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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.
Coden, Mackenzie E; Loffredo, Lucas F; Abdala-Valencia, Hiam; Berdnikovs, Sergejs.
  • Coden ME; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • Loffredo LF; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • Abdala-Valencia H; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • Berdnikovs S; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Viruses ; 13(6)2021 06 05.
Article in English | MEDLINE | ID: covidwho-1259626
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Asthma / Severity of Illness Index / Gene Expression / Coronavirus Infections / Epithelial Cells / Influenza, Human / Host Microbial Interactions / COVID-19 Type of study: Prognostic study Limits: Female / Humans / Male Language: English Year: 2021 Document Type: Article Affiliation country: V13061081

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Asthma / Severity of Illness Index / Gene Expression / Coronavirus Infections / Epithelial Cells / Influenza, Human / Host Microbial Interactions / COVID-19 Type of study: Prognostic study Limits: Female / Humans / Male Language: English Year: 2021 Document Type: Article Affiliation country: V13061081