Comparative study of sars-cov-2, sars-cov-1, mers-cov, hcov-229e and influenza host gene expression in asthma: Importance of sex, disease severity, and epithelial heterogeneity

Mackenzie E. Coden, Lucas F. Loffredo, Hiam Abdala-Valencia, Sergejs Berdnikovs*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 the expression of SARS-CoV-2-related 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 SARS-CoV-2-related gene expression were specific to the 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 wascorrelated with loss of club and ciliated cells in Th2 high asthma. Meanwhile, the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) was associated with increased goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype, and changes in epithelial heterogeneity as potential factors underlying asthmatic susceptibility, or lack thereof, to SARS-CoV-2.

Original languageEnglish (US)
Article number1081
JournalViruses
Volume13
Issue number6
DOIs
StatePublished - Jun 2021

Keywords

  • Allergy
  • Asthma
  • COVID-19
  • Epithelium
  • Gene expression
  • HCoV-229E
  • Inflammation
  • Influenza
  • MERS
  • SARS
  • Sexual dimorphism
  • Virus

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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