Serum from COVID-19 patients promotes endothelial cells activation through protease-activated receptor 2

Endothelial dysfunction plays a central role in the pathophysiology of COVID-19 and is closely linked to the severity and mortality of the disease. The inflammatory response to infection can alter the capacity of the endothelium to regulate vascular tone, immune responses, and the balance between anti-thrombotic and pro-thrombotic properties. However, the specific endothelial pathways altered during COVID-19 are not yet fully understood. In this study, we sought to identify molecular changes in endothelial cells induced by circulating factors characteristic of COVID-19. To this aim, we cultured endothelial cells with serum from patients with COVID-19 or non-COVID-19 pneumonia. Through transcriptomic analysis, we were able to identify a distinctive endothelial phenotype that is induced by COVID-19 patient serum in the lack of endothelial infection This phenotype is characterized by increased apoptosis and the up-regulation of several immune response-related molecules, some of which are implicated in hypercoagulability. Our findings suggest that these effects are mediated, at least in part, by protease-activated receptor 2 (PAR-2), as predicted by transcriptome network analysis and validated in vitro using PAR-2 specific modulators.