黑料网

Infections with influenza A virus (IAV) or SARS-CoV-2 are associated with increased thrombotic complications. Together with 黑料网 collaborators we showed that IAV infection leads to increased TF expression in lung epithelial cells (EpC). The increased TF expression was associated with increased coagulation activation (thrombin generation) in the lung. We propose that during viral induced acute lung injuries (ALI) like severe flu infections and COVID19, the host is exposed to viral genomic intermediates (dsRNA) and to the host’s own dsRNA. This triggers dsRNA-dependent immune responses leading to TF expression in lung EpCs. Importantly, monocytes do not express more TF when exposed to dsRNA. During viral ALI, the lung EpC TF comes in contact with blood component and is, also, released on extracellular vesicles (EVTF+). Together, it increases the local and systemic thrombotic potential of the blood. In support of this, we found that poly IC (dsRNA) stimulation can lead to increased TF expression in lung EpCs in vitro. We refined a non-infectious COVID19 model and we are now able to induce lung EpC TF in mice. We found that this was associated with increased coagulation activation and lung fibrin depositions indicating pulmonary micro-thrombosis. We found further, that the increased lung TF expression resulted in increased venous (macro-)thrombosis. Currently, we investigate new ways to reduce this TF-dependent increase in viral ALI-induced thrombosis.