Endothelialitis, Microischemia, and Intussusceptive Angiogenesis in COVID-19
Endothelialitis, Microischemia, and Intussusceptive Angiogenesis in COVID-19
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DOI：
10.1101/cshperspect.a041157
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发表时间：
2022-10-01
影响因子：
5.4
通讯作者：
Jonigk, Danny
中科院分区：
文献类型：
--
作者：
Mentzer, Steven J.;Ackermann, Maximilian;Jonigk, Danny
新冠肺炎与一系列疾病严重程度有关--从最轻微的症状到危及生命的多系统器官衰竭。严重的新冠肺炎似乎与疾病的血管中心期或血管期有关。在研究死于新冠肺炎的尸检患者时，我们发现新冠肺炎患者中肺泡毛细血管微血栓的发生率是同类流感患者的9倍。新冠肺炎微循环的腐蚀铸型显示微血管扭曲，支气管循环增强，肠套叠血管生成显著增加。在重度新冠肺炎患者中，内皮细胞通常表现出明显的超微结构损伤。高分辨率成像显示，微循环障碍与肺(次级小叶)微解剖间隔的缺血性改变有关。对这些区域的纳米线分析已经证实了一个与微缺血兼容的转录签名。我们得出结论，不可逆转的组织缺血为与长途新冠肺炎症状相关的囊性和纤维性改变提供了一种解释。
COVID-19 has been associated with a range of illness severity-from minimal symptoms to life-threatening multisystem organ failure. The severe forms of COVID-19 appear to be associated with an angiocentric or vascular phase of the disease. In studying autopsy patients succumbing to COVID-19, we found alveolar capillary microthrombi were 9 times more common in COVID-19 than in comparable patients with influenza. Corrosion casting of the COVID-19 microcirculation has revealed microvascular distortion, enhanced bronchial circulation, and striking increases in intussusceptive angiogenesis. In patients with severe COVID-19, endothelial cells commonly demonstrate significant ultrastructural injury. High-resolution imaging suggests that microcirculation perturbations are linked to ischemic changes in microanatomic compartments of the lung (secondary lobules). NanoString profiling of these regions has confirmed a transcriptional signature compatible with microischemia. We conclude that irreversible tissue ischemia provides an explanation for the cystic and fibrotic changes associated with long-haul COVID-19 symptoms.