COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis
COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis
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DOI：
10.1038/s41587-020-0602-4
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发表时间：
2020-06-26
影响因子：
46.9
通讯作者：
Eils, Roland
中科院分区：
文献类型：
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作者：
Chua, Robert Lorenz;Lukassen, Soeren;Eils, Roland
对 COVID-19 患者样本的单细胞分析可识别与严重疾病相关的激活的免疫通路。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 19 名临床特征明确的中度或危重疾病患者以及 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，危重病例表现出上皮细胞和免疫细胞之间更强的相互作用，如配体受体表达谱所示，以及激活的免疫细胞，包括表达CCL2、CCL3、CCL20、CXCL1、CXCL3、CXCL10、IL8、IL1BandTNF的炎性巨噬细胞。与中度病例相比，危重病例的转录差异可能导致临床观察到炎症组织损伤、肺损伤和呼吸衰竭加剧。我们的数据表明，CCR1 和/或 CCR5 通路的药物抑制可能会抑制危重 COVID-19 中的免疫过度激活。
Single-cell analysis of COVID-19 patient samples identifies activated immune pathways that correlate with severe disease.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 receptorACE2, 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 expressingCCL2,CCL3,CCL20,CXCL1,CXCL3,CXCL10,IL8,IL1BandTNF. 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.