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Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.
- Source :
-
Cell reports. Medicine [Cell Rep Med] 2021 Oct 19; Vol. 2 (10), pp. 100421. Date of Electronic Publication: 2021 Sep 28. - Publication Year :
- 2021
-
Abstract
- 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.<br />Competing Interests: I.T.L. is currently an employee and shareholder of Moderna, although this work was conducted prior to/independent of his employment. I.T.L. had also received research support unrelated to this study from Genentech (Roche). Moderna did not fund or participate in this study in any form.<br /> (© 2021.)
- Subjects :
- Aged
Aged, 80 and over
COVID-19 genetics
COVID-19 metabolism
Female
Gene Expression Regulation
Humans
Male
Middle Aged
Nasal Cavity metabolism
SARS-CoV-2 physiology
Trachea metabolism
Angiotensin-Converting Enzyme 2 genetics
COVID-19 transmission
Respiratory Mucosa metabolism
Serine Endopeptidases genetics
Smokers
Viral Tropism
Subjects
Details
- Language :
- English
- ISSN :
- 2666-3791
- Volume :
- 2
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell reports. Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 34604819
- Full Text :
- https://doi.org/10.1016/j.xcrm.2021.100421