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Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19.
Ziegler, Carly G K; 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, Alex K; Glover, Sarah C; Horwitz, Bruce H; Ordovas-Montanes, Jose.
  • Ziegler CGK; Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Graduate Program in Biophysics, Harvard University, Cambridg
  • Miao VN; Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Insti
  • Owings AH; Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Navia AW; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Tech
  • Tang Y; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA.
  • Bromley JD; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Microbiology, Massachusetts Institute of T
  • Lotfy P; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA.
  • Sloan M; Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Laird H; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Williams HB; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • George M; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Drake RS; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Christian T; Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Parker A; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Sindel CB; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Burger MW; Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Pride Y; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Hasan M; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Abraham GE; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Senitko M; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Robinson TO; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Shalek AK; Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Graduate Program in Biophysics, Harvard University, Cambridg
  • Glover SC; Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: scglover@umc.edu.
  • Horwitz BH; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Division of Emergency Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Program in Immunology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: bruce.horwitz@child
  • Ordovas-Montanes J; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Program in Immunology, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Elect
Cell ; 184(18): 4713-4733.e22, 2021 09 02.
Article in English | MEDLINE | ID: covidwho-1343153
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severity of Illness Index / SARS-CoV-2 / COVID-19 / Immunity Type of study: Cohort study / Observational study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severity of Illness Index / SARS-CoV-2 / COVID-19 / Immunity Type of study: Cohort study / Observational study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Year: 2021 Document Type: Article