Head-to-head comparison of cytokines storm-coagulopathy in septic shock and COVID-19

Abstract

IntroductionHost immune response to the coronavirus disease 2019 (COVID-19) 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 responses, their clinical outcomes are different.ObjectiveWe investigated and compared coagulopathy between septic shock and critical COVID-19 patients.MethodSeptic shock patients were diagnosed following the Survival Sepsis Campaign guidelines. COVID-19 patients were admitted in intensive care unit (ICU) for severe acute respiratory distress syndrome. Both were included in the study within 2 days after admission. Biomarkers were measured by ELISA from patient's plasma.ResultsWe 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 TLT-1 were specifically heightened in septic shock whereas CD40L was only augmented in COVID-19. Coagulation markers were increased in a disease-dependent way, with PAI-1, tPA and D-Dimers higher in septic shock and fibrinogen level, higher in COVID-19.DiscussionCOVID-19 patients had longer length-of-stay with more pronounced respiratory failure. This strong lung disruption overtime induced plasmatic TF 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.