Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19
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1-s2.0-S0092867421008825-main.pdf
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26.03 MB
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Checksum (MD5)
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Author(s)
Ziegler, Carly
Miao, Vincent N.
Owings, Anna H.
Navia, Andrew W.
Tang, Ying
Bromley, Joshua D.
Lotfy, Peter
Sloan, Meredith
Laird, Hannah
Williams, Haley B.
Date Issued
July 2021
Journal
Cell
Publisher
Elsevier BV
Citation
Ziegler, Carly G.K. et al. "Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19." Cell (July 2021): 10.1016/j.cell.2021.07.023. © 2021 The Authors
Version
Final published version
Abstract
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, 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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Microbiology Graduate Program
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/j.cell.2021.07.023
