# Pathological changes in oral epithelium and the expression of SARS-CoV-2 entry receptors, ACE2 and furin

## TL;DR

This study found that oral tissues, even with pre-cancerous or cancerous changes, do not express ACE2, a key receptor for SARS-CoV-2, suggesting they are unlikely to be major entry points for the virus.

## Contribution

The study provides new evidence that oral epithelial pathologies do not increase susceptibility to SARS-CoV-2 infection due to lack of ACE2 expression.

## Key findings

- All oral mucosa samples, including normal and pathological tissues, showed no ACE2 immuno-expression or RNA transcripts.
- Furin expression was weak and mainly observed in dysplastic lesions but not in SCC.
- Patients with oral epithelial pathologies do not appear to be at higher risk for SARS-CoV-2 infection.

## Abstract

Expression of angiotensin-converting enzyme (ACE)-2 and co-factors like furin, play key-roles in entry of SARS-CoV-2 into host cells. Furin is also involved in oral carcinogenesis. We investigated their expression in oral pre-malignant/malignant epithelial pathologies to evaluate whether ACE2 and furin expression might increase susceptibility of patients with these lesions for SARS-CoV-2 infection.

Study included normal oral mucosa (N = 14), epithelial hyperplasia-mild dysplasia (N = 27), moderate-to-severe dysplasia (N = 24), squamous cell carcinoma (SCC, N = 34) and oral lichen planus (N = 51). Evaluation of ACE2/furin membranous/membranous-cytoplasmic immunohistochemical expression was divided by epithelial thirds (basal/middle/upper), on a 5-tier scale (0, 1—weak, 1.5 –weak-to-moderate, 2—moderate, 3—strong). Total score per case was the sum of all epithelial thirds, and the mean staining score per group was calculated. Real time-polymerase chain reaction was performed for ACE2-RNA. Statistical differences were analyzed by One-way ANOVA, significance at p<0.05.

All oral mucosa samples were negative for ACE2 immuno-expression and its transcripts. Overall, furin expression was weakly present with total mean expression being higher in moderate-to-severe dysplasia and hyperplasia-mild dysplasia than in normal epithelium (p = 0.01, each) and SCC (p = 0.008, p = 0.009, respectively).

Oral mucosa, normal or with epithelial pathologies lacked ACE2 expression. Furin was weak and mainly expressed in dysplastic lesions. Thus, patients with epithelial pathologies do not seem to be at higher risk for SARS-CoV-2 infection. Overall, results show that oral mucosae do not seem to be a major site of SARS-CoV-2 entry and these were discussed vis-à-vis a comprehensive analysis of the literature.