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.