%0 Journal Article %J bioRxiv %D 2020 %T Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium. %A Sajuthi, Satria P %A DeFord, Peter %A Jackson, Nathan D %A Montgomery, Michael T %A Everman, Jamie L %A Rios, Cydney L %A Pruesse, Elmar %A Nolin, James D %A Plender, Elizabeth G %A Wechsler, Michael E %A Mak, Angel Cy %A Eng, Celeste %A Salazar, Sandra %A Medina, Vivian %A Wohlford, Eric M %A Huntsman, Scott %A Nickerson, Deborah A %A Germer, Soren %A Zody, Michael C %A Abecasis, Gonçalo %A Kang, Hyun Min %A Rice, Kenneth M %A Kumar, Rajesh %A Oh, Sam %A Rodriguez-Santana, Jose %A Burchard, Esteban G %A Seibold, Max A %X

Coronavirus disease 2019 (COVID-19) outcomes vary from asymptomatic infection to death. This disparity may reflect different airway levels of the SARS-CoV-2 receptor, ACE2, and the spike protein activator, TMPRSS2. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci (eQTL) for both and , that vary in frequency across world populations. Importantly, we find is part of a mucus secretory network, highly upregulated by T2 inflammation through the action of interleukin-13, and that interferon response to respiratory viruses highly upregulates expression. Finally, we define airway responses to coronavirus infections in children, finding that these infections upregulate while also stimulating a more pronounced cytotoxic immune response relative to other respiratory viruses. Our results reveal mechanisms likely influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes.

%B bioRxiv %8 2020 Apr 10 %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/32511326?dopt=Abstract %R 10.1101/2020.04.09.034454