Summary Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers. Graphical abstract Highlights • ACE2 and TMPRSS2 are variably expressed among mucosal surfaces of the head and neck • Enriched TMPRSS2 expression may drive SARS-CoV-2 tropism for the nasal cavity and trachea • SARS-CoV-2 preferentially replicates in the nasal cavity and trachea of individuals with COVID-19 • Smoking is associated with increased proximal airway SARS-CoV-2, in part because of IFN-β1 Nakayama et al. discover key variabilities in expression of SARS-CoV-2 entry factors among human head and neck mucosal tissues. They demonstrate that SARS-CoV-2 preferentially infects the nasal cavity and trachea. They uncover an association between smoking and higher SARS-CoV-2 in the human proximal airway, in part because of differences in IFN-β1 expression.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, smoking, upper airway, Nasal cavity, Trachea, ciliated epithelial cell, IFN-β1, TMPRSS2,