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

  1. Urszula Radzikowska
  2. Mei Ding
  3. Ge Tan
  4. Damir Zhakparov
  5. Yaqi Peng
  6. Paulina Wawrzyniak
  7. Ming Wang
  8. Shuo Li
  9. Hideaki Morita
  10. Can Altunbulakli
  11. Matthias Reiger
  12. Avidan U. Neumann
  13. Nonhlanhla Lunjani
  14. Claudia Traidl‐Hoffmann
  15. Kari C. Nadeau
  16. Liam O’Mahony
  17. Cezmi Akdis
  18. Milena Sokolowska

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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 ), and 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 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 to 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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  1. Version published to 10.1111/all.14429
  2. ScreenIT

    SciScore for 10.1101/2020.05.14.090332: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: All studies were accompanied by the relevant ethical permissions, given by the appropriate Institutional Review Board.
    Consent: Each control and diseased subject gave informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableBriefly, we performed in-depth curated analysis of HBECs (Control = 5, Asthma = 6, COPD =5), bronchial biopsies (Control = 16, Asthma = 22, COPD = 3, Non-obese = 20, Obese = 21, Normotension = 32, Hypertension = 9, Non-smoker = 19, Smoker = 21, Female = 14, Mal e= 27), BAL fluid (Control = 16, Asthma = 22, COPD = 2, Non-obese = 19 Obese = 21, Normotension = 31, Hypertension = 9, Non-smoker = 19, Smoker = 20, Female = 14, Male = 26), whole blood (Control = 17, Asthma = 21, COPD = 3, Non-obese = 20, Obese = 21, Normotension = 32, Hypertension = 9, Non-smoker = 19, Smoker = 21, Female = 14, Male = 27).

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Study subjects, samples and study description: We analyzed gene expression of SARS-CoV-2 receptors and related molecules’ (Table S1) in a broad range of tissues and immune cells from the human RNA-seq databases generated by our ex vivo and in vitro approaches in the Swiss Institute of Asthma and Allergy Research (SIAF), by our collaborators or from the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/).
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    http://www.ncbi.nlm.nih.gov/
    suggested: (GENSAT at NCBI - Gene Expression Nervous System Atlas, RRID:SCR_003923)
    All calculations between different conditions were done using the edgeR R package47.
    edgeR
    suggested: (edgeR, RRID:SCR_012802)
    Correlation plots were done using Python’s Seaborn library.
    Python’s
    suggested: (PyMVPA, RRID:SCR_006099)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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  3. Version published to 10.1101/2020.05.14.090332v1 on bioRxiv