Faculty Stanford University School of Medicine Stanford University School of Medicine Stanford, California
Introduction: Understanding viral tropism is essential towards reducing SARS-CoV-2 transmission, decreasing mortality from COVID-19, and limiting the rise of mutant strains. Little is known about the extent to which distinct tissue sites in the proximal respiratory tract selectively permit SARS-CoV-2 infection and replication.
Methods: The expression of SARS-CoV-2 entry factors, ACE2 and TMPRSS2, was compared across various control human proximal airway mucosal tissues. Intracellular levels of SARS-CoV-2 viral infection in head & neck mucosal tissues from deceased COVID-19 patients was analyzed over an array of distinct head and neck tissue sites. Finally, clinical characteristics of COVID-19 patients, such as smoking status, were assessed.
Results: ACE2 and TMPRSS2 expression were elevated in the trachea/bronchus compared to the nasopharynx, oro/hypopharynx, and conjunctiva (p < 0.05 and p<0.01 respectively). SARS-CoV-2 RNA was detected significantly more in the nasal and tracheal epithelia compared to other sites, with respect to both infected surface area and copies of RNA within the infected area (p < 0.05). SARS-CoV-2 RNA levels were significantly higher amongst smokers (both current and former) compared to non-smokers (p < 0.01), with downregulation of IFN-beta1 as a potential mechanism for increased SARS-CoV-2 infection in smokers.
Conclusion: We discover key variabilities in the expression of ACE2 and TMPRSS2 in the mucosal tissues of the human proximal airways. SARS-CoV-2 infection has notable and measurable tropism for the nasal cavity and tracheal mucosa. Smoking is associated with higher SARS-CoV-2 viral infection in the human proximal airway, and increased susceptibility to developing severe COVID-19.