Cell Reports Medicine (Oct 2021)
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
Affiliations
- Tsuguhisa Nakayama
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA; Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan
- Ivan T. Lee
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA; Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Corresponding author
- Sizun Jiang
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Matthias S. Matter
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
- Carol H. Yan
- Division of Otolaryngology – Head and Neck Surgery, Department of Surgery, University of California San Diego School of Medicine, University of California, San Diego, La Jolla, CA, USA
- Jonathan B. Overdevest
- Department of Otolaryngology–Head and Neck Surgery, Columbia University School of Medicine, New York, NY, USA
- Chien-Ting Wu
- Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA
- Yury Goltsev
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
- Liang-Chun Shih
- Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Terry Fox Cancer Research Laboratory, Translational Medicine Center, China Medical University Hospital, Taichung, Taiwan
- Chun-Kang Liao
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
- Bokai Zhu
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
- Yunhao Bai
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
- Peter Lidsky
- Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA
- Yinghong Xiao
- Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA
- David Zarabanda
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
- Angela Yang
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
- Meena Easwaran
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
- Christian M. Schürch
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
- Pauline Chu
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
- Han Chen
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
- Anna K. Stalder
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
- David R. McIlwain
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
- Nicole A. Borchard
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
- Phillip A. Gall
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
- Sachi S. Dholakia
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
- Wei Le
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
- Le Xu
- Department of Pediatrics, University of California San Diego School of Medicine, University of California, San Diego, La Jolla, CA, USA
- Chih-Jaan Tai
- Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan
- Te-Huei Yeh
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Department of Otolaryngology, College of Medicine, National Taiwan University, Taipei, Taiwan
- Elizabeth Erickson-Direnzo
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
- Jason M. Duran
- Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego School of Medicine, University of California, San Diego, La Jolla, CA, USA
- Kirsten D. Mertz
- Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland
- Peter H. Hwang
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
- Jasmin D. Haslbauer
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
- Peter K. Jackson
- Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA
- Thomas Menter
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
- Raul Andino
- Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA
- Peter D. Canoll
- Department of Pathology and Cell Biology, Columbia University Medical Center, Irving Cancer Research Center, New York, NY, USA
- Adam S. DeConde
- Division of Otolaryngology – Head and Neck Surgery, Department of Surgery, University of California San Diego School of Medicine, University of California, San Diego, La Jolla, CA, USA
- Zara M. Patel
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
- Alexandar Tzankov
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; Corresponding author
- Garry P. Nolan
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Corresponding author
- Jayakar V. Nayak
- Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA; Department of Otolaryngology – Head and Neck Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Corresponding author
- Journal volume & issue
-
Vol. 2,
no. 10
p. 100421
Abstract
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.
