NETosis: A key player in autoimmunity, COVID-19, and long COVID

NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutro...

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Main Authors: Diana M. Monsalve, Yeny Acosta-Ampudia, Nicolás Guerrero Acosta, Mariana Celis-Andrade, Ali Şahin, Ahsen Morva Yilmaz, Yehuda Shoenfeld, Carolina Ramírez-Santana
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Journal of Translational Autoimmunity
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589909025000152
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author Diana M. Monsalve
Yeny Acosta-Ampudia
Nicolás Guerrero Acosta
Mariana Celis-Andrade
Ali Şahin
Ahsen Morva Yilmaz
Yehuda Shoenfeld
Carolina Ramírez-Santana
author_facet Diana M. Monsalve
Yeny Acosta-Ampudia
Nicolás Guerrero Acosta
Mariana Celis-Andrade
Ali Şahin
Ahsen Morva Yilmaz
Yehuda Shoenfeld
Carolina Ramírez-Santana
author_sort Diana M. Monsalve
collection DOAJ
description NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.
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publisher Elsevier
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series Journal of Translational Autoimmunity
spelling doaj-art-45281f737ef1425ab9f46cd0cb6d0d272025-08-20T02:05:36ZengElsevierJournal of Translational Autoimmunity2589-90902025-06-011010028010.1016/j.jtauto.2025.100280NETosis: A key player in autoimmunity, COVID-19, and long COVIDDiana M. Monsalve0Yeny Acosta-Ampudia1Nicolás Guerrero Acosta2Mariana Celis-Andrade3Ali Şahin4Ahsen Morva Yilmaz5Yehuda Shoenfeld6Carolina Ramírez-Santana7Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, ColombiaCenter for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, ColombiaCenter for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, ColombiaCenter for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, ColombiaSelcuk University, Faculty of Medicine, Konya, TurkiyeTUBITAK Marmara Research Center (TUBITAK-MAM), Life Sciences, Medical Biotechnology Unit, Kocaeli, TurkiyeZabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Reichman University, Herzelia, IsraelCenter for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia; Corresponding author. Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 No. 63-C-69, Bogotá, 111221, Colombia.NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.http://www.sciencedirect.com/science/article/pii/S2589909025000152NETsNeutrophilsSARS-CoV-2COVID-19AutoimmunityLong COVID
spellingShingle Diana M. Monsalve
Yeny Acosta-Ampudia
Nicolás Guerrero Acosta
Mariana Celis-Andrade
Ali Şahin
Ahsen Morva Yilmaz
Yehuda Shoenfeld
Carolina Ramírez-Santana
NETosis: A key player in autoimmunity, COVID-19, and long COVID
Journal of Translational Autoimmunity
NETs
Neutrophils
SARS-CoV-2
COVID-19
Autoimmunity
Long COVID
title NETosis: A key player in autoimmunity, COVID-19, and long COVID
title_full NETosis: A key player in autoimmunity, COVID-19, and long COVID
title_fullStr NETosis: A key player in autoimmunity, COVID-19, and long COVID
title_full_unstemmed NETosis: A key player in autoimmunity, COVID-19, and long COVID
title_short NETosis: A key player in autoimmunity, COVID-19, and long COVID
title_sort netosis a key player in autoimmunity covid 19 and long covid
topic NETs
Neutrophils
SARS-CoV-2
COVID-19
Autoimmunity
Long COVID
url http://www.sciencedirect.com/science/article/pii/S2589909025000152
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