In a recent study published in bioRxiv* Preprint server Researchers at the University of California, Riverside investigated the effects of e-cigarette (EC) use as a risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Stady: Does vaping increase the risk of SARS-CoV-2 infection? Ironically, yes and no. Image Credit: DedMityay / Shutterstock
Electroconductors, nicotine-delivery compounds that infuse e-liquids, contain nicotine, propylene glycol (PG), vegetable glycerin (VG), and flavoring chemicals. They are sometimes promoted as less dangerous than tobacco cigarettes; However, it is not harmless. There is increasing evidence that EC aerosol increases angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 virus receptor, increasing its binding to host cells, a critical step for establishing infection in humans. However, there is a lack of studies looking at the relationship between ECs and coronavirus disease 2019 (COVID-19) in humans; Moreover, the available data are contradictory.
In this study, researchers used EpiAirway™ tissues, three-dimensional (3D) organoid cultures of human bronchial epithelium containing ciliated, basal, and mucosal cells to elucidate the effect of vaping and identify specific chemicals in EC fluids on COVID-19.
A previous study showed that EC aerosols increased ACE2 activity and soluble ACE2 levels in bronchoalveolar lavage fluid (BLF) users of EC users. In the current study, the team also measured ACE2 and transmembrane protease levels, serine protease 2 (TMPRSS2) activity in EpiAirway™ tissues, and the magnitude of SARS-CoV-2 pseudopod infection.
For the 3D EpiAirway™ tissue infection experiments, the team used 0.3 multiple-infection (MOI) of SARS-CoV-2 pseudo-particles. The study protocol simulated acute EC exposure to EpiAirway™ tissue over three days, with 50 puffs per day, the range typically received by an EC user. The team made sure the tissue was returned to the incubator between each exposure day. After the last exposure and before the analyses, they again allowed the tissues to recover in the incubator for 24 h.
The Cultex® system produced original EC aerosols, including chemicals in the e-liquid as well as reaction products and minerals formed by heating e-liquids in a cloud chamber. The combination of air-liquid interfaces (ALI) exposure systems in tandem with 3D EpiAirway™ models has provided an innovative setup that is superior to human trials for understanding how aerosols and viral infections affect the human respiratory system.
The authors note that aerosols containing PG, VG, and nicotine enhanced infection of EpiAirway™ tissues by SARS-CoV-2 pseudo-particles in a dose-dependent manner. Notably, benzoic acid provided significant protection against the infection-promoting effects of PG/VG and nicotine for at least 48 h after AL exposure had ceased, likely because pH levels returned to normal during this time after vaping. However, BLU™ EC aerosol, which lacks benzoic acid, increased pseudo-particle infection, indicating that this infection varies with EC brand and e-liquid content. This is why even a low-power JUUL™ battery, combined with a third-party pod, causes PG/VG or nicotine-enhanced infection.
The authors observed a significant correlation between TMPRSS2 activity and the pH of the effluent e-liquid. Accordingly, the results of the study indicated that a lower pH of the e-liquid volatilized reduces infection levels in EpiAirway™ tissues. Therefore, the most likely explanation is that benzoic acid lowers the pH at ALI to a level that reduces TMPRSS2 activity, which in turn reduces infection. Also, a low-pH aerosol (eg, Joll™ aerosol) is likely to reduce exposure to encoded receptor-binding domains (RBDs) of the SARS-CoV-2 spike (S) protein and thus reduce its ability to bind to ACE2.
Future studies should determine whether benzoic acid and its derivatives interact with the proteases involved in the SARS-CoV-2 repeat to evaluate its effects in the later stages of SARS-CoV-2 disease pathogenesis. Furthermore, the authors noted varying infection-promoting effects due to differences in exposure protocols. This result indicated that user topography, which influences exposure to nicotine, could influence health outcomes for EC users.
The current study demonstrated a complex relationship between vaping and SARS-CoV-2 infection, which was highly dependent on the components of the e-liquid used to create the aerosol. The study data will provide EC users with options to reduce the risk of contracting COVID-19. For example, an acid-containing product may help reduce a viral infection. However, the authors caution that inhaling benzoic or other acids into ECs may have adverse health consequences as well. However, the study data could help design future studies to examine the effects of e-cigarette products on SARS-CoV-2 infection.
bioRxiv It publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behaviour, or be treated as established information.