22 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

Ding Mei1/2/4*, Radzikowska Urszula1/2/3*, Tan Ge1/5, Zhakparov Damir1, Peng Yaqi1/2/6, Wawrzyniak Paulina1/2/7, Wang Ming1/2/8, Li Shuo1/9, Morita Hideaki1/10, Altunbulakli Can1/2, Reiger Matthias11, Neumann Avidan11/12/13, Lunjani Nonhlanhla1/2, Traidl-Hoffmann Claudia2/11, Nadeau Kari14, O’Mahony Liam1/15, Akdis Cezmi A.1/2, Sokolowska Milena1,2

*equal contribution

  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 München, Augsburg, Germany
  12. Institute of Computational Biology (ICB), Helmholtz Zentrum München, 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

Background: COVID-19 caused by SARS-CoV-2 has become pandemic worldwide. The human cells and tissues targeted by SARS-CoV-2, its receptors and interactive factors are largely unknown. The aim of our study was to analyze the expression of proven and potential SARS-CoV-2 receptors and associated molecules in human immune cells and epithelial tissues from healthy controls of different ages and from patients with COVID-19 risk factors and comorbidities.

Method: We performed RNA-sequencing and analyzed available RNA-seq databases to investigate gene expression of ACE2, CD147 (BSG), CD26 (DPP4) and related molecules in differentiated human bronchial epithelial cells (HBECs), bronchial biopsies, skin tissues, bronchoalveolar lavage (BAL) 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 also explored the expression of these genes in variable clinical features including age, asthma, chronic obstructive pulmonary disease (COPD), hypertension, smoking, obesity and gender.

Results: ACE2 was coexpressed with TMPRSS2 in lung epithelium and skin tissues while CD147-related genes and DPP4 (CD26) were expressed broadly in epithelium and immune cells. We also noted distinct gene expression patterns of several CD147-, CD26-related genes in PBMCs and naïve CD4+ T cells between 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. We also observed a positive correlation between CD147-related genes and BMI or age. Lesional skin biopsy in atopic dermatitis showed higher expression of several CD147-related genes.

Conclusion:Our data suggest SARS-CoV-2 could potentially interact with different receptors in immune cells, lung and skin epithelium. Different susceptibility to SARS-CoV2 infection and variable clinical manifestations of COVID-19 might be associated with altered expression of ACE2-, CD147- and CD26- related genes in patients with risk factors and known comorbidities.