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

COVID-19 is a highly contagious respiratory infection caused by the SARS-CoV-2 virus. The infected lung epithelial cells secrete a group of chemokines and cytokines, which triggers harmful cytokine storms and hyper-thrombotic responses. Recent studies have proposed that viral-induced senescence is responsible for cytokine release and inflammation in COVID-19 patients. However, it is unknown whether cellular senescence is commonly triggered after viral infection and how inflammation and thrombosis, hyper-activated in these patients, are functionally connected. To address these questions, we conducted a bioinformatics-based meta-analysis using single-cell and bulk RNA sequencing datasets obtained from human patient studies, animal models, and cell lines infected with SARS-CoV-2 and other respiratory viruses. We found that the senescence phenotype is robustly upregulated in most SARS-CoV-2-infected patients, especially in the infected lung epithelial cells. Notably, the upregulation of Tissue factor (F3), a key initiator of the extrinsic blood coagulation pathway, occurs concurrently with the upregulation of the senescence-associated secretory phenotype (SASP) factors. Furthermore, F3 levels are positively correlated with the senescence and hyper-coagulation gene signatures in COVID-19 patients. Together, these data demonstrate the prevalence of senescence in respiratory viral infection and suggest F3 as a critical link between inflammation, thrombosis, and senescence in these disease states.

Clotting disorder in severe acute respiratory syndrome coronavirus 2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human respiratory viral infection that has rapidly progressed into a pandemic, causing significant morbidity and mortality. Blood clotting disorders and acute respiratory failure have surfaced as the major complications among the severe cases of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection. Remarkably, more than 70% of deaths related to COVID-19 are attributed to clotting-associated complications such as pulmonary embolism, strokes and multi-organ failure. These vascular complications have been confirmed by autopsy. This study summarizes the current understanding and explains the possible mechanisms of the blood clotting disorder, emphasizing the role of (1) hypoxia-related activation of coagulation factors like tissue factor, a significant player in triggering coagulation cascade, (2) cytokine storm and activation of neutrophils and the release of neutrophil extracellular traps and (3) immobility and ICU related risk factors.