Airway Basal Stem Cells in COVID-19 Exhibit a Proinflammatory Signature and Impaired Mucocililary Differentiation.

Airway basal stem cells (BSCs) play a critical role in epithelial regeneration. Whether COVID-19 (CoV19) affects the function of BSCs is unknown. Here, we derived BSC lines from CoV19 patients using tracheal aspirates (TA) to circumvent biosafety concerns of live cell derivation. We show that BSCs derived from TA of control patients are bona fide bronchial BSCs. TA BSCs from CoV19 patients tested negative for SARS-CoV-2 RNA; however, these so-termed CoV19-exposed BSCs in vitro resemble a predominant BSC subpopulation uniquely present in CoV19 patients, manifested by a proinflammatory gene signature and STAT3 hyperactivation. Furthermore, the sustained, STAT3 hyperactivation drives goblet cell differentiation of CoV19-exposed BSCs in air-liquid interface. Lastly, these phenotypes of CoV19-exposed BSCs can be induced in control BSCs by cytokine cocktail pretreatment. Taken together, acute inflammation in CoV19 exerts a long-term impact on mucociliary differentiation of BSCs. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).