Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia

In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need. [Display omitted] We use reconstituted human airway epithelia to characterize SARS-CoV-2 infection kineticsSARS-CoV-2 induces characteristic remodeling of the respiratory epithelium cellular ultrastructureSARS-CoV-2 induces differential early immune responses in nasal and bronchial HAEWe evaluate the antiviral activity of remdesivir and remdesivir-diltiazem in both Vero E6 and HAE models Pizzorno et al. report the characterization of SARS-CoV-2 infection, tissue-level remodeling of cellular ultrastructure, and transcriptional immune signatures using a model of reconstituted human airway epithelia. This model was advantageously used to evaluate the antiviral activity of remdesivir or a combination of remdesivir-diltiazem against SARS-CoV-2.