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.
ABSTRACT
Background: Septic shock generates an important inflammatory reaction, endothelial activation and a procoagulant state leading to microvascular thrombosis and subsequent organ impairment [1]. Similarly, a severe inflammatory reaction and a coagulopathy with pulmonary micro-thrombosis eventually leading to acute lung injury, is a typical feature of critical form of Coronavirus disease 2019 (Covid-19) [2]. Our aim was to compare coagulation, platelet activation and plateletsneutrophils interplay between control, septic shock and critical Covid-19 patients. Methods/Materials: A total of 118 patients were included in our prospective, monocentric, observational study between February 2019 and June 2020. Septic shock (n=48) and Covid-19 (n=22) patients were consecutively included at admission in our ICU department. Control patients (n=48) with matched gender and co-morbidities were recruited at central lab consultation. Results: Septic shock patients had worse severity scores due to multiple organ failure (assessed by APACHE II and SOFA score) whereas Covid-19 patients had more severe respiratory failure and a longer ICU length-ofstay (Table 1). At the time of inclusion, CRP and lymphocyte count were comparable between septic shock and Covid-19 patients. White cell count ad neutrophil count was higher for septic shock patients. Analysis of coagulation showed a prolonged INR, TT and aPTT in septic shock although only INR was prolonged in Covid-19. Thrombin antithrombin complex (TATc) formation was similar in both pathologies, whereas consumption of antithrombin III (ATIII) and D-dimers formation was more pronounced in septic shock. Platelet count was lower in septic shock and platelet activation, assessed via plasmatic levels of soluble P-selectin (sCD62P) and Trem-like transcript 1 (sTLT-1), was more important in septic shock. Neutrophil activation and NETosis, evaluated by levels of circulating myeloperoxidase (MPO) and citrullinated histone 3 (H3-Cit), was similarly increased in both groups (Figure 1). Conclusions: This study confirmed an activation of coagulation cascade, platelet activation and NETosis in both septic shock and critical Covid-19, compared with control patients. Importantly, the extent of these changes was similar or less pronounced in critical COVID-19 compared with septic shock.
ABSTRACT
Background : Since December 2019, the coronavirus disease 2019 (Covid-19) is the main health concern around the world. Host immune response to the virus is variable and can induce a dysregulated inflammatory response associated with venous and arterial thrombosis called Covid-19 associated coagulopathy (CAC). During septic shock, inflammatory reaction generates endothelial activation and procoagulant state with microvascular thrombi inducing disseminated intravascular coagulation (DIC). Although CAC and DIC induce altered coagulation and fibrinolytic responses, their clinical outcomes are different. Aims : We investigated and compared coagulopathy between septic shock and critical Covid-19 patients. Methods : Septic shock patients were diagnosed following the Survival Sepsis Campaign guidelines. They were admitted in intensive care unit (ICU) and included in the study within 2 days after admission. Covid-19 patients were admitted in ICU for severe Acute Respiratory Distress Syndrome (ARDS) due to SARS-Cov2 infection and included within 2 days after admission. Patient's plasma was isolated and used to measure circulating biomarkers by ELISA. Results : We observed an increase in vWF and TFPI in both septic and Covid-19 patients compared to controls, highlighting endothelial damage. Interestingly, circulating TF was only elevated in Covid-19 patients. Platelet activation differed between the two cohorts of patients. P-selectin and Trem-like transcript 1 were specifically heightened in septic shock whereas CD40L was only augmented in Covid-19. Coagulation markers were increased in a diseasedependent way, with PAI-1, tPA and D-Dimers higher in septic shock and fibrinogen level, higher in Covid-19. Conclusions : Covid-19 patients had longer length-of-stay with more pronounced respiratory failure. This strong lung disruption overtime induced plasmatic tissue factor release with sustained inflammatory response characterized by sCD40L and fibrinogen secretion. Given the similarities between Covid-19 and septic shock regarding fibrinolysis and coagulation, but not platelet activation, endothelium seems to play a central role in Covid-19 and might explain the differences between CAC and DIC.