CRITICAL REVIEW Oral Pathology Orofacial manifestations of COVID-19: a brief review of the published literature Esam HALBOUB(a) Abstract: Coronavirus disease 2019 (COVID-19) has spread Sadeq Ali AL-MAWERI(b) exponentially across the world. The typical manifestations of Rawan Hejji ALANAZI(c) COVID-19 include fever, dry cough, headache and fatigue. However, Nashwan Mohammed QAID(d) atypical presentations of COVID-19 are being increasingly reported. Saleem ABDULRAB(e) Recently, a number of studies have recognized various mucocutaneous manifestations associated with COVID-19. This study sought to (a) Jazan University, College of Dentistry, summarize the available literature and provide an overview of the Department of Maxillofacial Surgery and potential orofacial manifestations of COVID-19. An online literature Diagnostic Sciences, Jazan, Saudi Arabia. search in the PubMed and Scopus databases was conducted to retrieve (b) AlFarabi College of Dentistry and Nursing, the relevant studies published up to July 2020. Original studies Department of Oral Medicine and published in English that reported orofacial manifestations in patients Diagnostic Sciences, Riyadh, Saudi Arabia. with laboratory-confirmed COVID-19 were included; this yielded 16 (c) AlFarabi College of Dentistry and Nursing, articles involving 25 COVID-19-positive patients. The results showed a Department of Oral Medicine and Diagnostic Sciences, Riyadh, Saudi Arabia. marked heterogeneity in COVID-19-associated orofacial manifestations. The most common orofacial manifestations were ulcerative lesions, (d) AlFarabi College of Dentistry and Nursing, Department of Restorative Dental Sciences, vesiculobullous/macular lesions, and acute sialadentitis of the parotid Riyadh, Saudi Arabia. gland (parotitis). In four cases, oral manifestations were the first signs of (e) Primary Health Care Corporation, Madinat COVID-19. In summary, COVID-19 may cause orofacial manifestations Khalifa Health Center, Doha, Qatar. that might be the initial features in several cases. However, the occurrence of orofacial manifestations in COVID-19 seems to be underreported, mainly due to the lack of oral examination of patients Declaration of Interests: The authors with suspected and/or confirmed COVID-19. Oral examination of certify that they have no commercial or associative interest that represents a conflict all suspected and confirmed COVID-19 cases is crucial for better of interest in connection with the manuscript. understanding and documenting COVID-19-associated orofacial manifestations. Corresponding Author: Keywords: COVID-19; Coronavirus; Oral manifestations, Review. Sadeq Ali Al-Maweri E-mail: [email protected] Introduction https://doi.org/10.1590/1807-3107bor-2020.vol34.0124 Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus 2019 disease (COVID-19) has caused an unprecedented global healthcare crisis. By the time of this writing, over 19 million people have been infected, and approximately 728,013 have lost their lives worldwide.1 While most cases are either asymptomatic or Submitted: July 9, 2020 affected with mild symptoms, a considerable fraction of cases develop Accepted for publication: September 28, 2020 Last revision: October 7, 2020 severe respiratory symptoms, leading to acute severe respiratory distress (ASRD) and sometimes multiple organ failure.2 Braz. Oral Res. 2020;34:e124 1 Orofacial manifestations of COVID-19: A brief review of the published literature The most commonly reported manifestations COVID-19 were included. Studies with suspected include fever, cough, sore throat, myalgia, arthralgia, COVID-19 cases were excluded. headache, dyspnea, and sputum production.2 However, an increasing number of atypical clinical presentations Data extraction have been reported, such as gastrointestinal symptoms, The following information was extracted and dermatological manifestations, and chemosensory tabulated: author, country of the study, number of dysfunctions.2,3,4 Interestingly, some studies have cases with orofacial manifestations, age, sex, orofacial found that taste and smell chemosensory dysfunctions manifestations, onset of the orofacial manifestations, were the initial and only signs of the disease in a any special investigations performed, treatment of considerable fraction of patients.3,5 Additionally, oral lesions, and signs and symptoms of COVID-19. more recent studies have reported clinical orofacial manifestations in COVID-19-positive patients, Results including oral ulcerative lesions,6 vesiculobullous lesions, and acute sialadenitis.7,8,9 Understanding the General characteristics of the orofacial manifestations of COVID-19 by dentists is included studies extremely important for the early detection of the Out of the 370 retrieved studies, only 16 articles disease and prevention of transmission. Although fulfilled the inclusion criteria. 4,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 a number of studies have reported on orofacial The 16 included studies (10 case reports and six case manifestations in patients with COVID-19, no attempt series) comprised 25 patients with laboratory-confirmed has been made thus far to review the available COVID-19.4,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 A full description of literature in this context. Therefore, the present the included cases is provided in Table 1. The number review sought to summarize the available literature of cases in the included studies ranged from one to four. and provide an overview of the potential orofacial Most of the studies were published during May and manifestations of COVID-19, as well as to highlight June 2020. The age of the participants ranged from 6 the implications for dental practitioners. to 77 years. Over half of the cases (61.1%) were females. With reference to COVID-19 diagnosis, all included cases Methodology in this review were confirmed with PCR; suspected COVID-19 cases were excluded. Approximately half Literature search and eligibility criteria of the subjects had one or more systemic diseases, e.g., A literature search was conducted in the PubMed diabetes mellitus, hypertension, or kidney problems. and Scopus databases for all relevant studies published Orofacial manifestations were the first clinical signs up to June 2020. The search was updated in July 2020 for of COVID-19 in four cases;10,12,16 in the remaining any additional studies. A combination of the following cases, the reported onset of orofacial manifestations keywords was used: (“oral manifestations” OR “oral in relation to COVID-19 general symptoms ranged lesions” OR “oral findings” OR “orofacial findings” OR from 3 to 31 days (Table). “orofacial manifestations” OR “orofacial lesions” OR “dental manifestations” OR “gingival findings” OR Orofacial manifestations “gingival manifestations” OR “periodontal findings” The orofacial manifestations were highly variable. OR “periodontal manifestations” OR “salivary The most common presentations were ulcerative lesions, glands” AND “COVID-19” OR “Coronavirus” OR vesiculobullous lesions, macular erythematous lesions, “SARS-CoV-2” OR “novel coronavirus disease”). The and acute parotitis. The most commonly affected full-text articles of all potential studies were obtained intraoral site was the hard palate, followed by the and evaluated for inclusion. The reference lists of the dorsum of the tongue and labial mucosa. The diagnosis relevant studies were also manually searched for of oral mucosal lesions was based on clinical features in additional studies. All studies that reported orofacial most of the included studies, with only three studies6,7,14 manifestations in patients with laboratory-confirmed having performed biopsies to confirm the diagnosis. 2 Braz. Oral Res. 2020;34:e124 Halboub E, Al-Maweri SA, Alanazi RH, Qaid NM, Abdulrab S Table. Characteristics of patients with COVID-19 with oral manifestations. Treatment of Sex, age Oral manifestations/site Differential Coronavirus symptoms Author/Year Cases (country) Special investigation oral lesions (General health) (Onset relative to COVID-19) diagnosis and treatment (Resolution time) Histopathology: diffuse Topical of: Several painful irregular edema with mucosal diphen-hydramine, ulcers varying in size, on a desquamation, along dexamethasone, Symptoms: fever, shortness red background of the whole with granulation and tetracycline, and of breath Case 1 (Iran) F, 56 ys (DM) hard palate Aphthous ulcer ulceration with invasion lidocaine (after of mono-nuclear cells. one week) Treatment: remdesivir, Serology: negative for Ansari et al., Onset: After day 5 azithromycin, and 7 herpes antibodies 2020 supportive treatment Several small painful ulcers, Diphenhydramine, Histopathology: with irregular margins on dexamethasone, identical to the Symptoms: hypoxia M, 75 ys red back-ground on the tetracycline, lidocaine Case 2 (iran) Aphthous ulcer first case. (Hypertension) anterior tongue (after one week) Serology: negative for Treatment: azithromycin and Onset: After one week herpes antibodies supportive treatment Irregular, nonpainful ulcer on Chaux-Bodard F, 45 ys NM (after 10 days) Symptoms: mild asthenia Case 1 (Frace) the dorsum of the tongue NM None et al., 202012 (Healthy) Onset: First sign Treatment: NM Blisters on the labial mucosa Hyaluronic acid and Symptoms: fever, diarrhea Martín and desquamative gingivitis CHX MW, F, 65 ys Carreras-Presas Case 1 (Spain) Viral enanthema None Treatment: lopinavir 8 (Hypertension) Prednisolone 30 mg et al., 2020 Onset: After 31 days 200 mg, ritonavir