# Angiotensin-Converting Enzyme 2 as a Possible Correlation between COVID-19 and Periodontal Disease
## 1 Introduction  
SARS-CoV-2 is a novel coronavirus [1]. The spike proteins of this RNA virus bind to the cellular receptors of cells to mediate infection of their target cells, after which viral replication begins in the cytoplasm. The main targets of SARS-CoV-2 are the lungs, immune organs, heart, arteries, and, last but not least, the oral cavity, with involvement of the first upper airways (nasal cavity, paranasal sinuses, oral cavity, pharynx, epiglottis, and larynx.) [2]. The virus transmission path is linked to contact or faecal-oral transmission, coughing, and sneezing, as well as to respiratory droplets [3, 4]. The pivotal effect is that patients' symptoms are related to the onset of the disease [5] and contagiousness can persist for up to 2 or 3 weeks after convalescence [6, 7]. Moreover, patients' symptoms and disease manifestations are diversified for each person affected; indeed, mild or subclinical symptoms havebeen associated with infective patients [8]. Several aspects might facilitate the outspread of COVID-19. Predisposition, genetics, systematic diseases, population, gender, and age are key factors for the onset and progression of the viral infection, and patients suffering from asthma or pulmonary deficiency are more exposed to a high risk of mortality [9; 10]. Patients' origin might affect the infection response; indeed, recent studies showed a higher susceptibility in Asia, mainly in males, than in other continents such as Europe and America [6; 11]. Recently, a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), was isolated from a patient with COVID-19 [12], which is, convincingly, the functional receptor for SARS-CoV-2. Another study, before this discovery, showed the presence of ACE2 in various organs and tissues [13]. Indeed, from a sample of 93 patients with a mean age of 52 \(\pm\) 22 years and a gender ratio of 50/43, ACE2 was identified in type I and type II alveolar epithelial cells residing in both the nasal and oral mucosa, in the nasopharynx, in the smooth muscle cells and endothelium of vessels in the stomach and the skin, precisely in the basal cell layer of the epidermis extending to the basal cell layer of hair follicles, and in the basal layer of the non-keratinizing squamous epithelium [13]. The inflammatory manifestation can be dissimilar according to the key factors mentioned before and, consequently, ACE2 levels might also be different in each population. Thus, the onset and progression of the disease might show acute and aggressive sequel or subclinical symptoms [6; 11]. ACE2 is also an enzyme identified in COVID-free patients with periodontal disease in different cell types, such as fibroblasts, osteoblasts, and osteoclasts, that are involved in the bone and soft tissue remodelling around teeth and implants [14]. Furthermore, the role of this enzyme in response to the onset and progression of periodontal disease is clear [14]. The possible coexistence of COVID-19 and periodontitis could be a critical situation to observe and treat. The viral exacerbation associated with periodontal bacteria might facilitate cross-infections and mutual empowerment. This situation in patients with special needs might be fatal and a monitoring phase needs to be planned [15; 16]. ACE2 is related to the renin-angiotensin system (RAS) in which it has an indispensable role in counteracting ACE function. There are enhancers and diminishes in the regulation of functional activities and vital responses such as blood pressure, organ protection, inflammation response, oxidative stress, and diuresis. Their role is associated with other enzymes and receptors forming two opposite axes: the angiotensin-converting enzyme 2-angiotensin 1-7-Mas receptor (ACE2-Ang1-7-MasR) axis and the angiotensin-converting enzyme (ACE)e-angiotensin II(Ang II) -angiotensin receptor type 1(AT1) axis.