Evolution of NETosis markers and DAMPs have prognostic value in critically ill COVID-19 patients

Joram Huckriede, Sara Bulow Anderberg, Albert Morales, Femke de Vries, Michael Hultstrom, Anders Bergqvist, Jose T. Ortiz-Perez, Jan Willem Sels, Kanin Wichapong, Miklos Lipcsey, Marcel van de Poll, Anders Larsson, Tomas Luther, Chris Reutelingsperger, Pablo Garcia de Frutos, Robert Frithiof, Gerry A. F. Nicolaes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Web of Science)

Abstract

Coronavirus disease 19 (COVID-19) presents with disease severities of varying degree. In its most severe form, infection may lead to respiratory failure and multi-organ dysfunction. Here we study the levels and evolution of the damage associated molecular patterns (DAMPS) cell free DNA (cfDNA), extracellular histone H3 (H3) and neutrophil elastase (NE), and the immune modulators GAS6 and AXL in relation to clinical parameters, ICU scoring systems and mortality in patients (n=100) with severe COVID-19. cfDNA, H3, NE, GAS6 and AXL were increased in COVID-19 patients compared to controls. These measures associated with occurrence of clinical events and intensive care unit acquired weakness (ICUAW). cfDNA and GAS6 decreased in time in patients surviving to 30 days post ICU admission. A decrease of 27.2 ng/mL cfDNA during ICU stay associated with patient survival, whereas levels of GAS6 decreasing more than 4.0 ng/mL associated with survival. The presence of H3 in plasma was a common feature of COVID-19 patients, detected in 38% of the patients at ICU admission. NETosis markers cfDNA, H3 and NE correlated well with parameters of tissue damage and neutrophil counts. Furthermore, cfDNA correlated with lowest p/f ratio and a lowering in cfDNA was observed in patients with ventilator-free days.

Original languageEnglish
Article number15701
Number of pages12
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - 3 Aug 2021

Keywords

  • NEUTROPHIL EXTRACELLULAR TRAPS
  • ACUTE LUNG INJURY
  • PLASMA-LEVELS
  • HISTONES
  • GAS6
  • INFLAMMATION
  • ELASTASE

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