1. Determinants of expression of SARS-CoV-2 entry-related genes in upper and lower airways
- Author
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K Malmström, A. Faiz, Maria Stella de Biase, Corry-Anke Brandsma, Michele A. Grimbaldeston, Gaik W. Tew, Basil Khuder, Cheng-Jian Xu, G. H. Koppelman, Pieter S. Hiemstra, Cancan Qi, Sile Hu, Roland F. Schwarz, Hananeh Aliee, Paul A. Reyfman, Florian Massip, Robert C. Rintoul, N. H. Hacken, Fabian J. Theis, Ian M. Adcock, Xiaoyu Zhang, Nazanin Zounemat Kermani, Bruce A.J. Ponder, Mika J. Mäkelä, Martijn C. Nawijn, Elin T G Kersten, Jos van Nijnatten, Judith M. Vonk, Roel Vermeulen, Kai Sun, Yike Guo, W. Timens, Margaret Neighbors, Maarten van den Berge, Groningen Research Institute for Asthma and COPD (GRIAC), Guided Treatment in Optimal Selected Cancer Patients (GUTS), HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, Commission of the European Communities, Medical Research Council (MRC), and Engineering & Physical Science Research Council (EPSRC)
- Subjects
0303 health sciences ,2019-20 coronavirus outbreak ,Science & Technology ,Letter ,Coronavirus disease 2019 (COVID-19) ,Allergy ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,INER-Ciencias Mexican Lung Program ,Virology ,Cambridge Lung Cancer Early Detection Programme ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,1107 Immunology ,3121 General medicine, internal medicine and other clinical medicine ,Immunology and Allergy ,Medicine ,U-BIOPRED study group ,Letters ,business ,Gene ,Life Sciences & Biomedicine ,030304 developmental biology - 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.
- Published
- 2022