Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation

Int J Mol Sci. 2020 Jul 31;21(15):5513. doi: 10.3390/ijms21155513.


The COVID-19 pandemic caused by the SARS-CoV-2 virus, overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined three independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cigs led to upregulation of pro-inflammatory cytokines and inflammasome-related genes. Specifically, chemokines including CCL20 and CXCL8 are upregulated in smokers, and CCL5 and CCR1 are upregulated in flavor/nicotine-containing e-cig users. We also found genes implicated in inflammasomes, such as CXCL1, CXCL2, NOD2, and ASC, to be upregulated in smokers and these e-cig users. Vaping flavor and nicotine-less e-cigs, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping may critically exacerbate COVID-19-related inflammation or increase susceptibility to COVID-19.

Keywords: ACE2; COVID-19; SARS-CoV-2; cytokines; electronic cigarettes; immune response; inflammation; tobacco; vaping.

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / isolation & purification
  • Bronchi / cytology
  • COVID-19
  • Chemokine CCL20 / genetics
  • Chemokine CCL20 / metabolism
  • Coronavirus Infections / pathology
  • Coronavirus Infections / virology
  • Electronic Nicotine Delivery Systems*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Humans
  • Immune System / metabolism*
  • Interleukin-1beta / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Middle Aged
  • Nod2 Signaling Adaptor Protein / genetics
  • Nod2 Signaling Adaptor Protein / metabolism
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Tobacco Smoking*
  • Up-Regulation
  • Young Adult


  • Chemokine CCL20
  • Interleukin-1beta
  • Interleukin-8
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2