardiac, pulmonary, and kidney disease while promoting severe disease and mortality. Previous studies of hospitalized patients with COVID-19 have shown that elevated levels of markers specific for NETs, such as free DNA, MPO, and H3Cit, are strongly associated with the total neutrophil count; with acute phase reactants that include CRP, D-dimer, lactate dehydrogenase, and interleukin secretion; and with an increased risk of severe COVID-19. This study analyzed the interactions between NETs and the activation pathways involved in immunothrombotic processes in patients with COVID-19.

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“…116 Evidence suggests that COVID-19 leads to excessive production of neutrophil extracellular traps (NETs) (NETosis), especially in patients with severe disease, which is a key mechanism that predisposes to untoward effects including thromboembolic complications and damage to surrounding tissues and organs. 117 COVID-19 microthrombus formation seems to be more closely related to endothelial damage and complement-mediated thrombotic microangiopathy, rather than sepsis-induced coagulopathy or disseminated intravascular coagulation (DIC). 118 Acute cardiac injury in COVID-19 may be due to virusmediated lysis of myocardial cells, also observed in other viral infections, or as a consequence of COVID-binding ACE2 receptors in the heart, thus reducing the activity of ACE2 and dampening the cardioprotective effects of this enzyme.…”

Section: Acute Cardiac Injurymentioning

confidence: 99%

COVID-19 and Acute Myocardial Injury and Infarction: Related Mechanisms and Emerging Challenges

Manolis¹,

Manolis

et al. 2021

J Cardiovasc Pharmacol Ther

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In the era of the coronavirus disease 2019 (COVID-19) pandemic, acute cardiac injury (ACI), as reflected by elevated cardiac troponin above the 99th percentile, has been observed in 8%-62% of patients with COVID-19 infection with highest incidence and mortality recorded in patients with severe infection. Apart from the clinically and electrocardiographically discernible causes of ACI, such as acute myocardial infarction (MI), other cardiac causes need to be considered such as myocarditis, Takotsubo syndrome, and direct injury from COVID-19, together with noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis. Acute coronary syndromes (ACS) with normal or near-normal coronary arteries (ACS-NNOCA) appear to have a higher prevalence in both COVID-19 positive and negative patients in the pandemic compared to the pre-pandemic era. Echocardiography, coronary angiography, chest computed tomography and/or cardiac magnetic resonance imaging may render a correct diagnosis, obviating the need for endomyocardial biopsy. Importantly, a significant delay has been recorded in patients with ACS seeking advice for their symptoms, while their routine care has been sharply disrupted with fewer urgent coronary angiographies and/or primary percutaneous coronary interventions performed in the case of ST-elevation MI (STEMI) with an inappropriate shift toward thrombolysis, all contributing to a higher complication rate in these patients. Thus, new challenges have emerged in rendering a diagnosis and delivering treatment in patients with ACI/ACS in the pandemic era. These issues, the various mechanisms involved in the development of ACI/ACS, and relevant current guidelines are herein reviewed.

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Significance of NETs Formation in COVID-19

Cited by 84 publications

References 70 publications

Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets

Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets

Immunothrombosis in COVID-19: Implications of Neutrophil Extracellular Traps

COVID-19 and Acute Myocardial Injury and Infarction: Related Mechanisms and Emerging Challenges

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