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  • Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.

Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.

Cell reports. Medicine (2021-10-05)
Tsuguhisa Nakayama, Ivan T Lee, Sizun Jiang, Matthias S Matter, Carol H Yan, Jonathan B Overdevest, Chien-Ting Wu, Yury Goltsev, Liang-Chun Shih, Chun-Kang Liao, Bokai Zhu, Yunhao Bai, Peter Lidsky, Yinghong Xiao, David Zarabanda, Angela Yang, Meena Easwaran, Christian M Schürch, Pauline Chu, Han Chen, Anna K Stalder, David R McIlwain, Nicole A Borchard, Phillip A Gall, Sachi S Dholakia, Wei Le, Le Xu, Chih-Jaan Tai, Te-Huei Yeh, Elizabeth Erickson-Direnzo, Jason M Duran, Kirsten D Mertz, Peter H Hwang, Jasmin D Haslbauer, Peter K Jackson, Thomas Menter, Raul Andino, Peter D Canoll, Adam S DeConde, Zara M Patel, Alexandar Tzankov, Garry P Nolan, Jayakar V Nayak
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-TMPRSS2 Antibody, clone P5H9-A3, clone P5H9-A3, from mouse
Sigma-Aldrich
Phalloidin–Atto 647N, BioReagent, suitable for fluorescence, ≥80% (HPLC)