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

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

doi:10.1016/j.xcrm.2021.100421

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

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 ChenAnna 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^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

23 Citations (Scopus)

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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. © 2021

Original language	English
Article number	100421
Journal	Cell Reports Medicine
Volume	2
Issue number	10
Online published	28 Sept 2021
DOIs	https://doi.org/10.1016/j.xcrm.2021.100421
Publication status	Published - 19 Oct 2021
Externally published	Yes

Research Keywords

ACE2
ciliated epithelial cell
COVID-19
IFN-β1
nasal cavity
SARS-CoV-2
smoking
TMPRSS2
trachea
upper airway

Publisher's Copyright Statement

This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.xcrm.2021.100421

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Nakayama, T., Lee, I. T., Jiang, S., Matter, M. S., Yan, C. H., Overdevest, J. B., Wu, C.-T., Goltsev, Y., Shih, L.-C., Liao, C.-K., Zhu, B., Bai, Y., Lidsky, P., Xiao, Y., Zarabanda, D., Yang, A., Easwaran, M., Schürch, C. M., Chu, P., ... Nayak, J. V. (2021). Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers. Cell Reports Medicine, 2(10), Article 100421. https://doi.org/10.1016/j.xcrm.2021.100421

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title = "Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers",

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. {\textcopyright} 2021",

keywords = "ACE2, ciliated epithelial cell, COVID-19, IFN-β1, nasal cavity, SARS-CoV-2, smoking, TMPRSS2, trachea, upper airway",

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

year = "2021",

month = oct,

day = "19",

doi = "10.1016/j.xcrm.2021.100421",

language = "English",

volume = "2",

journal = "Cell Reports Medicine",

issn = "2666-3791",

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Nakayama, T, Lee, IT, Jiang, S, Matter, MS, Yan, CH, Overdevest, JB, Wu, C-T, Goltsev, Y, Shih, L-C, Liao, C-K, Zhu, B, Bai, Y, Lidsky, P, Xiao, Y, Zarabanda, D, Yang, A, Easwaran, M, Schürch, CM, Chu, P, Chen, H, Stalder, AK, McIlwain, DR, Borchard, NA, Gall, PA, Dholakia, SS, Le, W, Xu, L, Tai, C-J, Yeh, T-H, Erickson-Direnzo, E, Duran, JM, Mertz, KD, Hwang, PH, Haslbauer, JD, Jackson, PK, Menter, T, Andino, R, Canoll, PD, DeConde, AS, Patel, ZM, Tzankov, A, Nolan, GP & Nayak, JV 2021, 'Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers', Cell Reports Medicine, vol. 2, no. 10, 100421. https://doi.org/10.1016/j.xcrm.2021.100421

TY - JOUR

T1 - Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers

AU - Nakayama, Tsuguhisa

AU - Lee, Ivan T.

AU - Jiang, Sizun

AU - Matter, Matthias S.

AU - Yan, Carol H.

AU - Overdevest, Jonathan B.

AU - Wu, Chien-Ting

AU - Goltsev, Yury

AU - Shih, Liang-Chun

AU - Liao, Chun-Kang

AU - Zhu, Bokai

AU - Bai, Yunhao

AU - Lidsky, Peter

AU - Xiao, Yinghong

AU - Zarabanda, David

AU - Yang, Angela

AU - Easwaran, Meena

AU - Schürch, Christian M.

AU - Chu, Pauline

AU - Chen, Han

AU - Stalder, Anna K.

AU - McIlwain, David R.

AU - Borchard, Nicole A.

AU - Gall, Phillip A.

AU - Dholakia, Sachi S.

AU - Le, Wei

AU - Xu, Le

AU - Tai, Chih-Jaan

AU - Yeh, Te-Huei

AU - Erickson-Direnzo, Elizabeth

AU - Duran, Jason M.

AU - Mertz, Kirsten D.

AU - Hwang, Peter H.

AU - Haslbauer, Jasmin D.

AU - Jackson, Peter K.

AU - Menter, Thomas

AU - Andino, Raul

AU - Canoll, Peter D.

AU - DeConde, Adam S.

AU - Patel, Zara M.

AU - Tzankov, Alexandar

AU - Nolan, Garry P.

AU - Nayak, Jayakar V.

PY - 2021/10/19

Y1 - 2021/10/19

N2 - 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. © 2021

AB - 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. © 2021

KW - ACE2

KW - ciliated epithelial cell

KW - COVID-19

KW - IFN-β1

KW - nasal cavity

KW - SARS-CoV-2

KW - smoking

KW - TMPRSS2

KW - trachea

KW - upper airway

UR - http://www.scopus.com/inward/record.url?scp=85116801681&partnerID=8YFLogxK

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85116801681&origin=recordpage

U2 - 10.1016/j.xcrm.2021.100421

DO - 10.1016/j.xcrm.2021.100421

M3 - RGC 21 - Publication in refereed journal

C2 - 34604819

SN - 2666-3791

VL - 2

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 10

M1 - 100421

ER -

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

Abstract

Research Keywords

Publisher's Copyright Statement

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