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      Distribution of ACE2, CD147, CD26 and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors

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          Abstract

          Background

          Morbidity and mortality from COVID‐19 caused by novel coronavirus SARS‐CoV‐2 is accelerating worldwide and novel clinical presentations of COVID‐19 are often reported. The range of human cells and tissues targeted by SARS‐CoV‐2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS‐CoV‐2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID‐19.

          Methods

          We performed RNA sequencing and explored available RNA‐Seq databases to study gene expression and co‐expression of ACE2, CD147 ( BSG), CD26 ( DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4 + and CD8 + T cells, B cells and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID‐19 risk factor status.

          Results

          ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 ( BSG), cyclophilins ( PPIA and PPIB), CD26 ( DPP4) and related molecules were expressed in both, epithelium and in immune cells. We also observed a distinct age‐related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2‐ and CD147‐related genes in the bronchial biopsy, BAL or blood. Additionally, CD147‐related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of ACE2‐ and CD147‐related genes in the lesional skin of patients with atopic dermatitis.

          Conclusions

          Our data suggest different receptor repertoire potentially involved in the SARS‐CoV‐2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related with age, gender, obesity and smoking, as well as with the disease status might contribute to COVID‐19 morbidity and severity patterns.

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          Author and article information

          Contributors
          milena.sokolowska@siaf.uzh.ch
          Journal
          Allergy
          Allergy
          10.1111/(ISSN)1398-9995
          ALL
          Allergy
          John Wiley and Sons Inc. (Hoboken )
          0105-4538
          1398-9995
          04 June 2020
          : 10.1111/all.14429
          Affiliations
          [ 1 ] Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
          [ 2 ] Christine Kühne – Center for Research and Education (CK‐CARE) Davos Switzerland
          [ 3 ] Department of Regenerative Medicine and Immune Regulation Medical University of Bialystok Bialystok Poland
          [ 4 ] Department of Allergology Zhongnan Hospital of Wuhan University Wuhan China
          [ 5 ] Functional Genomic Centre Zurich ETH Zurich/University of Zurich Zurich Switzerland
          [ 6 ] Otorhinolaryngology Hospital The First Affiliated Hospital Sun Yat‐sen University Guangzhou China
          [ 7 ] Division of Clinical Chemistry and Biochemistry University Children`s Hospital Zurich, Zurich, Switzerland; Children`s Research Center, University Children`s Hospital Zurich Zurich Switzerland
          [ 8 ] Department of Otolaryngology, Head and Neck Surgery Beijing TongRen Hospital, Capital Medical University and the Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology Beijing China
          [ 9 ] Department of Cancer Immunology Institute for Cancer Research Oslo University Hospital Oslo Norway
          [ 10 ] Department of Allergy and Clinical Immunology National Research Institute for Child Health and Development Tokyo Japan
          [ 11 ] Chair and Institute of Environmental Medicine UNIKA‐T Technical University of Munich and Helmholtz Zentrum Munchen Augsburg Germany
          [ 12 ] Institute of Computational Biology (ICB) Helmholtz Zentrum Munchen Munich Germany
          [ 13 ] Institute of Experimental Medicine (IEM) Czech Academy of Sciences Prague Czech Republic
          [ 14 ] Sean N Parker Centre for Allergy and Asthma Research at Stanford University Department of Medicine, Stanford University School of Medicine Stanford USA
          [ 15 ] Department of Medicine and School of Microbiology APC Microbiome Ireland National University of Ireland Cork Ireland
          Author notes
          [*] [* ] Corresponding author

          Milena Sokolowska MD, PhD, Head Immune Metabolism, Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Herman‐Burchard‐Strasse 9, CH‐7265 Davos‐Wolfgang, Tel: +41 (0) 81 410 08 44

          Email:  milena.sokolowska@ 123456siaf.uzh.ch

          [†]

          equal contribution

          Article
          ALL14429
          10.1111/all.14429
          7300910
          32496587
          e2ec09bd-6799-4185-9c50-9c91e431860c
          This article is protected by copyright. All rights reserved.

          This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

          History
          Page count
          Figures: 0, Tables: 0, Pages: 37, Words: 738
          Categories
          Original Article: Basic and Translational Allergy Immunology
          Original Article: Basic and Translational Allergy Immunology
          Custom metadata
          2.0
          accepted-manuscript
          Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:18.06.2020

          Immunology
          asthma,copd,covid‐19,covid‐19 children,hypertension,obesity,sars receptor
          Immunology
          asthma, copd, covid‐19, covid‐19 children, hypertension, obesity, sars receptor

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