Neutrophilic extracellular traps and association with serious pulmonary complications at Covid-19
DOI:
https://doi.org/10.21527/2176-7114.2023.47.12993Keywords:
NETs; COVID-19; Coronavirus; Lung Injury.Abstract
The present study aims to define an association between the formation of NETs and the development of pulmonary disorders in Covid-19, as well as to explore its performance as a biomarker in the disease. This is an integrative literature review, through the survey of scientific articles in the following databases: PubMed, Latin American and Caribbean Literature in Health Sciences (Lilacs) and Online Medical Literature Analysis and Recovery System (Medline) Based on the inclusion and exclusion criteria, 18 articles were selected for this review. Activation of neutrophils and formation of NETs have been defined as risk factors for mortality in Covid-19 patients. The release of NETs is fully correlated with the severity of the pulmonary pathology. Throughout this study, it is concluded that the formation of excess NETs is present in severe cases of COVID-19 and associated as a biomarker of several complications such as thrombosis and coagulopathies.
References
Hu B, Guo H, Zhou P, Shi Z-L. Characteristics of SARS-CoV-2 and COVID-19. Nature Reviews Microbiology [Internet]. 2020 Oct. 6;19:1-14. Disponível em: https://www.nature.com/articles/s41579-020-00459-7#citeas
World Health Organization. WHO COVID-19 dashboard [Internet]. World Health Organization; 2021 [cited 2021 Nov. 28]. Disponível em: https://covid19.who.int/
Yaqinuddin A, Kvietys P, Kashir J. COVID-19: Role of neutrophil extracellular traps in acute lung injury. Respiratory Investigation. 2020 Sept.;58(5):419-420.
Radermecker C, Detrembleur N, Guiot J, Cavalier E, Henket M, d’Emal C, et al. Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19. Journal of Experimental Medicine [Internet]. 2020 Sept. 14 [cited 2021 Nov. 28];217(12). Disponível em: https://rupress.org/jem/article/217/12/e20201012/152084/Neutrophil-extracellular-traps-infiltrate-the-lung
Brandão SCS, Godoi ETAM, Ramos J de OX, Melo LMMP de, Sarinho ESC. COVID-19 grave: entenda o papel da imunidade, do endotélio e da coagulação na prática clínica. Jornal Vascular Brasileiro [Internet]. 2020;19. Disponível em: https://www.scielo.br/pdf/jvb/v19/1677-5449-jvb-19-e20200131.pdf
Niedźwiedzka-Rystwej P, Grywalska E, Hrynkiewicz R, Bębnowska D, Wołącewicz M, Majchrzak A, et al. Interplay between Neutrophils, NETs and T-Cells in SARS-CoV-2 Infection – A Missing Piece of the Puzzle in the COVID-19 Pathogenesis? Cells [Internet]. 2021 July 1 [cited 2021 Nov. 28];10(7):1817. Disponível em: https://www.mdpi.com/2073-4409/10/7/1817
Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine & Growth Factor Reviews. 2020 Aug;54:62-75.
Papayannopoulos V. Neutrophil extracellular traps in immunity and disease. Nature Reviews Immunology [Internet]. 2017 Oct. 9 [cited 2019 Feb. 28];18(2):134-147. Disponível em: https://www.nature.com/articles/nri.2017.105
Sollberger G, Tilley DO, Zychlinsky A. Neutrophil Extracellular Traps: The Biology of Chromatin Externalization. Developmental Cell. 2018 Mar;44(5):542-553.
Szturmowicz M, Demkow U. Neutrophil Extracellular Traps (NETs) in Severe SARS-CoV-2 Lung Disease. International Journal of Molecular Sciences. 2021 Aug. 17;22(16):8854.
Silva de Sordi LH, Sales Oliveira Magalhães I, Abreu Casselhas D, Chaves Andrade M. O Papel da Imunidade Inata na COVID-19. Revista Ciências em Saúde. 2020 July 2;10(3):5-8.
Kaplan MJ, Radic M. Neutrophil Extracellular Traps: Double-Edged Swords of Innate Immunity. The Journal of Immunology [Internet]. 2012 Sep. 6 [cited 2019 Feb. 28];189(6):2689-2.695. Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439169/
Boeltz S, Amini P, Anders H-J, Andrade F, Bilyy R, Chatfield S, et al. To NET or not to NET: current opinions and state of the science regarding the formation of neutrophil extracellular traps. Cell Death & Differentiation [Internet]. 2019 Mar. 1 [cited 2021 Nov. 28];26(3):395-408. Disponível em: https://www.nature.com/articles/s41418-018-0261-x
Thierry AR, Roch B. Neutrophil Extracellular Traps and By-Products Play a Key Role in COVID-19: Pathogenesis, Risk Factors, and Therapy. Journal of Clinical Medicine. 2020 Sep. 11;9(9):2942.
Wang J, Li Q, Yin Y, Zhang Y, Cao Y, Lin X, et al. Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19. Frontiers in Immunology. 2020 Aug. 18;11.
Gustine JN, Jones D. Immunopathology of Hyperinflammation in COVID-19. The American Journal of Pathology. 2020 Sep.
Colling ME, Kanthi Y. COVID-19-associated coagulopathy: An exploration of mechanisms. Vascular Medicine. 2020 Jun. 19;1358863X2093264
Yaqinuddin A, Kashir J. Novel therapeutic targets for SARS-CoV-2-induced acute lung injury: Targeting a potential IL-1β/neutrophil extracellular traps feedback loop. Medical Hypotheses. 2020 Oct.;143:109906.
Chen X, Guo H, Qiu L, Zhang C, Deng Q, Leng Q. Immunomodulatory and Antiviral Activity of Metformin and Its Potential Implications in Treating Coronavirus Disease 2019 and Lung Injury. Frontiers in Immunology. 2020 Aug. 18;11.
Borczuk AC. Pulmonary pathology of COVID-19. Current Opinion in Pulmonary Medicine. 2021 Jan. 4; Publish Ahead of Print.
Lasky JA, Fuloria J, Morrison ME, Lanier R, Naderer O, Brundage T, et al. Design and Rationale of a Randomized, Double-Blind, Placebo-Controlled, Phase 2/3 Study Evaluating Dociparstat in Acute Lung Injury Associated with Severe COVID-19. Advances in Therapy. 2020 Oct. 27;38(1):782-791.
Bai X, Hippensteel J, Leavitt A, Maloney JP, Beckham D, Garcia C, et al. Hypothesis: Alpha-1-antitrypsin is a promising treatment option for COVID-19. Medical Hypotheses. 2021 Jan.;146:110394.
Obermayer A, Jakob L-M, Haslbauer JD, Matter MS, Tzankov A, Stoiber W. Neutrophil Extracellular Traps in Fatal COVID-19-Associated Lung Injury. Pichler R, editor. Disease Markers [Internet]. 2021 Jul. 30 [cited 2021 Nov. 28];2021:1-10. Disponível em: https://pubmed.ncbi.nlm.nih.gov/34367376/
Pandolfi L, Bozzini S, Frangipane V, Percivalle E, De Luigi A, Violatto MB, et al. Neutrophil Extracellular Traps Induce the Epithelial-Mesenchymal Transition: Implications in Post-COVID-19 Fibrosis. Frontiers in Immunology. 2021 Jun. 14;12.
Latreille E, Lee WL. Interactions of Influenza and SARS-CoV-2 with the Lung Endothelium: Similarities, Differences, and Implications for Therapy. Viruses [Internet]. 2021 Jan 22 [cited 2021 Nov. 28];13(2):161. Disponível em: https://pubmed.ncbi.nlm.nih.gov/33499234/
González-Villalva A, De La Peña-Díaz A, Rojas-Lemus M, López-Valdez N, Ustarroz-Cano M, García-Peláez I, et al. Fisiología de la hemostasia y su alteración por la coagulopatía en COVID-19. Revista de la Facultad de Medicina [Internet]. 2020 [cited 2020 nov. 2];63. Disponível em: https://www.medigraphic.com/pdfs/facmed/un-2020/un205h.pdf
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