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

  • Biology
  • Cell Atlas
  • Computational Methods
  • Genomics
  • Immunology
  • Infectious Disease
  • Carly Ziegler
  • Vincent Miao
  • Andrew Navia
  • Josh Bromley
  • Micayla George
  • Riley Drake
  • Alex K. Shalek
  • José Ordovas-Montañes
  • Ziegler et al.▾
    Ziegler, C.G.K.*, Miao, V.N.*, Owings, A.H.*, Navia, A.W.*, Tang, Y.*, Bromley, J.D.*, Lotfy, P., Sloan, M., Laird, H., Williams, H.B., 10, George, M., Drake, R.S., Christian, T., 6, Parker, A., Sindel, C.B., Burger, M.W., Pride, Y., Hasan, M., Abraham III, G.E., Senitko, M., Robinson, T.O., Shalek, A.K.#, Glover, S.C.#, Horwitz, B.H.#, Ordovas-Montanes, J.,
  • Cell
  • July, 2021
Biology
Cell Atlas
Computational Methods
Genomics
Immunology
Infectious Disease
Carly Ziegler
Vincent Miao
Andrew Navia
Josh Bromley
Micayla George
Riley Drake
Alex K. Shalek
José Ordovas-Montañes

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 expansion. In mild/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.

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