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Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation

Abby C. Lee, Jaideep Chakladar, Wei Tse Li, Chengyu Chen, Eric Y. Chang, Jessica Wang-Rodriguez, Weg M. Ongkeko
doi: https://doi.org/10.1101/2020.07.13.198630
Abby C. Lee
1Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (A.L.); (J.C.); (W.T.L.); (C.C.); (W.M.O)
2Research Service, VA San Diego Healthcare System San Diego, La Jolla, CA 92161, USA; (A.L.); (J.C.); (W.T.L.); (W.M.O)
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  • For correspondence: acl008@ucsd.edu jchaklad@ucsd.edu wtl008@ucsd.edu chc401@ucsd.edu rongkeko@health.ucsd.edu acl008@ucsd.edu jchaklad@ucsd.edu wtl008@ucsd.edu rongkeko@health.ucsd.edu
Jaideep Chakladar
1Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (A.L.); (J.C.); (W.T.L.); (C.C.); (W.M.O)
2Research Service, VA San Diego Healthcare System San Diego, La Jolla, CA 92161, USA; (A.L.); (J.C.); (W.T.L.); (W.M.O)
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  • For correspondence: acl008@ucsd.edu jchaklad@ucsd.edu wtl008@ucsd.edu chc401@ucsd.edu rongkeko@health.ucsd.edu acl008@ucsd.edu jchaklad@ucsd.edu wtl008@ucsd.edu rongkeko@health.ucsd.edu
Wei Tse Li
1Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (A.L.); (J.C.); (W.T.L.); (C.C.); (W.M.O)
2Research Service, VA San Diego Healthcare System San Diego, La Jolla, CA 92161, USA; (A.L.); (J.C.); (W.T.L.); (W.M.O)
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  • For correspondence: acl008@ucsd.edu jchaklad@ucsd.edu wtl008@ucsd.edu chc401@ucsd.edu rongkeko@health.ucsd.edu acl008@ucsd.edu jchaklad@ucsd.edu wtl008@ucsd.edu rongkeko@health.ucsd.edu
Chengyu Chen
1Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (A.L.); (J.C.); (W.T.L.); (C.C.); (W.M.O)
2Research Service, VA San Diego Healthcare System San Diego, La Jolla, CA 92161, USA; (A.L.); (J.C.); (W.T.L.); (W.M.O)
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  • For correspondence: acl008@ucsd.edu jchaklad@ucsd.edu wtl008@ucsd.edu chc401@ucsd.edu rongkeko@health.ucsd.edu acl008@ucsd.edu jchaklad@ucsd.edu wtl008@ucsd.edu rongkeko@health.ucsd.edu
Eric Y. Chang
3Department of Radiology, Radiology Service, VA San Diego Healthcare System San Diego, University of California San Diego, La Jolla, CA 92093, USA;
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  • For correspondence: Eric.Chang2@va.gov
Jessica Wang-Rodriguez
4Department of Pathology, Pathology Service, VA San Diego Healthcare System San Diego, University of California San Diego, La Jolla, CA 92093, USA;
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  • For correspondence: Jessica.Wang-Rodriguez@va.gov
Weg M. Ongkeko
1Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (A.L.); (J.C.); (W.T.L.); (C.C.); (W.M.O)
2Research Service, VA San Diego Healthcare System San Diego, La Jolla, CA 92161, USA; (A.L.); (J.C.); (W.T.L.); (W.M.O)
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Abstract

COVID-19, caused by the virus SARS-CoV-2, has infected millions worldwide. This pandemic overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping, with over 1 billion smokers and vapers worldwide. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined 3 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-cig led to upregulations of pro-inflammatory cytokine production and expression of genes related to inflammasomes. Vaping flavor-less and nicotine-less e-cig, 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, specifically use of flavored or nicotine-containing e-cigs, may critically exacerbate COVID-19-related inflammation or increase susceptibility to the disease. Further scientific and public health investigations should be undertaken to address these concerning links between COVID-19 and e-cig/smoking.

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations

    PG
    propylene glycol
    VG
    vegetable glycerin
    LUSC
    lung squamous cell carcinoma
    MSigDB
    Molecular Signatures Database
    TNF
    tumor necrosis factor
    limma
    Linear Models for Microarray Analysis
    Treg
    Regulatory T cells
    PBMCs
    Peripheral Blood Mononuclear Cells
    TCGA
    The Cancer Genome Atlas
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    Posted July 13, 2020.
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    Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation
    Abby C. Lee, Jaideep Chakladar, Wei Tse Li, Chengyu Chen, Eric Y. Chang, Jessica Wang-Rodriguez, Weg M. Ongkeko
    bioRxiv 2020.07.13.198630; doi: https://doi.org/10.1101/2020.07.13.198630
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    Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation
    Abby C. Lee, Jaideep Chakladar, Wei Tse Li, Chengyu Chen, Eric Y. Chang, Jessica Wang-Rodriguez, Weg M. Ongkeko
    bioRxiv 2020.07.13.198630; doi: https://doi.org/10.1101/2020.07.13.198630

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