Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium
Abstract
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 bothACE2andTMPRSS2, that vary in frequency across world populations. Importantly, we findTMPRSS2is 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 upregulatesACE2expression. Finally, we define airway responses to coronavirus infections in children, finding that these infections upregulateIL6while 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.
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