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 + host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1 high 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 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 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.
【저자키워드】 COVID-19, SARS-CoV-2, Human, interferon, Anti-viral, nasal mucosa, epithelial immunity, correlates of immunity, scRNA-seq, 【초록키워드】 severe COVID-19, SARS-COV-2 infection, susceptibility, Infection, interferon, nasal, Moderate COVID-19, Nasopharyngeal swab, Viral, cells, nasopharyngeal swabs, response, nasopharynx, Mild, target, epithelial cells, cell tropism, SARS-CoV-2 RNA, expansion, respiratory, epithelial, scRNA-seq, Protective, antiviral response, severe disease, detrimental, epithelial cell, leads, target cells, upper respiratory symptoms, Participants, Abstract, ciliated cell, infected individuals, individual, goblet, viral loads, participant, anti-viral response, Express, viral pathology, heterogenous, respiratory epithelium, anti-viral responses, Anti-viral immunity, epithelia, AZGP1, Cell loss, KRT13, secretory, Genes, Cell, observé, intrinsic, identify, performed, healthy, changes in, induce, ciliated, influence, underlie, 【제목키워드】 Immunity, Local, intrinsic, Impaired,