key: cord-0995074-wtgv13jw authors: Farid, Huma; Khan, Madiha; Jamal, Shizrah; Ghafoor, Robia title: Oral manifestations of Covid‐19‐A literature review date: 2021-05-24 journal: Rev Med Virol DOI: 10.1002/rmv.2248 sha: 421ad235c7d22355004eab1619dd6867ae614874 doc_id: 995074 cord_uid: wtgv13jw Initially, it was reported that coronavirus 2019 disease (Covid‐19) affects respiratory, gastrointestinal and neurological systems, but the oral, olfactory and integumentary systems are also involved. This review discusses various oral manifestations of Covid‐19 reported in the literature along with possible underlying mechanisms. The reported manifestations include taste impairment, oral mucosal changes (petechiae, ulcers, plaque‐like lesions, reactivation of herpes simplex virus 1(HSV1), geographical tongue and desquamative gingivitis) and dry mouth. The prominent location for mucosal lesions are tongue, palate and labial mucosa. The exact pathogenesis of these oral symptoms is not known. Angiotensin‐converting enzyme 2 (ACE2) cell receptors are expressed in abundance on oral mucosa allowing severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) to infect them. Gustatory impairment along with olfactory changes is now listed as a symptom of Covid‐19 by the World Health Organization, but further research is needed to confirm a link between reported additional oral symptoms and Covid‐19. Dental professionals may encounter individuals with Covid‐19 and be called upon to identify various oral manifestations of this disease. anticoagulant therapy as soon as possible after emergence of these oral lesions. 12 As dental practices throughout the world have opened or are preparing to open, it is quite possible that dentists may encounter oral manifestations of Covid-19 in their patients. The objective of this review is to report various oral manifestation of Covid-19 described in the literature. This will help dental professionals to focus on detailed intraoral examination before initiating any dental treatment on Covid-19 suspected or confirmed patients. 3. Type of publications (letter to the editors, correspondence, case report, case series, observational studies, clinical studies, clinical trials and reviews). 1. The publications addressing Covid-19 symptoms in general or challenges in dentistry without reference to oral manifestations or oral symptoms. 2. The studies presenting oral mucosal changes without reference to 3. In cases, where both the review and research articles present in that review were retrieved, a review article was selected instead of individual studies (Duplication removal). Publications screening and selection was divided into two phases: an initial screening of titles and abstracts, and final screening of full-text publications. Authors (Huma Farid, Madiha Khan, Shizrah Jamal) independently screened the titles and abstracts of retrieved publications from the initial search strategy. In this stage, articles were included if they reported the above-mentioned keywords in title or abstract. Full-text reading was carried out at initial screening stage only if the content of the title/abstract was unclear or abstract was not provided. The initial screening phase was followed by full-text publication screening. In this phase, publications were screened and selected on the basis of pre-determined inclusion and exclusion criteria. There was no disagreement between the authors during screening process. Except for the taste impairment, all other oral manifestations were mostly reported in the form of cross sectional studies, letters to the editors, case reports or short communications. Due to scarcity of literature on this topic, we were not able to report a systematic review. Still to make a structured narrative review and ensured standardization, PRISMA flowchart was followed for Using the described search strategy, a total of 86 publications were retrieved. After removing the duplicate publications, the total number reduced to 62. These 62 publications underwent titles and abstract screening and 30 were selected for full-text screening. On fulltext review, 11 publications were excluded. In addition to the abovementioned exclusion criteria, at this stage, the studies that did not distinguish between olfactory and gustatory impairment and considered them one entity were excluded. Similarly, a publication with hypothesized oral manifestations that can arise as a result of Covid-19 was excluded. A total of 19 publications were selected. Among these, there was one systematic review and meta-analysis on gustatory changes associated with Covid-19. For the remaining oral manifestations, mostly case report, case series, letters to the editors and short communications were found. The summary of included publications including type of study, demographics of patients (age and gender), oral manifestations, treatment provided, duration of symptoms and Covid-19 confirmation status is presented in Table 1 . The reported oral manifestations are briefly discussed under the discussion section. Gustatory and olfactory changes can be the only symptom in mild cases of Covid-19 or the initial symptom in patients who ultimately present with more severe respiratory failure. The reported gustatory changes associated with Covid-19 are hypogeusia, dysgeusia and ageusia. 10, [13] [14] [15] [16] [17] The exact pathogenesis of SARS-CoV-2 and olfactory and gustatory dysfunction is not known. It is reported that angiotensin-converting enzyme 2 (ACE2) cell receptors are expressed in abundance on respiratory epithelium and oral mucosa especially tongue. 16, 18 SARS-CoV-2 has a great affinity for these receptors. 19, 20 Direct damage to nasal and oral epithelium and neuroinvasive nature of this virus can result in olfactory and gustatory disorders. It is reported that 95% of the cases with taste disturbances are secondary to olfactory dysfunction. 21 Olfactory dysfunction should be considered as a primary cause if patient complaints of both smell and taste disturbances. Most of the studies had considered smell and taste disturbances as a single entity rather than two separate entities. [22] [23] [24] In fact, it is often very difficult for the patient to delineate between taste and smell dysfunctions. There is a need to highlight Covid-19 cases presented with gustatory dysfunction (hypogeusia, dysgeusia and ageusia) in the absence of olfactory changes. Investigations such as whole mouth and spatial taste tests can be employed to identify the presence of gustatory dysfunctions along with localization of area of impairment and threshold sensitivity to a particular taste. 25 Type of study Dry mouth is also reported in association with Covid-19 positive patients. 13 We are thankful to Dr. Muhammad Saad Shinwari for his support and expert opinion while preparing the final version of the manuscript. Proposed mechanisms of oral mucosal lesion due to Covid-19. SARS-CoV-2, severe acute respiratory virus syndrome coronavirus 2; TNF, tumour necrosis factor A new coronavirus associated with human respiratory disease in China Coronaviridae study group of the International Committee on Taxonomy of Viruses. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 Severe Acute Respiratory Syndrome-related Coronavirus: The Species And its Viruses -A Statement of the Coronavirus Study Group. Biorxiv (Cold Spring Harb Lab) Coronaviruses: Methods and Protocols Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China Review of the clinical characteristics of coronavirus disease 2019 (COVID-19) Oral manifestation of Covid-19 as an inaugural symptom? Cutaneous manifestations in patients with COVID-19: a preliminary review of an emerging issue A new symptom of COVID-19: loss of Taste and smell Oral vesiculobullous lesions associated with SARS-CoV-2 infection Necrotizing periodontal disease: oral manifestation of COVID-19 Covid-19 symptomatic patients with oral lesions: clinical and histopathological study on 123 cases of the university hospital policlinic of bari with a purpose of a new classification COVID-19 from the perspective of dentists : a case report and brief review of more than 170 cases Tongue ulcers associated with SARS-CoV-2 infection: a case series The prevalence of olfactory and gustatory dysfunction in COVID-19 patients: a systematic review and meta-analysis. Otolaryngol Head Neck Surg Loss of smell or taste as the only symptom of COVID-19 Oral mucosal lesions in a COVID-19 patient: new signs or secondary manifestations? High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa Dysgeusia in COVID-19: possible mechanisms and implications. Oral Surg Oral Med Oral Pathol Oral Radiol Pathogenesis of dysgeusia in COVID-19 patients: a scoping review Smell and taste disorders in primary care COVID-19 anosmia reporting tool: initial findings Is gustatory impairment the first report of an oral manifestation in COVID-19? Self-reported olfactory and Taste disorders in patients with severe acute respiratory coronavirus 2 infection: a cross-sectional study Taste disorders: a review Anosmia, Hyposmia, and Dysgeusia Symptoms of Coronavirus Disease Center for Disease Control and Prevention. Symptoms of Coronavirus. 2020 World Health Organization. Coronavirus Disease (COVID 19) Pandemic Erythema multiforme-like eruption in patients with COVID-19 infection: clinical and histological findings A Phthalocyanine Derivate Mouthwash to Gargling/Rinsing as an Option to Reduce Clinical Symptoms of COVID-19. Case Series Oral Complications of ICU Patients with COVID-19 : Case-Series and Review of Two Hundred Ten Cases Oral lesions in Covid 19 positive patients Oral cavity lesions as a manifestation of the novel virus (COVID-19) Orofacial manifestations of COVID-19: a brief review of the published literature Association of viral infections with oral cavity lesions: Role of SARS-CoV-2 infection Oral manifestations in coronavirus disease 2019 (COVID-19) Oral manifestations in COVID-19 patients Oral erosions and petechiae during SARS-CoV-2 infection Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases Cutaneous signs in COVID -19 patients: a review Olfactory and oral manifestations of COVID-19: sex-related symptoms-A potential pathway to early diagnosis Comment on 'Cutaneous manifestations in COVID-19: a first perspective' by Recalcati S Symptomatology in head and neck district in coronavirus disease (COVID-19): a possible neuroinvasive action of SARS-CoV-2 Anosmia and dysgeusia in the absence of other respiratory disease: should COVID-19 infection be considered? No Title Oral cavity lesions as a manifestation of the novel virus (COVID-19) Oral manifestations of Covid-19-A literature review The authors declare no conflicts of interest. Robia Ghafoor provided advice to improve the manuscript.All authors have read and approved the submitted version. This is a narrative review and data sharing is not applicable to this article as no new data was created in this study. The analyzed data (studies included in the review along with variable of interest are presented in the Table 1 whereas literature search flow chart in presented in Figure 1 ). https://orcid.org/0000-0002-3297-5086Madiha Khan https://orcid.org/0000-0001-6474-842X