Smoking increases expression of the SARS-CoV-2 spike protein-binding long ACE2 isoform in bronchial epithelium

Simon D. Pouwels, Maarten van den Berge, Gwenda F. Vasse, Wim Timens, Corry Anke Brandsma, Hananeh Aliee, Pieter S. Hiemstra, Victor Guryev, Alen Faiz*

*Corresponding author for this work

Research output: Contribution to journalLetterAcademicpeer-review

2 Citations (Scopus)
36 Downloads (Pure)

Abstract

After more than two years the COVID-19 pandemic, that is caused by infection with the respiratory SARS-CoV-2 virus, is still ongoing. The risk to develop severe COVID-19 upon SARS-CoV-2 infection is increased in individuals with a high age, high body mass index, and who are smoking. The SARS-CoV-2 virus infects cells of the upper respiratory tract by entering these cells upon binding to the Angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is expressed in various cell types in the lung but the expression is especially high in goblet and ciliated cells. Recently, it was shown that next to its full-length isoform, ACE2 also has a short isoform. The short isoform is unable to bind SARS-CoV-2 and does not facilitate viral entry. In the current study we investigated whether active cigarette smoking increases the expression of the long or the short ACE2 isoform. We showed that in active smokers the expression of the long, active isoform, but not the short isoform of ACE2 is higher compared to never smokers. Additionally, it was shown that the expression of especially the long, active isoform of ACE2 was associated with secretory, club and goblet epithelial cells. This study increases our understanding of why current smokers are more susceptible to SARS-CoV-2 infection, in addition to the already established increased risk to develop severe COVID-19.

Original languageEnglish
Article number130
Number of pages4
JournalRespiratory Research
Volume24
DOIs
Publication statusPublished - 11-May-2023

Keywords

  • ACE2
  • Cigarette smoking
  • COVID-19
  • SARS-CoV-2

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