Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyzed the transcriptomes of 605,904 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observed a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD epithelial cells expressed higher levels of genes linked directly to the efficiency of viral replication and innate immune response. Additionally, we identified basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.

中文翻译：

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慢性肺部疾病与有利于 SARS-CoV-2 进入和严重程度的基因表达程序相关


慢性肺病 (CLD) 患者患严重冠状病毒病 19 (COVID-19) 和预后不良的风险增加。在这里，我们分析了从健康和慢性肺病肺部分离的 605,904 个单细胞的转录组，以确定肺细胞的分子特征，这些特征可能导致慢性肺病患者的 COVID-19 结果更差。我们在对照肺和 CLD 肺中观察到 SARS-CoV-2 进入因子相似的细胞分布和相对表达。 CLD 上皮细胞表达更高水平的基因，这些基因与病毒复制和先天免疫反应的效率直接相关。此外，我们还发现了炎症基因表达程序的基本差异，这些差异强调了 CLD 如何改变病毒暴露于周围肺部时遇到的炎症微环境。我们的研究表明，慢性肺病伴随着细胞类型特异性基因表达程序的变化，这些基因表达程序为肺上皮做好准备并影响对 SARS-CoV-2 感染的先天和适应性免疫反应。