학술논문
Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19.
Document Type
Article
Author
Ziegler, Carly G.K.; 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 III, George E.; Senitko, Michal
Source
Subject
*COVID-19
*SARS-CoV-2
*VIRAL tropism
*NASAL mucosa
*VIRUS diseases
*EPITHELIAL cells
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Language
ISSN
0092-8674
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, 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. [Display omitted] • scRNA-seq on nasopharyngeal swabs of 58 COVID-19 and healthy participants • SARS-CoV-2 induces ciliated cell loss with secretory and deuterosomal expansion • Early, muted anti-viral responses in nasal epithelia in severe COVID-19 • Host-virus co-detection maps cell tropism and intrinsic responses to SARS-CoV-2 A study of nasopharyngeal swabs from healthy and COVID-19-infected individuals shows how infection leads to compositional changes in the respiratory epithelium, with early dampened antiviral responses in the nasal epithelia likely underlying and preceding severe disease. [ABSTRACT FROM AUTHOR]