Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19
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 epitheli...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/131202 |
| _version_ | 1826207314276777984 |
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| author | 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 |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology 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 |
| author_sort | Ziegler, Carly |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:47:45Z |
| format | Article |
| id | mit-1721.1/131202 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T13:47:45Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1312022022-10-01T17:11:40Z Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19 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 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 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. 2021-08-25T16:25:18Z 2021-08-25T16:25:18Z 2021-07 2021-05 Article http://purl.org/eprint/type/JournalArticle 0092-8674 https://hdl.handle.net/1721.1/131202 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 https://dx.doi.org/10.1016/j.cell.2021.07.023 Cell Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | 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 Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19 |
| title | Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19 |
| title_full | Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19 |
| title_fullStr | Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19 |
| title_full_unstemmed | Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19 |
| title_short | Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19 |
| title_sort | impaired local intrinsic immunity to sars cov 2 infection in severe covid 19 |
| url | https://hdl.handle.net/1721.1/131202 |
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