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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.
Viruses. 2021 Jun 05; 13(6)V

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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Authors+Show Affiliations

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.

MeSH

AsthmaCOVID-19Coronavirus 229E, HumanCoronavirus InfectionsEpithelial CellsFemaleGene ExpressionGene Expression ProfilingHost Microbial InteractionsHumansInfluenza, HumanMaleMiddle East Respiratory Syndrome CoronavirusOrthomyxoviridaeSARS-CoV-2Severity of Illness IndexSex Characteristics

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34198852

Citation

Coden, Mackenzie E., et al. "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." Viruses, vol. 13, no. 6, 2021.
Coden ME, Loffredo LF, Abdala-Valencia H, et al. 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. Viruses. 2021;13(6).
Coden, M. E., Loffredo, L. F., Abdala-Valencia, H., & Berdnikovs, S. (2021). 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. Viruses, 13(6). https://doi.org/10.3390/v13061081
Coden ME, et al. 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. Viruses. 2021 Jun 5;13(6) PubMed PMID: 34198852.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Coden,Mackenzie E, AU - Loffredo,Lucas F, AU - Abdala-Valencia,Hiam, AU - Berdnikovs,Sergejs, Y1 - 2021/06/05/ PY - 2021/5/5/received PY - 2021/5/24/revised PY - 2021/5/26/accepted PY - 2021/7/2/entrez PY - 2021/7/3/pubmed PY - 2021/7/15/medline KW - COVID-19 KW - HCoV-229E KW - MERS KW - SARS KW - allergy KW - asthma KW - epithelium KW - gene expression KW - inflammation KW - influenza KW - sexual dimorphism KW - virus JF - Viruses JO - Viruses VL - 13 IS - 6 N2 - 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. SN - 1999-4915 UR - https://www.unboundmedicine.com/medline/citation/34198852/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_ DB - PRIME DP - Unbound Medicine ER -