Patients with COVID-19 in the dark-NETs of neutrophils

Maximilian Ackermann, Hans Joachim Anders, Rostyslav Bilyy, Gary L. Bowlin, Christoph Daniel, Rebecca De Lorenzo, Mikala Egeblad, Timo Henneck, Andrés Hidalgo, Markus Hoffmann, Bettina Hohberger, Yogendra Kanthi, Mariana J. Kaplan, Jason S. Knight, Jasmin Knopf, Elzbieta Kolaczkowska, Paul Kubes, Moritz Leppkes, Aparna Mahajan, Angelo A. ManfrediChristian Maueröder, Norma Maugeri, Ioannis Mitroulis, Luis E. Muñoz, Teluguakula Narasaraju, Elisabeth Naschberger, Indira Neeli, Lai Guan Ng, Marko Z. Radic, Konstantinos Ritis, Patrizia Rovere-Querini, Mirco Schapher, Christine Schauer, Hans Uwe Simon, Jeeshan Singh, Panagiotis Skendros, Konstantin Stark, Michael Stürzl, Johan van der Vlag, Peter Vandenabeele, Ljubomir Vitkov, Maren von Köckritz-Blickwede, Cansu Yanginlar, Shida Yousefi, Alexander Zarbock, Georg Schett, Martin Herrmann*

*Corresponding author for this work
143 Citations (Scopus)

Abstract

SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.

Original languageEnglish
JournalCell Death and Differentiation
Volume28
Issue number11
Pages (from-to)3125-3139
Number of pages15
ISSN1350-9047
DOIs
Publication statusPublished - 11.2021

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

  • 204-05 Immunology

Coronavirus related work

  • Research on SARS-CoV-2 / COVID-19

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