  The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19
coronavirus disease, is a global threat. To better understand viral tropism, we
assessed the RNA expression of the coronavirus receptor, ACE2, as well as the
viral S protein priming protease TMPRSS2 thought to govern viral entry in
single-cell RNA-sequencing (scRNA-seq) datasets from healthy individuals
generated by the Human Cell Atlas consortium. We found that ACE2, as well as
the protease TMPRSS2, are differentially expressed in respiratory and gut
epithelial cells. In-depth analysis of epithelial cells in the respiratory tree
reveals that nasal epithelial cells, specifically goblet/secretory cells and
ciliated cells, display the highest ACE2 expression of all the epithelial cells
analyzed. The skewed expression of viral receptors/entry-associated proteins
towards the upper airway may be correlated with enhanced transmissivity.
Finally, we showed that many of the top genes associated with ACE2 airway
epithelial expression are innate immune-associated, antiviral genes, highly
enriched in the nasal epithelial cells. This association with immune pathways
might have clinical implications for the course of infection and viral
pathology, and highlights the specific significance of nasal epithelia in viral
infection. Our findings underscore the importance of the availability of the
Human Cell Atlas as a reference dataset. In this instance, analysis of the
compendium of data points to a particularly relevant role for nasal goblet and
ciliated cells as early viral targets and potential reservoirs of SARS-CoV-2
infection. This, in turn, serves as a biological framework for dissecting viral
transmission and developing clinical strategies for prevention and therapy.
