Evaluation and comparison of NETosis biomarkers in sepsis and COVID-19 patients

ABSTRACT

Background: Neutrophils are involved in the defense of the body against pathogens through the formation neutrophil extracellular trap, a mechanism called NETosis. These pathogens can be fungi, bacteria, viruses or other microorganisms. However, neutrophils through NETs have a double-edged sword activity and can also be harmful. Aim(s) This study aims to evaluate biomarkers of NETosis in two different patient populations admitted to the intensive care unit, i.e. COVID-19 and sepsis patients. A control population of matched subjects have been included. Method(s) Among the individuals admitted to the ICU and included in this study, 46 were sepsis patients and 22 were COVID-19 patients. 48 controls were included. Nucleosome histone H3.1, nucleosome citrullinated histone H3R8, free citrullinated histone (citrullinated at R2, R8 and R17), neutrophil elastase an myeloperoxidase were measured. Blood samples were taken at the admission to the intensive care unit. The different groups were compared using ordinary two-way ANOVA with a Tukey's multiple comparison on log-transformed data. Result(s) A significant difference in the levels of Nu.H3.1 and NE was observed between sepsis and COVID-19 subjects. All NETosis parameters differs in ICU patients versus controls. A positive correlation was found between SOFA and APCHE-II score and Nu.H3.1 in sepsis patients. No positive correlation was observed in COVID-19 patients. Normalization of NETosis parameters according to the neutrophil count improves the sensitivity of Nu.H3.1 to discriminate between sepsis and COVID-19 patients. The other parameters were also influenced but to a lesser extent. NE and Nu.H3.1 correlates well in sepsis patients while it is not the case in COVID-19 patients. Conclusion(s) Nu.H3.1 appears to be an interesting marker of NETosis in sepsis and COVID-19 patients. Its correlation with NE in sepsis patients reveals that NE is important in generating circulating nucleosomes while its weak association in COVID-19 suggest different patterns between the diseases.