论文
论文标题：Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19
作者：Carly G.K. Ziegler, Vincent N. Miao, Anna H. Owings, Andrew W. Navia, Ying Tang, Joshua D. Bromley, Peter Lotfy, Meredith Sloan, Hannah Laird, Haley B. Williams, Micayla George, Riley S. Drake, Taylor Christian, Adam Parker, Campbell B. Sindel, Molly W. Burger, Yilianys Pride, Mohammad Hasan, Jose Ordovas-Montanes
期刊：Cell
发表时间：2021/07/23
数字识别码：10.1016/j.cell.2021.07.023
摘要：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 expansion. In mild/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, AZGP1high 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.
