TABLE 1.
Objectives of the research program
| PATHOGENESIS (WP1&2) |
| HEMOSTASIS IN VIVO |
| Main objective: to unravel pathophysiological mechanisms that cause COVID‐19–associated coagulopathy. |
| 1. Investigate the presence of prothrombotic autoantibodies. |
| 2. Investigate the status of the fibrinolytic system. |
| 3. Evaluate the balance of the coagulation system. |
| 4. Analyze the composition of thrombi in tissues specimens. |
| 5. Identify molecular players and biomarkers for thrombosis. |
| VIROLOGY‐HEMOSTASIS IN VITRO |
| Main objective: to identify the molecular mechanisms of SARS‐CoV‐2–induced thrombosis using in vitro infection models of the pulmonary vascular bed. Tropism of SARS‐CoV‐2–infected endothelial cells will be compared to other respiratory viruses that cause VTE. |
| 1. Determine the role of respiratory epithelial cells in inducing a procoagulant state in pulmonary microvascular endothelial cells. |
| 2. Determine the role of activated monocytes from patients with COVID‐19 in inducing a procoagulant state in endothelial cells. |
| 3. Correlate data from in vitro experiments to pathology observations in autopsies. |
| 4. Determine the possible effect of nonneutralizing antibodies on SARS‐CoV‐2 infection kinetics and dynamics in respiratory endothelial cells, epithelial cells, and monocytes. |
| THROMBOPROPHYLAXIS AND TREATMENT OF THROMBOSIS (WP3) |
| Main objective: to define the optimal strategies for prevention and treatment of VTE in patients with COVID‐19. |
| 1. Investigate efficacy and safety of different doses of thromboprophylaxis. |
| 2. Investigate if therapeutic‐dose LMWH is superior to prophylaxis |
| 3. Investigate efficacy and safety of VTE treatment |
| BIOMARKERS AND PREDICTION OF THROMBOSIS (WP4) |
| Main objective: to predict the risk of VTE in admitted patients with COVID‐19 |
| 1. Develop and validate a dynamic prediction model to estimate individual VTE risks. |
| 2. Compare the predictive value between different mechanistic pathways, for different VTE phenotypes, and for the ward and ICU separately. |
| LONG‐TERM CONSEQUENCES OF VTE (WP5) |
| Main objective: to assess the impact and long‐term consequences of VTE in patients with COVID‐19. |
| 1. Evaluate the incidence of COVID‐19 associated VTE after hospital discharge. |
| 2. Assess patient‐reported outcome measures and pulmonary and cardiac function. |
| 3. Establish the rate of thrombus resolution and the incidence of post‐VTE syndromes. |
COVID‐19, coronavirus disease 2019; ICU, intensive care unit; LMWH, low‐molecular‐weight heparin; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; VTE, venous thromboembolism; WP, work package.