Seriously ill patients with coronavirus disease 2019 (COVID‐19) at risk for death exhibit elevated cytokine and chemokine levels and D‐dimer, and they often have comorbidities related to vascular dysfunctions. In preclinical studies, activated protein C (APC) provides negative feedback downregulation of excessive inflammation and thrombin generation, attenuates damage caused by ischemia‐reperfusion in many organs including lungs, and reduces death caused by bacterial pneumonia. APC exerts both anticoagulant activities and direct cell‐signaling activities. Preclinical studies show that its direct cell‐signaling actions mediate anti‐inflammatory and anti‐apoptotic actions, mortality reduction for pneumonia, and beneficial actions for ischemia‐reperfusion injury. The APC mutant 3K3A‐APC, which was engineered to have diminished anticoagulant activity while retaining cell‐signaling actions, was safe in phase 1 and phase 2 human trials. Because of its broad spectrum of homeostatic effects in preclinical studies, we speculate that 3K3A‐APC merits consideration for clinical trial studies in appropriately chosen, seriously ill patients with COVID‐19.
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机译：严重生病的患者2019年（Covid-19）的死亡风险表现出升高的细胞因子和趋化因子水平和D-二聚体，并且它们通常具有与血管功能障碍有关的合并症。在临床前研究中，活化蛋白C（APC）提供过量的炎症和凝血酶产生的负反馈，并衰减在包括肺部的许多器官中缺血再灌注造成的损伤，并减少了细菌肺炎引起的死亡。 APC施加抗凝血活动和直接的细胞信号传导活动。临床前研究表明，其直接细胞信号动作介导抗炎和抗凋亡作用，降低肺炎的死亡率，以及缺血再灌注损伤的有益作用。 APC突变体3K3A-APC在抗凝血活性的同时在保持细胞信号动作的同时减少，在第1阶段和第2期人类试验中是安全的。 Because of its broad spectrum of homeostatic effects in preclinical studies, we speculate that 3K3A‐APC merits consideration for clinical trial studies in appropriately chosen, seriously ill patients with COVID‐19.
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