期刊
CELL
卷 184, 期 18, 页码 4713-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2021.07.023
关键词
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资金
- Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation [2020-216949]
- Richard and Susan Smith Family Foundation
- AGA Research Foundation's AGA-Takeda Pharmaceuticals Research Scholar Award in IBD [AGA2020-13-01]
- Food Allergy Science Initiative
- New York Stem Cell Foundation
- NIH [DK122532-01A1, T32GM007753, 5T32AG000222, 5U24AI118672]
- Leona M. and Harry B. Helmsley Charitable Trust [12019PG-CD002]
- Crohn's and Colitis Foundation [54518]
- Ludwig Center for Molecular Oncology at MIT
- Bill and Melinda Gates Foundation
- Sloan Fellowship in Chemistry
- Ragon Institute of MGH, MIT and Harvard
Our study reveals the diverse responses of cells in the nasopharyngeal epithelium to SARS-CoV-2 infection, with different gene expression profiles observed in mild, moderate, and severe cases of COVID-19. The identification of specific cell types and associated genes highlights the complexity of the host response to viral infection, and suggests that impaired nasal epithelial anti-viral immunity may contribute to the development of severe COVID-19.
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(high) 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.
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