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

Tsuguhisa Nakayama1,2, Ivan T Lee1,3,4, Sizun Jiang4,5

  • 1Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.

Cell Reports. Medicine
|October 4, 2021
PubMed

Insights

This study reveals SARS-CoV-2 tropism in head and neck tissues, with higher infection in smokers linked to lower interferon levels. Understanding viral entry factors like ACE2 and TMPRSS2 is key to reducing COVID-19 spread and severity.

Area of Science:

  • Virology
  • Respiratory Medicine
  • Immunology

Background:

  • Understanding SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) viral tropism is crucial for controlling COVID-19 (coronavirus disease 2019) transmission and severity.
  • Limited knowledge exists regarding SARS-CoV-2 infection and replication selectivity in human head, neck, and proximal airway tissues.
  • Key viral entry factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), play a role in SARS-CoV-2 infection.

Purpose of the Study:

  • To investigate SARS-CoV-2 tropism across various mucosal tissues in the human head and neck region and proximal respiratory tract.
  • To identify variations in ACE2 and TMPRSS2 expression in these tissues and their correlation with viral infection.
  • To explore the association between smoking and SARS-CoV-2 infection susceptibility and severity in the proximal airway.

Main Methods:

  • Translational research study examining mucosal tissue samples from the human head and neck and proximal respiratory tract.
  • Analysis of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) expression levels.
  • Detection and quantification of SARS-CoV-2 infection in tissue samples.
  • Assessment of interferon (IFN)-β1 levels in smokers and non-smokers.

Main Results:

  • Significant variability in ACE2 and TMPRSS2 expression was observed among proximal airway mucosal tissues.
  • SARS-CoV-2 infection was detected in all examined head and neck tissues, with pronounced tropism for the nasal cavity and tracheal mucosa.
  • A positive association was found between smoking and increased SARS-CoV-2 viral infection in the proximal airway.
  • Lower interferon (IFN)-β1 levels were noted in smokers compared to non-smokers, potentially explaining increased susceptibility to severe COVID-19.

Conclusions:

  • The study identifies specific tropism of SARS-CoV-2 within the human head and neck and proximal airway, highlighting the nasal cavity and trachea.
  • Variations in ACE2 and TMPRSS2 expression contribute to differential viral susceptibility.
  • Smoking is associated with higher SARS-CoV-2 infection and potentially more severe COVID-19 outcomes, possibly due to altered interferon responses.
Keywords:
ACE2COVID-19IFN-β1SARS-CoV-2TMPRSS2ciliated epithelial cellnasal cavitysmokingtracheaupper airway

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