"Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19". Ziegler et al.

Published: 23 June 2021| Version 1 | DOI: 10.17632/pjr7b8sbf8.1
Carly Ziegler, Vincent Miao, Anna Owings, Andrew Navia, Ying Tang, Joshua Bromley, Peter Lotfy, Meredith Sloan, Hannah Laird, Haley Williams, Micayla George, Riley Drake, Taylor Christian, Adam Parker, Campbell Sindel, Molly Burger, Yilianys Pride, Mohammad Hasan, George Abraham, Michal Senitko, Tanya Robinson, Alex Shalek, Sarah Glover, Bruce Horwitz, Jose Ordovas-Montanes


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 are the primary targets of SARS-CoV-2 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 likely involved in susceptibility, resistance, or response to infection. We define protective and detrimental responses to SARS-CoV-2, the direct viral targets of infection, and suggest that failed epithelial anti-viral immunity may underlie severe COVID-19.



Systems Biology, Transcriptomics, Respiratory Epithelium, Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19