RT Journal Article SR Electronic T1 Does Vaping Increase the Likelihood of SARS-CoV-2 Infection? Paradoxically Yes and No JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.09.09.507373 DO 10.1101/2022.09.09.507373 A1 Rattapol Phandthong A1 Man Wong A1 Ann Song A1 Teresa Martinez A1 Prue Talbot YR 2022 UL http://biorxiv.org/content/early/2022/09/13/2022.09.09.507373.abstract AB Data on the relationship between electronic cigarettes (ECs) and SARS-CoV-2 infection are limited and contradictory. Evidence indicates that EC aerosols or nicotine increase ACE2, SARS-CoV-2 virus receptors, which increase virus binding and susceptibility. Our objectives were to determine if EC aerosols increased SARS-CoV-2 infection of human bronchial epithelial cells and to identify the causative chemical(s). A 3D organotypic model (EpiAirway™) in conjunction with air liquid interface (ALI) exposure was used to test the effects of aerosols produced from JUUL™ “Virginia Tobacco” and BLU™ ECs, or individual chemicals (nicotine, propylene glycol, vegetable glycerin (PG/VG), and benzoic acid) on infection using SARS-CoV-2 pseudoparticles. Exposure of EpiAirway™ to JUUL™ aerosols increased ACE2, while BLU™ and lab-made EC aerosols containing nicotine increased ACE2 levels and TMPRSS2 activity, a spike protease that enables viral-cell fusion. Pseudoparticle infection of EpiAirway™ increased with aerosols produced from PG/VG, PG/VG plus nicotine, or BLU™ ECs. JUUL™ EC aerosols did not increase infection above controls. The baseline level of infection in JUUL™ treated aerosol groups was attributed to benzoic acid, which mitigated the enhanced infection caused by PG/VG or nicotine. The benzoic acid protection from enhanced infection continued at least 48 hours after exposure. TMPRSS2 activity was significantly correlated with e-liquid pH, which in turn was significantly correlated with infection, with lower pH blocking PG/VG and nicotine-induced-enhanced infection. While ACE2 levels increased in EpiAirway™ tissues exposed to EC aerosols, infection depended on the ingredients of the e-liquids. PG/VG and nicotine enhanced infection, an effect that was mitigated by benzoic acid.Competing Interest StatementThe authors have declared no competing interest.