Tissue factor links inflammation, thrombosis, and senescence in COVID-19

COVID-19 is a highly contagious respiratory infection that induces inflammatory and thrombotic responses. Upon SARS-CoV-2 entry into lung epithelial cells, infected cells secrete a group of chemokines known as the senescence associated secretory phenotype (SASP). These SASP factors induce the harmful COVID-19 cytokine storm by recruiting and activating inflammatory immune cells. Recent studies propose viral-induced senescence (VIS) is responsible for releasing these SASP factors and exacerbating inflammation in COVID-19. However, it is still unclear how thrombosis, inflammation, and senescence are connected, and whether senescence is commonly triggered after infection. Additionally the underlying mechanism of thrombosis in COVID-19 remains unknown. Here, we conducted meta-analysis of single-cell and bulk RNA sequencing data from multiple patient studies, animal models, and cell lines infected with SARS-CoV-2 and other respiratory viruses. We found that SASP factors are prevalent in infected patients and that tissue factor (F3), initiator of the extrinsic coagulation pathway, was positively correlated with SASP expression. Notably, F3 is overexpressed in various respiratory viral infections including COVID-19 and is positively correlated with thrombosis and inflammatory SASP factor production. Together, these data indicate F3 links inflammation, thrombosis, and senescence during infection, and propose F3 as a target protein for antiviral treatment.