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Vascular underpinning of COVID-19.
Open Biology ( IF 5.8 ) Pub Date : 2020-08-27 , DOI: 10.1098/rsob.200208
Vanessa Wazny 1 , Anthony Siau 1 , Kan Xing Wu 1 , Christine Cheung 1, 2
Affiliation  

COVID-19 management guidelines have largely attributed critically ill patients who develop acute respiratory distress syndrome, to a systemic overproduction of pro-inflammatory cytokines. Cardiovascular dysfunction may also represent a primary phenomenon, with increasing data suggesting that severe COVID-19 reflects a confluence of vascular dysfunction, thrombosis and dysregulated inflammation. Here, we first consolidate the information on localized microvascular inflammation and disordered cytokine release, triggering vessel permeability and prothrombotic conditions that play a central role in perpetuating the pathogenic COVID-19 cascade. Secondly, we seek to clarify the gateways which SARS-CoV-2, the causative COVID-19 virus, uses to enter host vascular cells. Post-mortem examinations of patients' tissues have confirmed direct viral endothelial infection within several organs. While there have been advances in single-cell RNA sequencing, endothelial cells across various vascular beds express low or undetectable levels of those touted SARS-CoV-2 entry factors. Emerging studies postulate alternative pathways and the apicobasal distribution of host cell surface factors could influence endothelial SARS-CoV-2 entry and replication. Finally, we provide experimental considerations such as endothelial polarity, cellular heterogeneity in organoids and shear stress dynamics in designing cellular models to facilitate research on viral-induced endothelial dysfunctions. Understanding the vascular underpinning of COVID-19 pathogenesis is crucial to managing outcomes and mortality.



中文翻译:

COVID-19 的血管基础。

COVID-19 管理指南在很大程度上将出现急性呼吸窘迫综合征的危重患者归因于全身促炎细胞因子的过量产生。心血管功能障碍也可能是一种主要现象,越来越多的数据表明,严重的 COVID-19 反映了血管功能障碍、血栓形成和炎症失调的综合作用。在这里,我们首先整合了有关局部微血管炎症和细胞因子释放紊乱的信息,触发血管通透性和血栓形成条件,这些条件在致病性 COVID-19 级联的延续中发挥着核心作用。其次,我们试图阐明 SARS-CoV-2(致病性 COVID-19 病毒)进入宿主血管细胞的途径。对患者组织的尸检已证实多个器官内存在直接病毒内皮感染。尽管单细胞 RNA 测序取得了进展,但各种血管床的内皮细胞表达的 SARS-CoV-2 进入因子水平较低或无法检测到。新兴研究假设替代途径和宿主细胞表面因子的顶端基底层分布可能影响内皮 SARS-CoV-2 的进入和复制。最后,我们提供了设计细胞模型时的实验考虑因素,例如内皮极性、类器官中的细胞异质性和剪切应力动力学,以促进病毒诱导的内皮功能障碍的研究。了解 COVID-19 发病机制的血管基础对于管理结果和死亡率至关重要。

更新日期:2020-08-27
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