Preprint Brief Report Version 1 Preserved in Portico This version is not peer-reviewed

Comparative Study of Epithelial Entry Gene Expression of SARS-Cov-2 and Other Human Viral Species in Asthma: Differences by Sex, Airway Location Aand Disease Endotype

Version 1 : Received: 12 January 2021 / Approved: 14 January 2021 / Online: 14 January 2021 (12:37:08 CET)

How to cite: Coden, M.; Loffredo, L.; Abdala-Valencia, H.; Berdnikovs, S. Comparative Study of Epithelial Entry Gene Expression of SARS-Cov-2 and Other Human Viral Species in Asthma: Differences by Sex, Airway Location Aand Disease Endotype. Preprints 2021, 2021010266 (doi: 10.20944/preprints202101.0266.v1). Coden, M.; Loffredo, L.; Abdala-Valencia, H.; Berdnikovs, S. Comparative Study of Epithelial Entry Gene Expression of SARS-Cov-2 and Other Human Viral Species in Asthma: Differences by Sex, Airway Location Aand Disease Endotype. Preprints 2021, 2021010266 (doi: 10.20944/preprints202101.0266.v1).

Abstract

Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate and severe asthmatics, we characterized the changes in expression of human coronavirus and influenza viral entry genes relative to sex, airway location and disease endotype. We found sexual dimorphism in expression of COVID-19 genes ACE2, TMPRSS2, TMPRSS4, and SLC6A19. ACE2 receptor downregulation occurred specifically in females in Th2 high asthma, while proteases broadly assisting coronavirus and influenza viral entry, TMPRSS2 and TMPRSS4, were highly upregulated in both sexes. Overall, changes in COVID-19 gene expression were specific to Th2 high molecular endotype of asthma, and different by asthma severity and airway location. The downregulation of ACE2 (COVID-19, SARS) and ANPEP (HCoV-229E) viral receptors correlated with loss of club and ciliated cells in Th2 high asthma, while the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) associated with an increase in goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype and changes in epithelial heterogeneity as factors underlying asthmatic susceptibility, or lack thereof, to COVID-19.

Subject Areas

COVID-19; SARS; HCoV-229E; MERS; influenza; virus; epithelium; asthma; allergy; inflammation; sexual dimorphism; gene expression

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