NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Март 2, 2022

Infection with SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19) pandemic, causes respiratory problems and multifaceted organ dysfunction. A crucial mechanism COVID-19 immunopathy is recruitment activation neutrophils at infection site, which also predicts severity poor outcomes. The release neutrophil extracellular traps (NETs), occurring during a regulated form cell death known as NETosis, key effector function that mediates harmful effects caused by neutrophils. Abundant NETosis NET generation have been observed in many patients, leading to unfavorable coagulopathy immunothrombosis. Moreover, excessive are now more widely recognized mediators additional pathophysiological abnormalities following SARS-CoV-2 infection. In this minireview, we introduce subtypes NET-producing (e.g., low-density granulocytes) explain biological importance NETs protein cargos COVID-19. addition, discuss mechanisms upregulating viral processes entry replication) well host pro-NET proinflammatory mediator release, platelet activation, autoantibody production). Furthermore, provide an update main findings immunothrombosis other COVID-19-related disorders, such aberrant immunity, neurological post syndromes including lung fibrosis, disorder, tumor progression, deteriorated chronic illness. Finally, address potential prospective treatment strategies target dysregulated formation via inhibition promotion degradation, respectively.

Язык: Английский

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Hyperinflammatory Immune Response and COVID-19: A Double Edged Sword

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Сен. 30, 2021

The coronavirus disease-19 (COVID-19) elicited by the severe acute respiratory syndrome 2 (SARS-CoV-2) has caused devastating health, economic and social impact worldwide. Its clinical spectrum ranges from asymptomatic to failure multi-organ or death. pathogenesis of SARS-CoV-2 infection is attributed a complex interplay between virus host immune response. It involves activation multiple inflammatory pathways leading hyperinflammation cytokine storm, resulting in tissue damage, distress (ARDS) failure. Accumulating evidence raised concern over long-term health effects COVID-19. Importantly, neuroinvasive potential may have consequences brain. This review provides conceptual framework on how tricks system induce cause disease. We also explore key differences mild COVID-19 its short- effects, particularly human

Язык: Английский

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Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4896 - 4896

Опубликована: Март 3, 2023

Although many studies have been exploring the mechanisms driving NETs formation, much less attention has paid to degradation and elimination of these structures. The clearance effective removal extracellular DNA, enzymatic proteins (neutrophil elastase, proteinase 3, myeloperoxidase) or histones are necessary maintain tissue homeostasis, prevent inflammation avoid presentation self-antigens. persistence overabundance DNA fibers in circulation tissues may dramatic consequences for a host leading development various systemic local damage. cleaved by concerted action secreted deoxyribonucleases (DNases) followed intracellular macrophages. accumulation depends on ability DNase I DNAse II hydrolyze DNA. Furthermore, macrophages actively engulf this event is facilitated preprocessing I. purpose review present discuss current knowledge about its role pathogenesis thrombosis, autoimmune diseases, cancer severe infections, as well possibilities potential therapeutic interventions. Several anti-NETs approaches had effects animal models diseases; nevertheless, new drugs patients needs further study an clinical compounds that able target NETs.

Язык: Английский

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The role of neutrophil extracellular traps in sepsis and sepsis-related acute lung injury

International Immunopharmacology, Год журнала: 2023, Номер 124, С. 110436 - 110436

Опубликована: Сен. 7, 2023

Язык: Английский

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RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections

PLoS ONE, Год журнала: 2022, Номер 17(1), С. e0261679 - e0261679

Опубликована: Янв. 26, 2022

Infection with the SARS-CoV2 virus can vary from asymptomatic, or flu-like moderate disease, up to critically severe. Severe termed COVID-19, involves acute respiratory deterioration that is frequently fatal. To understand highly variable presentation, and identify biomarkers for disease severity, blood RNA COVID-19 patient in an intensive care unit was analyzed by whole transcriptome sequencing. Both infection severity of syndrome were associated 25-fold increased expression neutrophil-related transcripts, such as neutrophil defensin 1 (DEFA1), 3-5-fold reductions T cell related transcripts receptor (TCR). The DEFA1 level detected viremia 95.5% sensitivity, when measured ddPCR RNA. Purified CD15+ neutrophils patients abundance showed striking increases nuclear DNA staining DAPI. Concurrently, they >10-fold higher elastase activity than normal controls, correcting their abundance, still 5-fold per cell. Despite activity, extremely low plasma same patients. Collectively, data supports model decreased suggests levels both involved extracellular traps (NETs), may be informative host immune after viral infection.

Язык: Английский

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Post-COVID-19 syndrome mechanisms, prevention and management

International Journal of Preventive Medicine, Год журнала: 2023, Номер 14(1)

Опубликована: Май 1, 2023

As the population of patients recovering from COVID-19 grows, post challenges are recognizing by ongoing evidences at once. Long COVID is defined as a syndrome with range persistent symptoms that remain long after (beyond 12 weeks) acute SARS-CoV-2 infection. Studies have shown can cause multi-organ damages wide spectrum manifestations. Many systems, but not limited to, including respiratory, cardiovascular, nervous, gastrointestinal, and musculoskeletal involved in COVID. Fatigue dyspnea most common may be driven tissue damage caused virus-specific pathophysiologic changes or secondary to pathological long-lasting inflammatory response because viral persistence, immune dysregulation, autoimmune reactions. Some risk factors like sex age, more than five early symptoms, specific biomarkers been revealed probable predicator discussed this review. It seems vaccination only way for prevention it also help who had already Managing survivors recommended being multidisciplinary approach, framework identifying those high post-acute must proposed. Possible therapeutic options useful investigation tools follow-up suggested In sum, evidence researches regularly updated, we provide current understanding epidemiology, clinical manifestation, suspected pathophysiology, associated factors, treatment

Язык: Английский

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Roles of host proteases in the entry of SARS-CoV-2

Animal Diseases, Год журнала: 2023, Номер 3(1)

Опубликована: Апрель 25, 2023

Abstract The spike protein (S) of SARS-CoV-2 is responsible for viral attachment and entry, thus a major factor host susceptibility, tissue tropism, virulence pathogenicity. S divided with S1 S2 region, the contains receptor-binding domain (RBD), while hydrophobic fusion entry into cell. Numerous proteases have been implicated in activation through various cleavage sites. In this article, we review including furin, trypsin, transmembrane protease serine 2 (TMPRSS2) cathepsins S. Many betacoronaviruses polybasic residues at S1/S2 site which subjected to by furin. facilitates more assessable RBD receptor ACE2, binding triggers further conformational changes exposure S2’ such as type II (TTPRs) TMPRSS2. presence TMPRSS2 on target cells, can utilize direct route envelope cellular membrane. absence TMPRSS2, enter cells via endosomes where multiple cleave successful entry. Additional involved were discussed. This article also includes roles 3C-like inhibitors inhibitory activity against cathepsin L SARS-CoV-2, discussed dual virus replication.

Язык: Английский

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Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 12, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a contagious virus that the cause of disease 2019 (COVID-19) pandemic which has posed serious threat to public health. COVID-19 characterized by wide spectrum clinical manifestations, ranging from asymptomatic infection mild cold-like symptoms, severe pneumonia or even death. Inflammasomes are supramolecular signaling platforms assemble in response danger microbial signals. Upon activation, inflammasomes mediate innate immune defense favoring release proinflammatory cytokines and triggering pyroptotic cell Nevertheless, abnormalities inflammasome functioning can result variety human diseases such as autoimmune disorders cancer. A growing body evidence showed SARS-CoV-2 induce assembly. Dysregulated activation consequent cytokine burst have been associated with severity, alluding implication pathophysiology. Accordingly, an improved understanding inflammasome-mediated inflammatory cascades essential uncover immunological mechanisms pathology identify effective therapeutic approaches for this devastating disease. In review, we summarize most recent findings on interplay between contribution activated progression. We dissect involving machinery immunopathogenesis. addition, provide overview inflammasome-targeted therapies antagonists potential utility treatment.

Язык: Английский

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COVID-19: Not a thrombotic disease but a thromboinflammatory disease

Upsala Journal of Medical Sciences, Год журнала: 2024, Номер 129

Опубликована: Янв. 22, 2024

While Coronavirus Disease in 2019 (COVID-19) may no longer be classified as a global public health emergency, it still poses significant risk at least due to its association with thrombotic events. This study aims reaffirm our previous hypothesis that COVID-19 is fundamentally disease. To accomplish this, we have undertaken an extensive literature review focused on assessing the comprehensive impact of entire hemostatic system. Our analysis revealed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection significantly enhances initiation thrombin generation. However, noteworthy generation modulated by specific anticoagulants present patients’ plasma. Consequently, higher levels fibrinogen appear play more pivotal role promoting coagulation COVID-19, opposed Furthermore, viral can stimulate platelet activation either through widespread dissemination from lungs other organs or localized effects platelets themselves. An imbalance between Von Willebrand Factor (VWF) and ADAMTS-13 also contributes exaggerated response this disease, addition elevated D-dimer levels, coupled increase fibrin viscoelasticity. paradoxical phenotype has been identified ‘fibrinolysis shutdown’. clarify pathogenesis underlying these disorders examined published data, tracing reaction process relevant proteins cells, ACE2-dependent invasion, induced tissue inflammation, endothelial injury, innate immune responses, occurrence We therefrom understand should viewed disease solely based abnormalities clot formation proteolysis. Instead, regarded thromboinflammatory disorder, incorporating both classical elements cellular inflammation their intricate interactions coagulopathy.

Язык: Английский

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A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1464 - 1464

Опубликована: Янв. 25, 2024

Nowadays, acute respiratory distress syndrome (ARDS) still has a high mortality rate, and the alleviation treatment of ARDS remains major research focus. There are various causes ARDS, among which pneumonia non-pulmonary sepsis most common. Trauma blood transfusion can also cause ARDS. In aggregation infiltration neutrophils in lungs have great influence on development disease. Neutrophils regulate inflammatory responses through pathways, release neutrophil extracellular traps (NETs) is considered to be one important mechanisms. NETs mainly composed DNA, histones, granuloproteins, all mediate downstream signaling pathways that activate responses, generate immune clots, damage surrounding tissues. At same time, components promote formation NETs, thus forming vicious cycle continuously aggravates progression associated with cytokine storms balance. Since DNA main component DNase I viable drug for removing NETs. Other therapeutic methods inhibit worthy further exploration. This review discusses mechanism Understanding association between may help develop new perspectives

Язык: Английский

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