严重 COVID-19 中 SARS-CoV-2 感染局部固有免疫力受损。
Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19.
机构信息
Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Cell. 2021 Sep 2;184(18):4713-4733.e22. doi: 10.1016/j.cell.2021.07.023. Epub 2021 Jul 23.
SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain viral pathology to the nasopharynx. Which cells SARS-CoV-2 primarily targets and how infection influences the respiratory epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy and COVID-19 participants. During COVID-19, we observe expansion of secretory, loss of ciliated, and epithelial cell repopulation via deuterosomal cell expansion. In mild and moderate COVID-19, epithelial cells express anti-viral/interferon-responsive genes, while cells in severe COVID-19 have muted anti-viral responses despite equivalent viral loads. SARS-CoV-2 RNA host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1 goblet, and KRT13 "hillock"-like cells, and we identify genes associated with susceptibility, resistance, or infection response. Our study defines protective and detrimental responses to SARS-CoV-2, the direct viral targets of infection, and suggests that failed nasal epithelial anti-viral immunity may underlie and precede severe COVID-19.
SARS-CoV-2 感染可导致严重的呼吸道 COVID-19。然而，许多患者表现出孤立的上呼吸道症状，这表明病毒病理学有可能局限于鼻咽部。SARS-CoV-2 主要针对哪些细胞，感染如何影响呼吸道上皮细胞，这些仍不完全清楚。我们对 58 名健康人和 COVID-19 参与者的鼻咽拭子进行了 scRNA-seq 分析。在 COVID-19 期间，我们观察到分泌细胞扩张，纤毛细胞丢失，通过多核细胞扩张实现上皮细胞再增殖。在轻症和中度 COVID-19 中，上皮细胞表达抗病毒/干扰素反应基因，而在重症 COVID-19 中，尽管病毒载量相当，但细胞的抗病毒反应却减弱。SARS-CoV-2 RNA 宿主靶细胞高度异质，包括发育中的纤毛细胞、干扰素反应性纤毛细胞、AZGP1 杯状细胞和 KRT13“丘状”样细胞，我们确定了与易感性、抗性或感染反应相关的基因。我们的研究定义了对 SARS-CoV-2 的保护和有害反应、感染的直接病毒靶标，并表明鼻上皮抗病毒免疫的失败可能是严重 COVID-19 的基础和前兆。
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