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

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 andPPIB), 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.

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

“…Despite the importance of determining precisely which entry receptors SARS-CoV-2 uses to infect human cells, there remains considerable uncertainty amid multiple claimed viral receptors with variable qualities of data behind them 9,[32][33][34][35] . We investigated one of the most prominent claims among these, that human BSG acts as an alternate receptor for the virus to interact with, which has been the topic of several studies, news and review articles, and a clinical trial 8,14,15,[36][37][38][39] . Our access to established tools and reagents from previous work studying BSG's role as a host receptor in Plasmodium infection allowed us to rapidly investigate BSG as a SARS-CoV-2 receptor.…”

“…Basigin represents an attractive medical target because therapeutic agents have already been developed that target basigin based on basigin's previously-established role as an essential host receptor for invasion of the malaria parasite Plasmodium falciparum 11,12 . The claim that basigin acts as a host receptor for SARS-CoV-2 has already featured in published articles discussing the prioritization of therapeutics 13 , and has been the subject of published analyses looking at basigin expression on the assumption that it serves as a viral entry factor [14][15][16] .…”

Immunology of COVID‐19: Mechanisms, clinical outcome, diagnostics, and perspectives—A report of the European Academy of Allergy and Clinical Immunology (EAACI)

“…118 Unfortunately, the mechanisms involved in the lymphocytopenia are still not known in SARS-CoV and SARS-CoV-2 patients. T cells can be infected through highly expressed CD147 14,15 or potentially through CD26, as ACE2 expression on lymphocytes is very low, 10 except in certain tissue-derived T cells. 119 It is yet unclear whether such infection is the reason of the death of infected T cells.…”

SARS-CoV-2 structural coverage map reveals state changes that disrupt host immunity

“…Three further matching structures showed interactions between spike (from MERS-CoV and BtCoV-HKU4) and host membrane receptor DPP4 (a.k.a. CD26), an aminopeptidase that SARS-CoV-2 may use (Y. to enter host immune cells (Radzikowska et al, 2020). If so, DPP4 and ACE2 may interact with spike at distinct but overlapping binding sites ( Figure 4B) -making this region a potential therapeutic target.…”