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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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 languageEnglish
Article number1038
Issue number8
Publication statusPublished - Aug 2022


  • 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


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