Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19
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.; George, Micayla; Drake, Riley S.; Christian, Taylor; Parker, Adam; Sindel, Campbell B.; Burger, Molly W.; Pride, Yilianys; Hasan, Mohammad; Abraham, George E.; Senitko, Michal; Robinson, Tanya O.; Shalek, Alexander K; Glover, Sarah C.; Horwitz, Bruce H.; Ordovas-Montanes, Jose; ... Show more Show less![Thumbnail](/bitstream/handle/1721.1/131202/1-s2.0-S0092867421008825-main.pdf.jpg?sequence=3&isAllowed=y)
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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.
Date issued
2021-07Department
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 MITJournal
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
ISSN
0092-8674