COVID-19 Sepsis: Based on Molecular Hemostatic Mechanism

Abstract

The pathogenetic mechanism of macrothrombosis typified by pulmonary thromboembolism (PTE) and deep vein throm- bosis (DVT) coexisting with ARDS in COVID-19 will be discussed from the concept of the hemostatic fundamentals. Acute respiratory distress syndrome (ARDS) is a hallmark of COVID-19 sepsis and results from the virus' pulmonary tropism and the host's endothelial heterogeneity. Patients with Multiorgan Dysfunction Syndrome (MODS) who have ARDS typically have disseminated vascular microthrombotic disease (VMTD). In response to the viral septicemia, the host activates the complement system which produces terminal complement complex C5b-9 to neutralize pathogen. C5b-9 causes pore formation on the membrane of host endothelial cells (ECs) if CD59 is underexpressed. Also, viral S protein attraction to endothelial ACE2 receptor damages ECs. However, EA-VMTD may orchestrate more complex clinical phenotypes, such as thrombotic thrombocytopenic purpura (TTP)-like syndrome, hepatic coagulopathy, MODS, and combined micro-macrothrombotic syndrome. In COVID-19, microthrombosis initially affects the lungs per tropism causing ARDS. ARDS and pulmonary thromboembolism (PTE) have frequently coexisted in this pandemic. Analysis based on two hemostatic theories suggests that PTE caused by activated ULVWF and TF paths is macrothrombosis and ARDS caused by activated ULVWF path is EA-VMTD. The thrombotic disorder of COVID-19 sepsis is consistent with the concept that ARDS is virus-induced disseminated EA- VMTD and PTE is in-hospital vascular injury-related macrothrombosis which is not directly related to viral pathogenesis. The pathogenesis-based therapeutic approach is discussed for the treatment of EA-VMTD with antimicrothrombotic regimen and the potential need of antic- oagulation therapy for coinciding macrothrombosis in comprehensive COVID-19 care.