ABSTRACT
For new principal investigators, the first years are key to getting a laboratory off the ground and running. COVID-19 has changed the world, bringing on unforeseen difficulties and challenges at every level. We asked these investigators to share their experiences in navigating the unique environment since the start of the pandemic-what has changed in their vision for their laboratory, how they have adapted, and what advice they can share with others in a similar situation.
Subject(s)
COVID-19/epidemiology , Laboratories , Adaptation, Psychological , Biomedical Research/trends , COVID-19/psychology , Communication , Humans , Laboratories/trends , Laboratory Personnel/psychology , Laboratory Personnel/trends , SARS-CoV-2ABSTRACT
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.