Evolving information has identified disease mechanisms and dysregulation of host biology that might be targeted therapeutically in COVID-19. Thrombosis and coagulopathy, associated with pulmonary injury and inflammation, are emerging clinical features of COVID-19. We present a framework for mechanisms of thrombosis in COVID-19 that initially derive from interaction of SARS-CoV-2 with ACE2, resulting in dysregulation of angiotensin signaling and subsequent inflammation and tissue injury. These responses result in increased signaling by thrombin (proteinase-activated) and purinergic receptors, which promote platelet activation and exert pathological effects on other cell types (e.g., endothelial cells, epithelial cells, fibroblasts), further enhancing inflammation and injury. Inhibitors of thrombin and purinergic receptors may thus have therapeutic effects by blunting platelet-mediated thromboinflammation and dysfunction in other cell types. Such inhibitors include agents (e.g., anti-platelet drugs) approved for other indications and that could be repurposed to treat, and potentially improve the outcome of, COVID-19 patients.

中文翻译：

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COVID-19 病理生理学中的炎症和血栓形成：蛋白酶激活和嘌呤能受体作为驱动因素和候选治疗靶点

不断发展的信息已经确定了可能在 COVID-19 中成为治疗目标的疾病机制和宿主生物学的失调。与肺损伤和炎症相关的血栓形成和凝血病是 COVID-19 的新临床特征。我们提出了 COVID-19 血栓形成机制的框架，该机制最初源自 SARS-CoV-2 与 ACE2 的相互作用，导致血管紧张素信号传导失调以及随后的炎症和组织损伤。这些反应导致凝血酶（蛋白酶激活的）和嘌呤能受体的信号传导增加，促进血小板活化并对其他细胞类型（例如内皮细胞、上皮细胞、成纤维细胞）发挥病理作用，进一步增强炎症和损伤。因此，凝血酶和嘌呤能受体的抑制剂可能通过减弱其他细胞类型中血小板介导的血栓炎症和功能障碍而具有治疗作用。此类抑制剂包括批准用于其他适应症的药物（例如抗血小板药物），这些药物可重新用于治疗 COVID-19 患者，并有可能改善其结果。