dc.contributor.author | Ziegler, Carly | |
dc.contributor.author | Miao, Vincent N. | |
dc.contributor.author | Owings, Anna H. | |
dc.contributor.author | Navia, Andrew W. | |
dc.contributor.author | Tang, Ying | |
dc.contributor.author | Bromley, Joshua D. | |
dc.contributor.author | Lotfy, Peter | |
dc.contributor.author | Sloan, Meredith | |
dc.contributor.author | Laird, Hannah | |
dc.contributor.author | Williams, Haley B. | |
dc.contributor.author | George, Micayla | |
dc.contributor.author | Drake, Riley S. | |
dc.contributor.author | Christian, Taylor | |
dc.contributor.author | Parker, Adam | |
dc.contributor.author | Sindel, Campbell B. | |
dc.contributor.author | Burger, Molly W. | |
dc.contributor.author | Pride, Yilianys | |
dc.contributor.author | Hasan, Mohammad | |
dc.contributor.author | Abraham, George E. | |
dc.contributor.author | Senitko, Michal | |
dc.contributor.author | Robinson, Tanya O. | |
dc.contributor.author | Shalek, Alexander K | |
dc.contributor.author | Glover, Sarah C. | |
dc.contributor.author | Horwitz, Bruce H. | |
dc.contributor.author | Ordovas-Montanes, Jose | |
dc.date.accessioned | 2021-08-25T16:25:18Z | |
dc.date.available | 2021-08-25T16:25:18Z | |
dc.date.issued | 2021-07 | |
dc.date.submitted | 2021-05 | |
dc.identifier.issn | 0092-8674 | |
dc.identifier.uri | https://hdl.handle.net/1721.1/131202 | |
dc.description.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. | en_US |
dc.publisher | Elsevier BV | en_US |
dc.relation.isversionof | https://dx.doi.org/10.1016/j.cell.2021.07.023 | en_US |
dc.rights | Creative Commons Attribution 4.0 International license | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_US |
dc.source | Elsevier | en_US |
dc.title | Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19 | en_US |
dc.type | Article | en_US |
dc.identifier.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 | en_US |
dc.contributor.department | Harvard University--MIT Division of Health Sciences and Technology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Institute for Medical Engineering & Science | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemistry | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Microbiology Graduate Program | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.relation.journal | Cell | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.date.submission | 2021-08-13T11:53:31Z | |
mit.license | PUBLISHER_CC | |
mit.metadata.status | Complete | |