A large body of evidence shows the harmful effects of cigarette smoke to oral and systemic health. More recently, a link between smoking and susceptibility to coronavirus disease 2019 (COVID-19) was proposed. COVID-19 is due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses the receptor ACE2 and the protease TMPRSS2 for entry into host cells, thereby infecting cells of the respiratory tract and the oral cavity. Here, we examined the effects of cigarette smoke on the expression of SARS-CoV-2 receptors and infection in human gingival epithelial cells (GECs). We found that cigarette smoke condensates (CSC) upregulated ACE2 and TMPRSS2 expression in GECs, and that CSC activated aryl hydrocarbon receptor (AhR) signaling in the oral cells. ACE2 was known to mediate SARS-CoV-2 internalization, and we demonstrate that CSC treatment potentiated the internalization of SARS-CoV-2 pseudovirus in GECs in an AhR-dependent manner. AhR depletion using small interference RNA decreased SARS-CoV-2 pseudovirus internalization in CSC-treated GECs compared with control GECs. Our study reveals that cigarette smoke upregulates SARS-CoV-2 receptor expression and infection in oral cells. Understanding the mechanisms involved in SARS-CoV-2 infection in cells of the oral cavity may suggest therapeutic interventions for preventing viral infection and transmission.

Conventional cigarette smoke harms nearly every organ of the body and is the leading cause of death in the United States and in the world. Decades of research have associated conventional cigarette smoke with several diseases and death. Heavily marketed, electronic nicotine delivery systems such as electronic cigarettes (e-cigarettes) are available in a variety of flavors and high nicotine concentrations. In 2019, a severe lung disease outbreak linked to e-cigarette use led to several deaths, which was called electronic-cigarette or vaping product use-associated lung injury (EVALI). Even though the trend of e-cigarette use among teens continues to increase, information on the effects of e-cigarette smoke on oral and overall health are still scarce. This review discusses the possible health effects due to unregulated e-cigarette use, as well as the health effects of second-hand smoke and third-hand smoke on non-smokers.