The oral manifestations and related mechanisms of COVID-19 caused by SARS-CoV-2 infection

Abstract

Coronavirus disease 2019 (COVID-19) was reported to be associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, and patients present mostly with respiratory symptoms. There have been an increasing number of reports on oral manifestations, and some of these signs are informative in terms of identifying SARS-CoV-2 infection. The goal of present study was to review and synthesize the clinical characteristics and underlying mechanisms of COVID-19 oral manifestations, as well as to evaluate the factors influencing SARS-CoV-2 infectivity, in order to conduct further in-depth investigations and help clinicians diagnose COVID-19 patients exhibiting oral symptoms.

Keywords: ACE2 receptor; COVID-19; SARS-CoV-2; TMPRSS2; influential factors; oral manifestations.

FIGURE 1

Overview of COVID-19 oral manifestations. Dysgeusia, oral mucosal lesions and xerostomia are the main oral symptoms of COVID-19. SARS-CoV-2 infection of the CNS and/or taste buds is the main cause of dysgeusia. Oral mucosal lesions include aphthous-like lesions, herpes-like lesions, geographic tongue, plaque-like lesions, fungal infections, mucosal petechiae, HSV reactivation-related ulcers, oral herpes zoster, gingivitis and bleeding gums. The primary cause of xerostomia is SARS CoV-2 infection of salivary gland acinar cells and ductal epithelium.

FIGURE 2

Cell entry mechanisms of SARC-CoV-2. Spike protein (S), envelope protein (E), and membrane protein (M) are three major proteins on the membrane of SARS-CoV-2. Cell surface entry and endosome entry are two distinct SARS-CoV-2 entry mechanisms. ACE2 is the primary receptor for SARS-CoV-2 entrance into the oral cavity. Virus binding to ACE2 triggers the conformational changes of the S1 subunit, exposing the S2’ site, which is then cleaved by the membrane protease TMPRSS2/4/11D (Cell surface entry pathway). In the absence of TMPRSS2, ACE2-virus complex is internalized via endocytosis into endosome/endolysosome where the S2’ site is cleaved by Cathepsin B/L (Endosome entry pathway). The fusion peptide is exposed and fuses with the cell membrane. The viral genome is then released into the cytoplasm of the host cell. In the virus producing cell, Furin cleaves the S1–S2 boundary in the trans-golgi network, contributing to the virus assembly and maturation.