PT - JOURNAL ARTICLE AU - Abby C. Lee AU - Jaideep Chakladar AU - Wei Tse Li AU - Chengyu Chen AU - Eric Y. Chang AU - Jessica Wang-Rodriguez AU - Weg M. Ongkeko TI - Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation AID - 10.1101/2020.07.13.198630 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.07.13.198630 4099 - http://biorxiv.org/content/early/2020/07/13/2020.07.13.198630.short 4100 - http://biorxiv.org/content/early/2020/07/13/2020.07.13.198630.full AB - 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 StatementThe authors have declared no competing interest.PGpropylene glycolVGvegetable glycerinLUSClung squamous cell carcinomaMSigDBMolecular Signatures DatabaseTNFtumor necrosis factorlimmaLinear Models for Microarray AnalysisTregRegulatory T cellsPBMCsPeripheral Blood Mononuclear CellsTCGAThe Cancer Genome Atlas