Neutrophil Extracellular Traps (NETs): importance in pathogenesis and potential therapeutic target in COVID-19

  • Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP)
  • Total publications:5 publications

Grant number: 2020/05601-6

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2022
  • Known Financial Commitments (USD)

    $70,925.21
  • Funder

    Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP)
  • Principle Investigator

    Pending
  • Research Location

    Brazil, Americas
  • Lead Research Institution

    Universidade de São Paulo
  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Pathogen morphology, shedding & natural history

  • Special Interest Tags

    Gender

  • Study Subject

    Clinical

  • Clinical Trial Details

    Unspecified

  • Broad Policy Alignment

    Pending

  • Age Group

    Unspecified

  • Vulnerable Population

    Unspecified

  • Occupations of Interest

    Unspecified

Abstract

2019 coronavirus disease (Covid19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has become a major health problem worldwide. The pulmonary changes observed in patients with Covid-19 are characterized by intense damage to epithelial and endothelial cells, viral replication in lung tissue and extensive inflammatory process characterized by edema, infiltration of inflammatory cells, including neutrophils and increased tissue concentrations of inflammatory cytokines , such as TNF- ±, IL-1 and IL-6. In addition to pulmonary changes, there is also a systemic inflammatory response with important lesions in other organs such as kidneys, heart and intestines. Recent studies suggest that neutrophils participate in lung injuries and possibly in other organs, but it is not yet clear what mechanisms are involved. Among the cytotoxic mediators released by this cell type are free radicals, enzymes and NETs (from Neutrophil Extracellular Traps) or, simply, extracellular traps of neutrophils, which are networks of DNA conjugated with antimicrobial enzymes such as myeloperoxidase (MPO), elastase and citrullinated histones. NETs are described as one of the main mediators responsible for injuries seen in several autoimmune diseases and also in vital organs during sepsis. However, the involvement of NETs in the injuries observed at Covid-19 remains unknown. Therefore, the objective of the present project is to identify the participation of NETs in the pathogenesis of Covid-19. The possible involvement of NETs in the pathogenesis of Covid-19 will allow us to propose new therapeutic approaches for this disease, that is, drugs that degrade this mediator and / or inhibit its synthesis. In this sense, we are also proposing to conduct an open clinical trial treating patients with Covid-19 with Pulmozyme. Pulmozyme is used in the clinic to treat cystic fibrosis and its active ingredient is DNAs that degrade NETs. Confirming the feasibility of the project, in a preliminary experiment, we observed an exacerbated production of NETs by isolated neutrophils and in the plasma of patients affected with Covid-19.

Publicationslinked via Europe PMC

Last Updated:37 minutes ago

View all publications at Europe PMC

Neutrophil Virucidal Activity Against SARS-CoV-2 Is Mediated by Neutrophil Extracellular Traps.

Enoxaparin improves COVID-19 by reducing Neutrophils Extracellular Traps (NETs) production.

NET-targeted therapy: effects, limitations, and potential strategies to enhance treatment efficacy.

Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial.

SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology.