Understanding COVID-19-associated coagulopathy

Abstract

COVID-19-associated coagulopathy (CAC) is a life-threatening complication of SARS-CoV-2 infection. However, the underlying cellular and molecular mechanisms driving this condition are unclear. Evidence supports the concept that CAC involves complex interactions between the innate immune response, the coagulation and fibrinolytic pathways, and the vascular endothelium, resulting in a procoagulant condition. Understanding of the pathogenesis of this condition at the genomic, molecular and cellular levels is needed in order to mitigate thrombosis formation in at-risk patients. In this Perspective, we categorize our current understanding of CAC into three main pathological mechanisms: first, vascular endothelial cell dysfunction; second, a hyper-inflammatory immune response; and last, hypercoagulability. Furthermore, we pose key questions and identify research gaps that need to be addressed to better understand CAC, facilitate improved diagnostics and aid in therapeutic development. Finally, we consider the suitability of different animal models to study CAC.

Fig. 1. Potential clinical consequences of COVID-19-associated coagulopathy.

COVID-19-associated coagulopathy (CAC) is characterized by coagulation disorders that affect multiple tissue and organ sites, and vary from skin purpura (also known as ‘COVID toe’) to myocardial infarction and neurological dysfunction. Circulating microthrombi and/or macrothrombi can lead to multi-organ injury or failure.

Fig. 2. Pathway contributing to COVID-19-associated coagulopathy.

COVID-19-associated coagulopathy (CAC) likely involves the dysregulation of numerous pathways that, in ways that are not currently well understood, culminate in endothelial damage, thrombosis and multi-organ failure. ACE2, angiotensin-converting enzyme 2; autoantibodies, anti-phospholipid-targeting autoantibodies; IFITM3, interferon-induced transmembrane protein 3; NET, neutrophil extracellular trap; PAI-1, plasminogen activator inhibitor 1; ROS, reactive oxygen species; vWF, von Willebrand factor. Adapted with permission from ref., Elsevier.