Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques.
Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques.
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DOI：
10.1016/j.cell.2020.10.005
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发表时间：
2020-11-25
期刊：
影响因子：
64.5
通讯作者：
Barouch DH
中科院分区：
文献类型：
--
作者：
Aid M;Busman-Sahay K;Vidal SJ;Maliga Z;Bondoc S;Starke C;Terry M;Jacobson CA;Wrijil L;Ducat S;Brook OR;Miller AD;Porto M;Pellegrini KL;Pino M;Hoang TN;Chandrashekar A;Patel S;Stephenson K;Bosinger SE;Andersen H;Lewis MG;Hecht JL;Sorger PK;Martinot AJ;Estes JD;Barouch DH
COVID-19疫情导致全球范围内的发病率及死亡率大幅上升。驱动人类SARS-CoV-2发病机制的临床特征包括炎症和血栓形成，但这些过程的机制细节仍有待确定。在这项研究中，我们证明了内皮细胞破坏和血管血栓形成的肺组织病理切片从人类和恒河猴感染SARS-CoV-2。为了确定与SARS-CoV-2在猕猴中发病机制相关的关键分子途径，我们对支气管肺泡灌洗液和外周血进行了转录组学分析，并对血清进行了蛋白质组学分析。我们观察到肺中巨噬细胞浸润以及巨噬细胞、补体、血小板活化、血栓形成和促炎标志物（包括C-反应蛋白、MX 1、IL-6、IL-1、IL-8、TNFα和NF-κB）的上调。这些结果表明，炎症和血栓形成途径之间的关键相互作用导致SARS-CoV-2诱导的血管疾病的模型。我们的研究结果为COVID-19提供了潜在的治疗靶点。Aid等人显示SARS-CoV-2通过诱导促炎细胞因子的上调，在人类和恒河猴肺中引起内皮破坏和血管血栓形成。使用一种结合猕猴组织病理学和多组学的方法，他们显示了随着时间的推移血管疾病的进展，其中涉及补体，巨噬细胞，细胞因子和血栓级联反应。
The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum. We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB. These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease. Our findings suggest potential therapeutic targets for COVID-19. Aid et al. show that SARS-CoV-2 causes endothelial disruption and vascular thrombosis in both human and rhesus macaques lungs by inducing an upregulation of proinflammatory cytokines. Using an approach that combines histopathology and multiomics in macaques, they show the progression to vascular disease over time, which involves complement, macrophage, cytokine, and thrombosis cascades.
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