E-cigarette vape and lung ACE2 expression: Implications for coronavirus vulnerability

Environ Toxicol Pharmacol. 2021 Aug;86:103656. doi: 10.1016/j.etap.2021.103656. Epub 2021 Apr 7.


Evidence in humans suggests a correlation between nicotine smoking and severe respiratory symptoms with COVID-19 infection. In lung tissue, angiotensin-converting enzyme 2 (ACE2) appears to mechanistically underlie viral entry. Here, we investigated whether e-cigarette vapor inhalation alters ACE2 and nicotinic acetylcholine receptor (nAChR) expression in male and female mice. In male lung, nicotine vapor inhalation induced a significant increase in ACE2 mRNA and protein, but surprisingly, these differences were not found in females. Further, both vehicle and nicotine vapor inhalation downregulated α5 nAChR subunits in both sexes, while differences were not found in α7 nAChR subunit expression. Finally, blood ACE2 levels did not differ with exposure, indicating that blood sampling is not a sufficient indicator of lung ACE2 changes. Together, these data indicate a direct link between e-cigarette vaping and increased ACE2 expression in male lung tissue, which thereby reveals an underlying mechanism of increased vulnerability to coronavirus infection in individuals vaping nicotine.

Keywords: ACE2; COVID-19; E-cigarette; Individual differences; Lung; Nicotine.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / biosynthesis*
  • Angiotensin-Converting Enzyme 2 / blood
  • Angiotensin-Converting Enzyme 2 / genetics
  • Animals
  • COVID-19 / epidemiology*
  • DNA, Complementary / biosynthesis
  • Electronic Nicotine Delivery Systems*
  • Female
  • Lung / cytology
  • Lung / enzymology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nicotine / administration & dosage
  • Nicotine / pharmacology
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology
  • Receptors, Nicotinic / biosynthesis
  • Sex Characteristics
  • Vaping / adverse effects*
  • alpha7 Nicotinic Acetylcholine Receptor / metabolism


  • DNA, Complementary
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Nicotine
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2