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

Radzikowska U. 1,2,3*, Ding M. 1,2,4*, Tan G. 1,5, Zhakparov D. 1, Peng Y. 1,2,6, Wawrzyniak P. 1,2,7, Wang M. 1,2,8, Li S. 1,9, Morita H. 1,10, Altunbulakli C. 1,2, Reiger M. 11, Neumann AU. 11,12,13, Lunjani N. 1,2, Traidl-Hoffmann C. 2,11, Nadeau K. 14, O’Mahony L. 1,15, Akdis CA. 1,2, Sokolowska M. 1,2
*equal contribution

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

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.

Urszula Radzikowska MSc

Swiss Institute of Allergy and Asthma Research

Appearances