key: cord-0983146-5j04bqdw authors: El Kady, Dina M.; Gomaa, Esraa Ahmad; Abdella, Walid Shaban; Ashraf Hussien, Reham; Abd ElAziz, Rawda H.; Khater, Ahmad G. A. title: Oral manifestations of COVID‐19 patients: An online survey of the Egyptian population date: 2021-05-01 journal: Clin Exp Dent Res DOI: 10.1002/cre2.429 sha: 2278db7f11b886b0410e6b20d0c5c5eb16ba181b doc_id: 983146 cord_uid: 5j04bqdw OBJECTIVES: This pilot survey aims to study the oral manifestations associated with COVID‐19 infection and report the prevalence of oral signs and symptoms in COVID‐19 patients. MATERIALS AND METHODS: From May 15 to June 10, 2020, we used an online questionnaire containing the oral manifestations that are expected to be associated with the COVID‐19 infection. Adults in our survey who have been diagnosed with COVID‐19 positive were confirmed with reverse transcriptase PCR (RT‐PCR), and isolated in various hospitals in Cairo, Egypt. RESULTS: This pilot study included 58 (53.4% males and 46.6% females) COVID‐19 patients ages 18–46 years, and 13 (22.4%) were healthcare workers. Our results showed that 67.2% of the patients had at least one manifestation related to the oral cavity and salivary glands, and 32.8% (n = 19) did not have any symptoms associated with the oral cavity. The highest prevalence symptoms were dry mouth 39.7% (n = 23), gustatory dysfunction as 34.5% (n = 20) loss of salt sensation, 29.3% (n = 17) loss of sweet sensation, and 25.9% (n = 15) altered food taste, while the least prevalent symptoms were tongue redness 8.8% (n = 5), and gingival bleeding 7% (n = 4). The most frequently associated symptoms were loss of salt and sweetness, as reported by 27.6% of the participants. However, there was no significant association between the incidence of oral symptoms and demographic data (age, gender, or job) of the patients (p > 0.05). CONCLUSIONS: Based on limited data, COVID‐19 significantly impacts the oral cavity and salivary glands, as salivary gland‐related symptoms and taste disorders are highly prevalent in COVID‐19 patients. The novel coronavirus disease 2019 (COVID-19) is a human-to-human transmitted disease caused by one of the coronaviruses, which are a large family of viruses that can cause serious disorders such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS; Dar Odeh et al., 2020; Fini, 2020; Speth et al., 2020) . The World Health Organization (WHO) recognized COVID-19 as a pandemic disease, with most countries reporting significant numbers of infected people and deaths as of December 2019 (Organization, 2020). The typical clinical symptoms of COVID-19 patients were fever, cough, shortness of breath, and myalgia or weakness with abnormal chest CT, while the less prevalent symptoms were sputum formation, headache, hemoptysis, and diarrhea. Often, alteration or loss of taste and smell sensation has been observed (Guan et al., 2020; Huang et al., 2020; Lechien et al., 2020; Vinayachandran & Balasubramanian, 2020) . Coronavirus attacks human cells by angiotensin-converting enzyme 2 (ACE2) receptors since the current evidence indicated that ACE2 acts as the primary host cell receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; Zou et al., 2020) . As such, the virus will bind to ACE2 using the spike-like protein on its surface, and ACE2 will serve as a cellular portal for viral entry into the cell to cause COVID-19 infection (Ciaglia et al., 2020) . Hence, organs with high ACE2 expression (e.g., lung) can become target cells during SARS-CoV-2 infection that cause inflammatory reactions in related organs and tissues, such as salivary glands and tongue, which could explain the occurrence of both loss of taste and oral ulceration due to destruction of keratinocytes and oral fibroblasts . Otherwise, high viral load in the saliva and nasal secretion can be a pathogenic factor involved in developing the oral changes associated with COVID-19 infection, which indicates the direct effect of the virus on the oral tissues (Cruz Tapia et al., 2020) . On the other side, these effects may be attributed to the virus's indirect influence on the immune system, contributing to other opportunistic infections, such as recurrent herpes simplex virus (HSV-1) infection and oral ulcerations (Brandão et al., 2020; Dziedzic & Wojtyczka, 2020) . COVID-19 has two routes of transmission, either directly or indirectly. It can be transmitted indirectly through saliva, while it may be spread directly by coughing, sneezing, and droplet inhalation or via direct contact with oral, nasal, and ocular mucous membranes (Peng et al., 2020; Speth et al., 2020) . The oral cavity is known to be an indicative mirror reflecting the underlying health condition. Therefore, careful examination of the mouth will assist in early diagnosis and treatment since some oral symptoms (e.g., oral ulcerations, gingival bleeding, dry mouth, and oral discomfort, halitosis, burning sensation, or difficulty swallowing) that can be associated with certain systemic disorders (Chi et al., 2010) . Several studies have considered oral transmission to be one of the main routes of COVID-19 infection Hindson, 2020; Yeo et al., 2020) . Even though many studies addressed the validity of saliva in the COVID-19 diagnosis (Fernandes et al., 2020; Pedrosa et al., 2020; Sabino-Silva et al., 2020; , as well as the precautions and implications for dental practice during the COVID-19 pandemic era (Coulthard, 2020; Ge et al., 2020; Sabino-Silva et al., 2020; Spagnuolo et al., 2020) , there is still a gap of knowledge regarding the oral manifestations related to COVID-19 and its impact on the oral cavity. Therefore, this pilot survey aims to study the oral manifestations associated with COVID-19 infection and report the superiority of oral signs and symptoms in COVID-19 patients. We reported this pilot study based on the Checklist for Reporting (Table S1 ). Since it was not feasible to examine the patients clinically, and to avoid selection biases due to convenience sampling, all participants were volunteers to minimize the risk of bias. We included only adults diagnosed with COVID-19 positive, confirmed with reverse transcriptase PCR (RT-PCR), and are isolated in various hospitals in Cairo, Egypt, from May 15 to June 10, 2020. We used a Google Form to create an online questionnaire containing multiple manifestations that were to be associated with COVID-19 based on the available evidence. All symptoms included in this questionnaire were in four primary categories; the first category was the gustatory disorders described as a loss of salt sensation, loss of sweetness, and altered food taste. The second category was the symptoms associated with salivary glands infection described as dry mouth (i.e., hyposalivation), difficulty swallowing, pain or swelling in the submandibular gland area, and pain or swelling in the parotid gland area. The third category was the oral mucosal changes (i.e., oral lesions) described as oral ulcers, spots of mouth or lips, tongue redness, gingival bleeding, and burning sensation. The last category was the patients with no symptoms related to the oral cavity and salivary glands. We presented the categorical data as frequencies and percentages and analyzed using Fisher's exact test. The significance level was set at p ≤ 0.05 within all tests, and p-values were corrected for multiple comparisons using Bonferroni correction. Statistical analysis were conducted with Windows version 4.0.3 of the R software (Team, 2020). A total of 58 (53.4% males and 46.6% females) COVID-19 patients ages 18-46 years were included in this pilot study, while 13 (22.4%) were healthcare workers, and there were no significant differences in age or gender between participants (p = 0.094 and 0.580 respectively; Table 1 ). Our results found that 67.2% of the patients had at least one of the oral manifestations, while about 32.8% (n = 19) did not have any symptoms related to the oral cavity. The high prevalence symptom was dry mouth 39.7% (n = 23), followed by gustatory dysfunction as 34.5% (n = 20) loss of salt sensation, 29.3% (n = 17) loss of sweet sensation, and 25.9% (n = 15) altered food taste. The prevalence of symptoms associated with salivary glands infection was 22.4% (n = 13) difficult swelling, 13.8% (n = 8) pain or swellings in the salivary gland or cheek, and 10.3% (n = 6) pain or swelling below mandible. While the oral mucosal changes were less prevalent as 22.4% (n = 13) of burning mouth sensation, 17.2% (n = 10) of ulceration, 13.8% (n = 8) of mouth and lip spots, 8.8% (n = 5) of tongue redness, and 7% (n = 4) of gingival bleeding (Figure 1 ). The most associated symptoms were loss of salt and sweetness, as observed in 16 (27.6%) participants, while the dry mouth and gustatory impairment symptoms were often associated in 14 (27.6%) participants for each manifestation. However, the association between the tongue's redness either with lips or mouth spots, discomfort or swelling below the mandible, or gingival bleeding, was the least frequent, which occurred in one case ( Figure 2 ). However, there was no significant association between the incidence of oral symptoms and demographic data (age, gender, or job) of the patients (p > 0.05; Table 2 ). COVID-19 patients have a wide variety of signs and symptoms, so the study of these manifestations will contribute to the early diagnosis and isolation of infected patients (Vaira et al., 2020) . Also, COVID-19 as an acute infection with multiple therapeutic measures could adversely affect oral health leading to opportunistic infections (e.g., recurrent herpes simplex virus (HSV-1) infection and oral ulcerations) due to the compromised immune system and xerostomia associated with the reduced salivary flow (Dziedzic & Wojtyczka, 2020) . This pilot study revealed a high prevalence of salivary glandrelated symptoms supporting the beneficial effect of saliva on virus detection and the negative impact of saliva on viral transmission hypotheses (Han & Ivanovski, 2020; Xu et al., 2020) . The effect of COVID-19 on salivary glands was reflected in different ways: first patients complained of pain or swelling in either parotid or submandibular areas (13.8% and 10.3%, respectively), and second 39.7% suffered from a dry mouth. These findings indicates the protective role of saliva which continuously cleans the oral cavity and antiviral response against COVID-19 (Farshidfar & Hamedani, 2020; Malamud et al., 2011) . Hyposalivation might be a potential complication of chronic sialadenitis caused by COVID-19. As a repair mechanism following the inflammatory destruction of the salivary glands, this destruction could be repaired by fibrosis affecting both the acini and the duct leading to hypo-secretion. Hyposalivation raises the risk of inorganic salts deposition on the ductal wall that induces sialolithiasis contributing to stenosis and dilatation of the ducts . Respiratory infection incidence will then increase by enhancing virus adhesion and colonization and destroying the oral mucosa surfaces and airways, thus, decreasing antimicrobial peptides and proteins (Han & Ivanovski, 2020; Iwabuchi et al., 2012) . However, T-cell receptors for human pathogenic saliva can be the initial portal of the virus to the body; thus, the proliferation of the COVID-19 in the salivary gland may be responsible for the spread of infection from asymptomatic patients (Liu et al., 2011; Zhang et al., 2020) . As well, salivary glands can act as a harbor for a latent infection that can be reactivated later with a risk of chronic sialadenitis ; therefore, physicians should pay more attention to any variation in salivary glands or salivary secretions (Vinayachandran & Saravanakarthikeyan, 2020) . Taste loss (ageusia) occurs due to the viral infection to the olfactory cranial nerve or from rhinitis and nasal obstruction. The loss of smell (anosmia) is related to retro-nasal olfaction which is a sensory process, combining ortho-nasal smell and taste patterns and enabling people to perceive flavor. This mechanism is temporarily disrupted during upper respiratory infections due to mucosal inflammation and obstruction of the nasal passages, thereby physically blocking flavor and odor molecules from entering the olfactory cleft (Melley et al., 2020) . In this study, consistent with the current evidence, olfactory dysfunction was the primary factor identified either with or with- (Nokta, 2008) and is also reported in COVID-19 (dos Santos et al., 2020; Vinayachandran & Saravanakarthikeyan, 2020) . Concerning the oral ulceration (17.2%), mouth and lip spots (13.8%), their prevalence was higher than other oral changes which supports the case report of ulceration and skin rash in COVID-19 patients (Soares et al., 2020) . As such, many patients might have the same symptoms undetected due to the lack of oral examination by healthcare professionals (Martín Carreras-Presas et al., 2020) . Another case report of oral ulceration revealed that the history of the lesion was a 24-hr painful inflammation of the tongue papilla, followed by 24-hr erythematous macula, which evolved into irregular and asymptomatic ulcers; hence, many patients might not be aware of having oral ulceration due to lack of pain (Chaux-Bodard et al., 2020 Authors acknowledge the funding of article publication fees from the Egyptian Knowledge Bank (EKB). All authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. 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