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Histone H3 Cleavage in Severe COVID-19 ICU Patients

The severity of coronavirus disease 19 (COVID-19) is associated with neutrophil extracellular trap (NET) formation. During NET formation, cytotoxic extracellular histones are released, the presence of which is linked to the initiation and progression of several acute inflammatory diseases. Here we s...

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Autores principales: Huckriede, Joram, de Vries, Femke, Hultström, Michael, Wichapong, Kanin, Reutelingsperger, Chris, Lipcsey, Miklos, Garcia de Frutos, Pablo, Frithiof, Robert, Nicolaes, Gerry A. F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461091/
https://www.ncbi.nlm.nih.gov/pubmed/34568088
http://dx.doi.org/10.3389/fcimb.2021.694186
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author Huckriede, Joram
de Vries, Femke
Hultström, Michael
Wichapong, Kanin
Reutelingsperger, Chris
Lipcsey, Miklos
Garcia de Frutos, Pablo
Frithiof, Robert
Nicolaes, Gerry A. F.
author_facet Huckriede, Joram
de Vries, Femke
Hultström, Michael
Wichapong, Kanin
Reutelingsperger, Chris
Lipcsey, Miklos
Garcia de Frutos, Pablo
Frithiof, Robert
Nicolaes, Gerry A. F.
author_sort Huckriede, Joram
collection PubMed
description The severity of coronavirus disease 19 (COVID-19) is associated with neutrophil extracellular trap (NET) formation. During NET formation, cytotoxic extracellular histones are released, the presence of which is linked to the initiation and progression of several acute inflammatory diseases. Here we study the presence and evolution of extracellular histone H3 and several other neutrophil-related molecules and damage-associated molecular patterns (DAMPs) in the plasma of 117 COVID-19-positive ICU patients. We demonstrate that at ICU admission the levels of histone H3, MPO, and DNA-MPO complex were all significantly increased in COVID-19-positive patients compared to control samples. Furthermore, in a subset of 54 patients, the levels of each marker remained increased after 4+ days compared to admission. Histone H3 was found in 28% of the patients on admission to the ICU and in 50% of the patients during their stay at the ICU. Notably, in 47% of histone-positive patients, we observed proteolysis of histone in their plasma. The overall presence of histone H3 during ICU stay was associated with thromboembolic events and secondary infection, and non-cleaved histone H3 was associated with the need for vasoactive treatment, invasive ventilation, and the development of acute kidney injury. Our data support the validity of treatments that aim to reduce NET formation and additionally underscore that more targeted therapies focused on the neutralization of histones should be considered as treatment options for severe COVID-19 patients.
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spelling pubmed-84610912021-09-25 Histone H3 Cleavage in Severe COVID-19 ICU Patients Huckriede, Joram de Vries, Femke Hultström, Michael Wichapong, Kanin Reutelingsperger, Chris Lipcsey, Miklos Garcia de Frutos, Pablo Frithiof, Robert Nicolaes, Gerry A. F. Front Cell Infect Microbiol Cellular and Infection Microbiology The severity of coronavirus disease 19 (COVID-19) is associated with neutrophil extracellular trap (NET) formation. During NET formation, cytotoxic extracellular histones are released, the presence of which is linked to the initiation and progression of several acute inflammatory diseases. Here we study the presence and evolution of extracellular histone H3 and several other neutrophil-related molecules and damage-associated molecular patterns (DAMPs) in the plasma of 117 COVID-19-positive ICU patients. We demonstrate that at ICU admission the levels of histone H3, MPO, and DNA-MPO complex were all significantly increased in COVID-19-positive patients compared to control samples. Furthermore, in a subset of 54 patients, the levels of each marker remained increased after 4+ days compared to admission. Histone H3 was found in 28% of the patients on admission to the ICU and in 50% of the patients during their stay at the ICU. Notably, in 47% of histone-positive patients, we observed proteolysis of histone in their plasma. The overall presence of histone H3 during ICU stay was associated with thromboembolic events and secondary infection, and non-cleaved histone H3 was associated with the need for vasoactive treatment, invasive ventilation, and the development of acute kidney injury. Our data support the validity of treatments that aim to reduce NET formation and additionally underscore that more targeted therapies focused on the neutralization of histones should be considered as treatment options for severe COVID-19 patients. Frontiers Media S.A. 2021-09-10 /pmc/articles/PMC8461091/ /pubmed/34568088 http://dx.doi.org/10.3389/fcimb.2021.694186 Text en Copyright © 2021 Huckriede, de Vries, Hultström, Wichapong, Reutelingsperger, Lipcsey, Garcia de Frutos, Frithiof and Nicolaes https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Huckriede, Joram
de Vries, Femke
Hultström, Michael
Wichapong, Kanin
Reutelingsperger, Chris
Lipcsey, Miklos
Garcia de Frutos, Pablo
Frithiof, Robert
Nicolaes, Gerry A. F.
Histone H3 Cleavage in Severe COVID-19 ICU Patients
title Histone H3 Cleavage in Severe COVID-19 ICU Patients
title_full Histone H3 Cleavage in Severe COVID-19 ICU Patients
title_fullStr Histone H3 Cleavage in Severe COVID-19 ICU Patients
title_full_unstemmed Histone H3 Cleavage in Severe COVID-19 ICU Patients
title_short Histone H3 Cleavage in Severe COVID-19 ICU Patients
title_sort histone h3 cleavage in severe covid-19 icu patients
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461091/
https://www.ncbi.nlm.nih.gov/pubmed/34568088
http://dx.doi.org/10.3389/fcimb.2021.694186
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