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COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis.
Nature Biotechnology ( IF 46.9 ) Pub Date : 2020-06-26 , DOI: 10.1038/s41587-020-0602-4
Robert Lorenz Chua 1 , Soeren Lukassen 1 , Saskia Trump 2 , Bianca P Hennig 1 , Daniel Wendisch 3 , Fabian Pott 4, 5 , Olivia Debnath 1 , Loreen Thürmann 2 , Florian Kurth 3, 6 , Maria Theresa Völker 7 , Julia Kazmierski 4, 5 , Bernd Timmermann 8 , Sven Twardziok 1 , Stefan Schneider 1 , Felix Machleidt 3 , Holger Müller-Redetzky 3 , Melanie Maier 9 , Alexander Krannich 10 , Sein Schmidt 10 , Felix Balzer 11 , Johannes Liebig 1 , Jennifer Loske 2 , Norbert Suttorp 3, 12 , Jürgen Eils 1 , Naveed Ishaque 1 , Uwe Gerd Liebert 9 , Christof von Kalle 10 , Andreas Hocke 3 , Martin Witzenrath 3, 12 , Christine Goffinet 4, 5 , Christian Drosten 4 , Sven Laudi 7 , Irina Lehmann 2, 12 , Christian Conrad 1 , Leif-Erik Sander 3 , Roland Eils 1, 12, 13
Affiliation  

To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.



中文翻译:

COVID-19 的严重程度与通过单细胞分析确定的气道上皮-免疫细胞相互作用相关。

为了研究与 2019 年严重冠状病毒病 (COVID-19) 相关的免疫反应和机制,我们对来自 19 名临床特征良好的中度或危重疾病患者和 5 名健康对照者的鼻咽和支气管样本进行了单细胞 RNA 测序。我们确定了易受严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染的气道上皮细胞类型和状态。在 COVID-19 患者中,上皮细胞的 SARS-CoV-2 进入受体ACE2的表达平均增加了三倍,这与免疫细胞的干扰素信号相关。与中度病例相比,危重病例表现出更强的上皮细胞和免疫细胞之间的相互作用,如配体-受体表达谱所示,以及激活的免疫细胞,包括表达CCL2CCL3CCL20CXCL1CXCL3CXCL10IL8IL1B肿瘤坏死因子. 与中度病例相比,危重病例的转录差异可能导致炎症组织损伤、肺损伤和呼吸衰竭加剧的临床观察。我们的数据表明,对 CCR1 和/或 CCR5 通路的药理学抑制可能会抑制关键 COVID-19 中的免疫过度激活。

更新日期:2020-06-26
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