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Determinants of SARS-CoV-2 receptor gene expression in upper and lower airways

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Title:Determinants of SARS-CoV-2 receptor gene expression in upper and lower airways
Creators Name:Aliee, H. and Massip, F. and Qi, C. and Stella de Biase, M. and van Nijnatten, J.L. and Kersten, E.T.G. and Kermani, N.Z. and Khuder, B. and Vonk, J.M. and Vermeulen, R.C.H. and Neighbors, M. and Tew, G.W. and Grimbaldeston, M. and Ten Hacken, N.H.T. and Hu, S. and Guo, Y. and Zhang, X. and Sun, K. and Hiemstra, P.S. and Ponder, B.A. and Makela, M.J. and Malmstrom, K. and Rintoul, R.C. and Reyfman, P.A. and Theis, F.J. and Brandsma, C.A. and Adcock, I. and Timens, W. and Xu, C.J. and van den Berge, M. and Schwarz, R.F. and Koppelman, G.H. and Nawijn, M.C. and Faiz, A.
Abstract:The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. One week after initial symptoms develop, a subset of patients progresses to severe disease, with high mortality and limited treatment options. To design novel interventions aimed at preventing spread of the virus and reducing progression to severe disease, detailed knowledge of the cell types and regulating factors driving cellular entry is urgently needed. Here we assess the expression patterns in genes required for COVID-19 entry into cells and replication, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). Matched samples from the upper and lower airways show a clear increased expression of these genes in the nose compared to the bronchi and parenchyma. Cellular deconvolution indicates a clear association of these genes with the proportion of secretory epithelial cells. Smoking status was found to increase the majority of COVID-19 related genes including ACE2 and TMPRSS2 but only in the lower airways, which was associated with a significant increase in the predicted proportion of goblet cells in bronchial samples of current smokers. Both acute and second hand smoke were found to increase ACE2 expression in the bronchus. Inhaled corticosteroids decrease ACE2 expression in the lower airways. No significant effect of genetics on ACE2 expression was observed, but a strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified in the bronchus.
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.08.31.20169946
Date:2 September 2020
Official Publication:https://doi.org/10.1101/2020.08.31.20169946

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