Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19
| Autor: | Meredith Sloan, Jose Ordovas-Montanes, Molly W. Burger, Carly G. K. Ziegler, Sarah C. Glover, Joshua D. Bromley, Taylor Christian, Alex K. Shalek, Bruce H. Horwitz, Andrew W. Navia, Yilianys Pride, Anna H. Owings, Hannah Laird, Haley B. Williams, Peter Lotfy, Micayla George, Adam M. Parker, Vincent N. Miao, Michal Senitko, Ying Tang, Tanya O. Robinson, Campbell B Sindel, Riley S. Drake, Mohammad H. Hasan, George E. Abraham |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male anti-viral Intrinsic immunity nasal mucosa Cell type Myeloid Transcription Genetic viruses epithelial immunity Mucous membrane of nose Respiratory Mucosa Biology Severity of Illness Index General Biochemistry Genetics and Molecular Biology Article Virus Cohort Studies Interferon Immunity Nasopharynx scRNA-seq medicine Humans human Respiratory system correlates of immunity Aged SARS-CoV-2 COVID-19 Bystander Effect interferon Middle Aged Viral Load Epithelium medicine.anatomical_structure Immunology RNA Viral Respiratory epithelium Female Viral load medicine.drug |
| Zdroj: | Cell bioRxiv article-version (status) pre article-version (number) 1 |
| Popis: | 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. Graphical abstract 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. |
| Databáze: | OpenAIRE |
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