Computational modeling of hypercoagulability in COVID-19

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 100 million people worldwide and claimed millions of lives. While the leading cause of mortality in COVID-19 patients is the hypoxic respiratory failure from acute respiratory distress syndrome, emerging evidence suggested that people with COVID-19 are prone to experience thrombotic events, such as venous thrombosis, pulmonary embolism and arterial thrombosis, and develop cardiovascular complications. These findings raise attention about appropriate disease management to prevent or treat thrombosis for COVID-19 patients. Clinical data indicated that all the three factors of Virchow's triad, namely stasis, endothelial injury and hypercoagulable state, are likely to contribute to the increased risk for thrombosis in COVID-19. Here, we propose to develop a novel computational framework to simulate the undesired thrombosis in microcirculation, a prominent clinical feature of COVID-19. This new framework will integrate seamlessly the four key components in the process of clotting in hemostasis, including hemodynamics, transport of coagulation factors and coagulation kinetics, blood cell mechanics and platelet adhesive dynamics, such that we can dissect the complicated process of pathological thrombus formation in COVID-19 and investigate its underlying mechanism. Our simulation results can help to improve our understanding of the pathogenesis of hypercoagulability, identify the key factor that triggers thrombus formation and provide insights to explore new therapeutic approaches for the prevention and treatment of COVID-19-associated thrombosis.