Abstract
Acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection continues to be a worldwide public health crisis. Among the several severe manifestations of this disease, thrombotic processes drive the catastrophic organ failure and mortality in these patients. In addition to a well-established cytokine storm associated with the disease, perturbations in platelets, endothelial cells, and the coagulation system are key in triggering systemic coagulopathy, involving both the macro- and microvasculatures of different organs. Of the several mechanisms that might contribute to dysregulation of these cells following SARS-CoV-2 infection, the current review focuses on the role of activated Janus kinase (JAK) signaling in augmenting thrombotic processes and organ dysfunction. The review concludes with presenting the current understanding and emerging controversies concerning the potential therapeutic applications of JAK inhibitors for ameliorating the inflammation-thrombosis phenotype in COVID-19 patients.
Highlights
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Coronavirus Disease-19 (COVID-19) is a worldwide public health crisis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Emerging literature has uncovered another aspect of Janus kinase (JAK)–signal transducer and activators of transcription (STAT) regulation in patients with COVID-19 that is provocative in nature
Summary
Among several potential surface receptors for entry of SARS-CoV-2 in target cells, such as CD209L/CD209 [29], the neuropilin receptor [30,31], and CD147/Basigin [32], the angiotensin-converting enzyme II (ACE2) is one well studied. ACE2 is responsible for the receptor-mediated endocytosis of SARS-CoV-2 into cells. The cell surface abundance of the ACE2 receptor is controlled by clathrin-dependent endocytosis [34]. The viral spike protein S1 subunit facilitates binding to the ACE2 receptor, while the spike protein S2 subunit is cleaved by type II transmembrane serine protease (TMPRSS2), which allows viral entry into the cell. This event is followed by replication, cellular metabolic damage and release of inflammatory cytokines [37]. Relevant to the current review, this effect is dependent on the Janus kinase (JAK) signaling cascade [39]
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