Fluticasone propionate suppresses the SARS-CoV-2 induced increase in respiratory epithelial permeability in vitro

BACKGROUND: Disruption of the nasal epithelial barrier is believed to play a role in Coronavirus Disease-2019 (COVID-19) outcomes. Fluticasone propionate has been shown to restore the nasal epithelial barrier in allergic rhinitis to the level of healthy controls. The therapeutic potential of nasal steroid sprays in COVID-19 has recently been reported. However, further insight into the mode of action is warranted. OBJECTIVES: To explore the in vitro mechanisms of the preventive potential of fluticasone propionate in SARS-CoV-2 infection. METHODS: Human air liquid interface cultures of Calu-3 cells and primary nasal epithelial cells isolated from healthy donors were used to investigate the preventive effect of fluticasone propionate on SARS-CoV-2 induced barrier disruption, virus replication and ACE2 expression. RESULTS: 48 hours pre-treatment with fluticasone propionate prevented the SARS-CoV-2 induced increase in fluorescein isothiocyanate-dextran 4 kDa permeability and reduced infection with SARS-CoV-2. Pre-treatment with fluticasone propionate also decreased ACE2 expression in SARS-CoV-2 infected Calu-3 cells. Conclusion: Fluticasone propionate pre-treatment prevented SARS-CoV-2 increased epithelial permeability, reduced ACE2 expression and SARS-CoV-2 infection, underscoring the therapeutic potential of fluticasone propionate in the context of COVID-19.