tetano
Editor, Senior Moderator
Res Pract Thromb Haemost
. 2020 Jun 12;4(4):506-509.
doi: 10.1002/rth2.12362. eCollection 2020 May.
COVID-19 Hypothesis: Activated Protein C for Therapy of Virus-Induced Pathologic Thromboinflammation
John H Griffin[SUP] 1 2 [/SUP], Patrick Lyden[SUP] 3 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID‐19; D‐dimer; SARS‐CoV‐2; activated protein C; coronavirus; cytokine.
. 2020 Jun 12;4(4):506-509.
doi: 10.1002/rth2.12362. eCollection 2020 May.
COVID-19 Hypothesis: Activated Protein C for Therapy of Virus-Induced Pathologic Thromboinflammation
John H Griffin[SUP] 1 2 [/SUP], Patrick Lyden[SUP] 3 [/SUP]
Affiliations
- PMID: 32548551
- PMCID: PMC7292662
- DOI: 10.1002/rth2.12362
Abstract
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.
Keywords: COVID‐19; D‐dimer; SARS‐CoV‐2; activated protein C; coronavirus; cytokine.