Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19.

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From: Cell(Vol. 184, Issue 18)
Publisher: Elsevier B.V.
Document Type: Report
Length: 550 words

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Keywords SARS-CoV-2; COVID-19; human; nasal mucosa; epithelial immunity; correlates of immunity; interferon; anti-viral; scRNA-seq Highlights * 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 Summary 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.sup.+ host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1.sup.high goblet, and KRT13.sup.+ "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. Author Affiliation: (1) Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA 02115, USA (2) Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA (3) Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA (4) Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, USA (5) Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA (6) Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA (7) Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA (8) Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA (9) Department of Microbiology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA (10) Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA (11) Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA (12) Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS 39216, USA (13) Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA (14) Division of Emergency Medicine, Boston Children's Hospital, Boston, MA 02115, USA (15) Program in Immunology, Harvard Medical School, Boston, MA 02115, USA (16) Harvard Stem Cell Institute, Cambridge, MA 02138, USA * Corresponding author Article History: Received 16 February 2021; Revised 24 May 2021; Accepted 14 July 2021 (miscellaneous) Published: July 23, 2021 (footnote)17 These authors contributed equally (footnote)18 Senior author (footnote)19 Lead contact Byline: Carly G.K. Ziegler (1,2,3,4,5,17), Vincent N. Miao (1,2,3,5,17), Anna H. Owings (6,17), Andrew W. Navia (2,3,5,7,17), Ying Tang (8,17), Joshua D. Bromley (2,3,5,9,17), Peter Lotfy (3,8), Meredith Sloan (6), Hannah Laird (10), Haley B. Williams (10), Micayla George (2,3,5), Riley S. Drake (2,3,5), Taylor Christian (6), Adam Parker (10), Campbell B. Sindel (11), Molly W. Burger (12), Yilianys Pride (10), Mohammad Hasan (10), George E. Abraham III (11), Michal Senitko (11), Tanya O. Robinson (10), Alex K. Shalek [shalek@mit.edu] (1,2,3,4,5,7,13,15,16,18,*), Sarah C. Glover [scglover@umc.edu] (10,18,**), Bruce H. Horwitz [bruce.horwitz@childrens.harvard.edu] (8,14,15,18,***), Jose Ordovas-Montanes [jose.ordovas-montanes@childrens.harvard.edu] (3,8,15,16,18,19,****)

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Gale Document Number: GALE|A674141563