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Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.
Nakayama, Tsuguhisa; Lee, Ivan T; Jiang, Sizun; Matter, Matthias S; Yan, Carol H; Overdevest, Jonathan B; Wu, Chien-Ting; Goltsev, Yury; Shih, Liang-Chun; Liao, Chun-Kang; Zhu, Bokai; Bai, Yunhao; Lidsky, Peter; Xiao, Yinghong; Zarabanda, David; Yang, Angela; Easwaran, Meena; Schürch, Christian M; Chu, Pauline; Chen, Han; Stalder, Anna K; McIlwain, David R; Borchard, Nicole A; Gall, Phillip A; Dholakia, Sachi S; Le, Wei; Xu, Le; Tai, Chih-Jaan; Yeh, Te-Huei; Erickson-Direnzo, Elizabeth; Duran, Jason M; Mertz, Kirsten D; Hwang, Peter H; Haslbauer, Jasmin D; Jackson, Peter K; Menter, Thomas; Andino, Raul; Canoll, Peter D; DeConde, Adam S; Patel, Zara M; Tzankov, Alexandar; Nolan, Garry P; Nayak, Jayakar V.
  • Nakayama T; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • Lee IT; Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan.
  • Jiang S; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • Matter MS; Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Yan CH; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Overdevest JB; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Wu CT; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Goltsev Y; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Shih LC; 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.
  • Liao CK; Department of Otolaryngology-Head and Neck Surgery, Columbia University School of Medicine, New York, NY, USA.
  • Zhu B; Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Bai Y; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Lidsky P; Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
  • Xiao Y; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
  • Zarabanda D; Terry Fox Cancer Research Laboratory, Translational Medicine Center, China Medical University Hospital, Taichung, Taiwan.
  • Yang A; Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
  • Easwaran M; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Schürch CM; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Chu P; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Chen H; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Stalder AK; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • McIlwain DR; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • Borchard NA; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • Gall PA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Dholakia SS; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Le W; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Xu L; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Tai CJ; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Yeh TH; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • Erickson-Direnzo E; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • Duran JM; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • Mertz KD; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • Hwang PH; Department of Pediatrics, University of California San Diego School of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Haslbauer JD; Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
  • Jackson PK; School of Medicine, China Medical University, Taichung, Taiwan.
  • Menter T; Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
  • Andino R; Department of Otolaryngology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Canoll PD; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • DeConde AS; Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego School of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Patel ZM; Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
  • Tzankov A; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.
  • Nolan GP; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Nayak JV; Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Cell Rep Med ; 2(10): 100421, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1440413
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)-ß1 levels between smokers and non-smokers.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Respiratory Mucosa / Viral Tropism / Smokers / Angiotensin-Converting Enzyme 2 / COVID-19 Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Rep Med Year: 2021 Document Type: Article Affiliation country: J.xcrm.2021.100421

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Respiratory Mucosa / Viral Tropism / Smokers / Angiotensin-Converting Enzyme 2 / COVID-19 Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Rep Med Year: 2021 Document Type: Article Affiliation country: J.xcrm.2021.100421