NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study

Laure Morimont; Mélanie Dechamps; Clara David; Céline Bouvy; Constant Gillot; Hélène Haguet; Julien Favresse; Lorian Ronvaux; Julie Candiracci; Marielle Herzog; Pierre-François Laterre; Julien De Poortere; Sandrine Horman; Christophe Beauloye; Jonathan Douxfils

doi:10.3390/biom12081038

NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study

Laure Morimont, Mélanie Dechamps, Clara David, Céline Bouvy, Constant Gillot, Hélène Haguet, Julien Favresse, Lorian Ronvaux, Julie Candiracci, Marielle Herzog, Pierre-François Laterre, Julien De Poortere, Sandrine Horman, Christophe Beauloye, Jonathan Douxfils

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Abstract

Background: Neutrophil extracellular traps’ (NETs’) formation is a mechanism of defense that neutrophils deploy as an alternative to phagocytosis, to constrain the spread of microorganisms. Aim: The aim was to evaluate biomarkers of NETs’ formation in a patient cohort admitted to intensive care unit (ICU) due to infection. Methods: Forty-six septic shock patients, 22 critical COVID-19 patients and 48 matched control subjects were recruited. Intact nucleosomes containing histone 3.1 (Nu.H3.1), or citrullinated histone H3R8 (Nu.Cit-H3R8), free citrullinated histone (Cit-H3), neutrophil elastase (NE) and myeloperoxidase (MPO) were measured. Results: Significant differences in Nu.H3.1 and NE levels were observed between septic shock and critical COVID-19 subjects as well as with controls (p-values < 0.05). The normalization of nucleosome levels according to the neutrophil count improved the discrimination between septic shock and critical COVID-19 patients. The ratio of Nu.Cit-H3R8 to Nu.H3.1 allowed the determination of nucleosome citrullination degree, presumably by PAD4. Conclusions: H3.1 and Cit-H3R8 nucleosomes appear to be interesting markers of global cell death and neutrophil activation when combined. Nu.H3.1 permits the evaluation of disease severity and differs between septic shock and critical COVID-19 patients, reflecting two distinct potential pathological processes in these conditions.

Original language	English
Article number	1038
Journal	Biomolecules
Volume	12
Issue number	8
DOIs	https://doi.org/10.3390/biom12081038
Publication status	Published - Aug 2022

Keywords

Biomarkers/metabolism
COVID-19
Extracellular Traps/metabolism
Histones/metabolism
Humans
Neutrophils/metabolism
Nucleosomes/metabolism
Shock, Septic/metabolism
SARS-CoV-2
septic shock
nucleosomes
NETs’ formation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/biom12081038

11924-2022-MorimontFinal published version, 629 KB

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Morimont, L., Dechamps, M., David, C., Bouvy, C., Gillot, C., Haguet, H., Favresse, J., Ronvaux, L., Candiracci, J., Herzog, M., Laterre, P.-F., De Poortere, J., Horman, S., Beauloye, C., & Douxfils, J. (2022). NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study. Biomolecules, 12(8), Article 1038. https://doi.org/10.3390/biom12081038

@article{db6ae5ba3709460fb606f4489aff9cbb,

title = "NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study",

abstract = "Background: Neutrophil extracellular traps{\textquoteright} (NETs{\textquoteright}) formation is a mechanism of defense that neutrophils deploy as an alternative to phagocytosis, to constrain the spread of microorganisms. Aim: The aim was to evaluate biomarkers of NETs{\textquoteright} formation in a patient cohort admitted to intensive care unit (ICU) due to infection. Methods: Forty-six septic shock patients, 22 critical COVID-19 patients and 48 matched control subjects were recruited. Intact nucleosomes containing histone 3.1 (Nu.H3.1), or citrullinated histone H3R8 (Nu.Cit-H3R8), free citrullinated histone (Cit-H3), neutrophil elastase (NE) and myeloperoxidase (MPO) were measured. Results: Significant differences in Nu.H3.1 and NE levels were observed between septic shock and critical COVID-19 subjects as well as with controls (p-values < 0.05). The normalization of nucleosome levels according to the neutrophil count improved the discrimination between septic shock and critical COVID-19 patients. The ratio of Nu.Cit-H3R8 to Nu.H3.1 allowed the determination of nucleosome citrullination degree, presumably by PAD4. Conclusions: H3.1 and Cit-H3R8 nucleosomes appear to be interesting markers of global cell death and neutrophil activation when combined. Nu.H3.1 permits the evaluation of disease severity and differs between septic shock and critical COVID-19 patients, reflecting two distinct potential pathological processes in these conditions.",

keywords = "Biomarkers/metabolism, COVID-19, Extracellular Traps/metabolism, Histones/metabolism, Humans, Neutrophils/metabolism, Nucleosomes/metabolism, Shock, Septic/metabolism, SARS-CoV-2, septic shock, nucleosomes, NETs{\textquoteright} formation",

author = "Laure Morimont and M{\'e}lanie Dechamps and Clara David and C{\'e}line Bouvy and Constant Gillot and H{\'e}l{\`e}ne Haguet and Julien Favresse and Lorian Ronvaux and Julie Candiracci and Marielle Herzog and Pierre-Fran{\c c}ois Laterre and {De Poortere}, Julien and Sandrine Horman and Christophe Beauloye and Jonathan Douxfils",

note = "Funding Information: This work was supported by grants from the Fondation Saint-Luc (Brussels, Belgium). The Division of Cardiology at Cliniques Universitaires St Luc, Belgium, has received unrestricted research grants from AstraZeneca (Belgium). M.D. is Clinical Master Specialist Applicant to a Ph.D. at the Fonds National de la Recherche Scientifique et M{\'e}dicale (FNRS, Belgium). J.D.P. was supported by a grant from the Salus Sanguinis Foundation (UCLouvain, Belgium). S.H. is senior research associates at FNRS. QUALIblood s.a. (Belgium) offered the analyses for determining the cytokinic profile and Belgian Volition SRL (Belgium) offered the Nu.Q kits. Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = aug,

doi = "10.3390/biom12081038",

language = "English",

volume = "12",

journal = "Biomolecules",

issn = "2218-273X",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "8",

}

Morimont, L, Dechamps, M, David, C , Bouvy, C , Gillot, C , Haguet, H , Favresse, J , Ronvaux, L, Candiracci, J, Herzog, M, Laterre, P-F, De Poortere, J, Horman, S, Beauloye, C & Douxfils, J 2022, 'NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study', Biomolecules, vol. 12, no. 8, 1038. https://doi.org/10.3390/biom12081038

TY - JOUR

T1 - NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients

T2 - An Observational Study

AU - Morimont, Laure

AU - Dechamps, Mélanie

AU - David, Clara

AU - Bouvy, Céline

AU - Gillot, Constant

AU - Haguet, Hélène

AU - Favresse, Julien

AU - Ronvaux, Lorian

AU - Candiracci, Julie

AU - Herzog, Marielle

AU - Laterre, Pierre-François

AU - De Poortere, Julien

AU - Horman, Sandrine

AU - Beauloye, Christophe

AU - Douxfils, Jonathan

N1 - Funding Information: This work was supported by grants from the Fondation Saint-Luc (Brussels, Belgium). The Division of Cardiology at Cliniques Universitaires St Luc, Belgium, has received unrestricted research grants from AstraZeneca (Belgium). M.D. is Clinical Master Specialist Applicant to a Ph.D. at the Fonds National de la Recherche Scientifique et Médicale (FNRS, Belgium). J.D.P. was supported by a grant from the Salus Sanguinis Foundation (UCLouvain, Belgium). S.H. is senior research associates at FNRS. QUALIblood s.a. (Belgium) offered the analyses for determining the cytokinic profile and Belgian Volition SRL (Belgium) offered the Nu.Q kits. Publisher Copyright: © 2022 by the authors.

PY - 2022/8

Y1 - 2022/8

N2 - Background: Neutrophil extracellular traps’ (NETs’) formation is a mechanism of defense that neutrophils deploy as an alternative to phagocytosis, to constrain the spread of microorganisms. Aim: The aim was to evaluate biomarkers of NETs’ formation in a patient cohort admitted to intensive care unit (ICU) due to infection. Methods: Forty-six septic shock patients, 22 critical COVID-19 patients and 48 matched control subjects were recruited. Intact nucleosomes containing histone 3.1 (Nu.H3.1), or citrullinated histone H3R8 (Nu.Cit-H3R8), free citrullinated histone (Cit-H3), neutrophil elastase (NE) and myeloperoxidase (MPO) were measured. Results: Significant differences in Nu.H3.1 and NE levels were observed between septic shock and critical COVID-19 subjects as well as with controls (p-values < 0.05). The normalization of nucleosome levels according to the neutrophil count improved the discrimination between septic shock and critical COVID-19 patients. The ratio of Nu.Cit-H3R8 to Nu.H3.1 allowed the determination of nucleosome citrullination degree, presumably by PAD4. Conclusions: H3.1 and Cit-H3R8 nucleosomes appear to be interesting markers of global cell death and neutrophil activation when combined. Nu.H3.1 permits the evaluation of disease severity and differs between septic shock and critical COVID-19 patients, reflecting two distinct potential pathological processes in these conditions.

AB - Background: Neutrophil extracellular traps’ (NETs’) formation is a mechanism of defense that neutrophils deploy as an alternative to phagocytosis, to constrain the spread of microorganisms. Aim: The aim was to evaluate biomarkers of NETs’ formation in a patient cohort admitted to intensive care unit (ICU) due to infection. Methods: Forty-six septic shock patients, 22 critical COVID-19 patients and 48 matched control subjects were recruited. Intact nucleosomes containing histone 3.1 (Nu.H3.1), or citrullinated histone H3R8 (Nu.Cit-H3R8), free citrullinated histone (Cit-H3), neutrophil elastase (NE) and myeloperoxidase (MPO) were measured. Results: Significant differences in Nu.H3.1 and NE levels were observed between septic shock and critical COVID-19 subjects as well as with controls (p-values < 0.05). The normalization of nucleosome levels according to the neutrophil count improved the discrimination between septic shock and critical COVID-19 patients. The ratio of Nu.Cit-H3R8 to Nu.H3.1 allowed the determination of nucleosome citrullination degree, presumably by PAD4. Conclusions: H3.1 and Cit-H3R8 nucleosomes appear to be interesting markers of global cell death and neutrophil activation when combined. Nu.H3.1 permits the evaluation of disease severity and differs between septic shock and critical COVID-19 patients, reflecting two distinct potential pathological processes in these conditions.

KW - Biomarkers/metabolism

KW - COVID-19

KW - Extracellular Traps/metabolism

KW - Histones/metabolism

KW - Humans

KW - Neutrophils/metabolism

KW - Nucleosomes/metabolism

KW - Shock, Septic/metabolism

KW - SARS-CoV-2

KW - septic shock

KW - nucleosomes

KW - NETs’ formation

UR - http://www.scopus.com/inward/record.url?scp=85137126224&partnerID=8YFLogxK

U2 - 10.3390/biom12081038

DO - 10.3390/biom12081038

M3 - Article

C2 - 36008932

SN - 2218-273X

VL - 12

JO - Biomolecules

JF - Biomolecules

IS - 8

M1 - 1038

ER -

NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study

Abstract

Keywords

UN SDGs

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Clinical Pharmacology Research Group

The COVILAB project : Clinical laboratory investigations related to COVID-19