Journal of Orofacial Sciences

: 2021  |  Volume : 13  |  Issue : 1  |  Page : 73--81

Oral Manifestations of COVID-19 Patients: A Systematic Review

P. S. Karthika, R. Rathy, P. Jayanthi, R. K. Harish, M. Ameena, R. J. Krishnasree 
 Department of Oral Pathology and Microbiology, Azeezia College of Dental Science and Research, Meeyannoor, Kollam, Kerala, India

Correspondence Address:
Dr. P. S. Karthika
Department of Oral Pathology and Microbiology, Azeezia College of Dental Science and Research, Meeyannoor, Kollam, Kerala, India. Pincode: 691537


Introduction: The emergence of coronavirus disease 2019 (COVID-19) crisis has evoked an exigent need to explicate the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and oral mucosal lesions. The present systematic review aims to elucidate the recent literature on oral manifestations related to COVID-19 so as to help the dental professionals for better screening and early diagnosis of the disease. Materials and Methods: A comprehensive literature search on PubMed, Science direct, Scopus, and Embase databases was carried out from December 2019 to March 2021 using keywords “Coronavirus,” “COVID-19,” “SARSCoV-2,” “Oral mucosal lesions,” and “Oral manifestation.” Additional information was obtained from Cochrane, World Health Organization, and Medscape. The full text articles of case reports and cross-sectional studies were analyzed and included. The review included 25 articles. Results: Four most common oral manifestations were found: gustatory and olfactory dysfunction, xerostomia, oral mucosal lesions, and salivary gland diseases. Vasculitis, opportunistic infections, drug eruption secondary to administration of Non-Steroidal Anti-inflammatory Drugs (NSAIDs), stress, immunosuppression, and hyperinflammatory immune response secondary to COVID-19 might be some of the relevant predisposing factors responsible for the onset of oral manifestations in patients with COVID-19. Conclusion: The early detection of oral symptoms of SARS-CoV-2 infection could help the clinicians to perform a better screening, and in recognizing early manifestations of the disease. However, the oral manifestations might be misdiagnosed due to subsequent challenge of undergoing oral examinations, hence diverse studies should be undertaken by the researchers to gain a better insight into the topic.

How to cite this article:
Karthika PS, Rathy R, Jayanthi P, Harish RK, Ameena M, Krishnasree RJ. Oral Manifestations of COVID-19 Patients: A Systematic Review.J Orofac Sci 2021;13:73-81

How to cite this URL:
Karthika PS, Rathy R, Jayanthi P, Harish RK, Ameena M, Krishnasree RJ. Oral Manifestations of COVID-19 Patients: A Systematic Review. J Orofac Sci [serial online] 2021 [cited 2023 Jan 27 ];13:73-81
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Full Text


Coronavirus disease 2019 (COVID-19), an outbreak started in Wuhan, China, presents an imminent threat to global health. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a single-stranded RNA virus, belonging to Coronaviridae family, is the causative agent of the disease. SARS-CoV-2 virus particles are spherical with spikes projecting from the surface, binds, and fuses to the human cells which allow the virus to gain entry. Angiotensin-converting enzyme 2 (ACE2) receptor permits the attachment of the virus, their fusion, intracellular entry, and infection.[1] The disease primarily transmits via the respiratory droplets, and the signs and symptoms are apparent with an incubation period of 2 to 14 days, which include headache, fever, sore throat, dyspnea, dry cough, abdominal pain, vomiting, and diarrhea.[2],[3] World Health Organization (WHO) has named the disease “coronavirus disease 2019” or COVID-19 on February 11, 2020[4] and later declared as a “pandemic” on March 11, 2020 due to worldwide spread of the disease in a short period. Till date, WHO has reported 140,332,386 confirmed cases of COVID-19 globally, including 3,004,088 deaths.[5]

Recent investigations have suggested oral mucosa, chiefly the dorsum of the tongue and the salivary glands, as a possible route of SARS-CoV-2 infection.[6],[7] Several oral manifestations have been reported in patients with SARS-CoV-2 and studies are undergoing to confirm whether these signs and symptoms are due to the infections caused by coronavirus or because of secondary manifestations due to the underlying systemic illness. The review aims to elucidate various oral manifestations reported in patients diagnosed with COVID-19 so as to help the dental professionals for better screening and early diagnosis of the disease.

 Materials and Methods

The study was approved by the Institutional Review Board, Azeezia College of Dental sciences and Research, Kollam on 26th July 2020. A comprehensive literature search was made on PubMed, Scopus, Science direct, Embase databases from December 2019 to March 2021 using keywords “Coronavirus,” “COVID-19,” “SARSCoV-2,” “Oral mucosal lesions,” and “Oral manifestation.” Additional information was obtained from Cochrane, WHO, and Medscape. The reference list of relevant articles was searched for additional information. Inclusion criteria: The review included studies which reported oral manifestation of laboratory confirmed cases of COVID-19. Only full text articles were included. Exclusion criteria: Articles with suspected cases of COVID-19 infection were not considered. Literature reviews, articles from gray literature, and duplicate articles were not included in the review. In the initial phase of literature search, 424 articles were identified from databases of which 89 duplicates were removed, 335 articles remained for abstract screening, and based on inclusion and exclusion criteria, 48 articles were screened for full text. Finally, 25 articles were selected which met the inclusion criteria of which 22 were case reports and 3 were cross-sectional studies [Figure 1]. The quality of the selected studies was assessed using Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and cross-sectional studies [Table 1].{Figure 1}{Table 1}


When analyzing published case reports and cross-sectional studies, we observed four most common oral manifestations reported related to COVID-19 such as taste and smell alterations, xerostomia, oral mucosal lesions, and salivary gland disease that pose challenges in dental practice. The details including the author’s name, number of reported cases, age and sex of the patient, oral manifestations − signs and symptoms, comorbidities if present, duration of the disease, site of involvement, suggested etiology, investigations, and management of the disease were noted. The details are summarized in [Table 2].{Table 2}

Gustatory and olfactory dysfunction

Loss of taste (ageusia) and smell (anosmia) are the two early symptoms that are mostly encountered in patients with COVID-19. A study by Giacomelli et al.,[9] found either taste or olfactory disorders in 34% of patients with COVID-19 and 18.6% had both. Recently, Center for Disease Control and prevention had incorporated altered gustatory and olfactory perception in the key symptoms suggestive of COVID-19 infection. Altered taste sensation in COVID-19 varied from decreased sensitivity (hypogeusia), taste confusion (dysgeusia), or complete loss of taste (ageusia).[9],[10]


The most frequent oral manifestations observed among the patients with COVID-19 were amblygeustia (47.2%), xerostomia (46.3%), and 11.1% of the patients with dryness and inflammation of the oral cavity.[10] Yifan et al.[11] reported 10 most frequently encountered symptoms observed in patients diagnosed with COVID-19 were chest discomfort (31.4%), dyspnea (30.7%), nausea (21.4%), headache (19.3%), dizziness (17.9%), xerostomia (15.7%), fatigue (15%), sleepiness (9.3%), sweating (8.6%), and waist pain (7.1%). The decreased salivary flow might be caused by the SARS-CoV-2 infection of the salivary gland via the ACE2 receptors which provide intracellular entry and infection.[7]

Oral mucosal lesions

So far there have been limited number of cases published on oral mucosal lesions in association with COVID-19 infection, including aphthous-like lesions, herpetiform/zosteriform lesions, ulcerations and erosions, white/red plaques, papules or vesicles, petechiae or macules in the oral cavity.[12],[13] Among the oral lesions reported, ulcerative lesions were the most common. The involvement of both keratinized and nonkeratinized mucosa has been observed. Tongue was considered as the most common site of involvement followed by hard palate, buccal mucosa, lips, and gingiva. The complete remission of the oral symptoms occurred within 21 days. The researchers suggested the use of topical and systemic corticosteroids, antibiotics, and mouth washes for the management of oral mucosal lesions.

A case report of a 45-year-old female by Chaux-Bodard et al. presented an asymptomatic irregular ulcer on the dorsal aspect of the tongue. Initially the patient experienced a painful inflammation of the papilla of the tongue which gradually became an erythematous macule, later turns into an ulcer.[14] Another case of a 42-year-old male with a history of diabetes and hypertension, reported painful ulcers, and some petechial-like, small vesiculobullous lesion on the buccal mucosa.[15] The patient also observed multiple reddish macules dispersed on the hard palate, tongue, and lips. Ciccarese et al.[16] noticed ulcers and erosions on the lips, palate, and gingiva in a COVID-19 confirmed 19-year-old female. After the administration of antibiotic therapy, the patient had experienced a rapid onset of systemic illness along with skin and oropharyngeal lesion. Sakaida et al. observed erosive lesions on the lips and buccal mucosa in a 52-year-old female patient.[17] The patient was treated with antibiotics and Non-Steroidal Anti-inflammatory Drugs (NSAIDs). After the commencement of the treatment, erythema and erosions appeared on the lips in response to the administration of NSAIDs. Ansari et al.[18] observed the development of oral ulcerations in a 56-year-old female with diabetes mellitus and a 75-year-old male with hypertension. On the fifth day, the first patient complained of painful ulcers in the hard palate with irregular margins. And similar lesions were observed later in the other patient on the anterior of the tongue.

Aphthous-like lesion seems to appear on the oral mucosa of patients diagnosed with COVID-19 infection. A case report by Dos Santos et al.,[19] and a case series including eight cases by Brandao et al.[20] presented aphthous-like ulcers with/without necrosis, affecting the tongue, lips, palate, and oropharynx. Díaz Rodríguez et al.[21] reported three cases of patients with COVID-19 presenting with aphthous ulcers, burning sensation, tongue depapillation, and commissural cheilitis of which one of the patients presented pseudomembranous candidiasis and angular cheilitis. Corchuelo and Ulloa[22] diagnosed oral candidiasis and white and red plaques at the posterior border of the tongue in a 40-year-old female patient. In addition, dark brown pigmentation was also noticed in the gingiva. Jimenez-Cauhe et al.[23] reported three cases of female patients with a mean age of 66.75% with petechiae and macules related to erythema multiforme-like eruption in the palate. Another case report of two COVID-19-positive children observed fever, mucosal eruptions like COVID-19-associated Kawasaki disease and erythema multiforme.[24] The reported cases by Dos Santos et al., Díaz Rodríguez et al., Corchuelo and Ullo, Jimenez-Cauhe et al., Kämmerer et al., and Martín Carreras-Presas et al. described the potentiality of COVID-19 infection to contribute to adverse health conditions, which leads to opportunistic fungal infections, recurrent oral herpes simplex virus-1 infection, and herpetic gingivostomatitis.[19],[21],[22],[23]

A case series of four patients with COVID-19 presented minor aphthous ulcers. The author had noticed the common features such as the presence of one to more than five number of aphthae and mainly affects the younger patients.[27] Nonkeratinized mucosa was predominantly affected. A retrospective analysis conducted by Riad et al. detailed the presentation of aphthous stomatitis in 21 patients with COVID-19 on intraoral examination. Solitary ulcerations with a clearly defined erythematous margins were reported in the buccal mucosa (33.3%), tongue (14.3%), lower lip (14.3%), upper lip (14.3%), gingiva (9.5%), palate (9.5%), and both of palate and gingiva (4.8%).[28]

A case report of COVID-19 diagnosed 35-year-old female patient presenting with edema and erythema of the gingiva, necrosis of the interdental papillae with unprovoked gingival bleeding, but no detectable attachment loss.[29] The authors predicted a rapid increase in the prevalence of acute periodontal lesions during the pandemic. In a case report of Cruz et al., Angina bullosa-like lesion was noted presenting as an erythematous purple blister which appears asymptomatic on the tongue and hard palate of two patients with COVID-19.[30] Aghazadeh et al.[31] noticed systemic illness along with oral lesions like vesicles and erosions on the buccal mucosa and tongue and acral erythematous papular exanthema in a SARS-CoV-2 infected a 9-year-old female patient. Another case of a 51-year-old male presenting with widespread erythema on the hard palate and oropharynx with petechiae and pustules around the soft palate suggestive of enanthema due to COVID-19 were reported.[32] Hence, many authors considered viral enanthema as a possible challenge for prompt diagnosis and treatment.[33],[34] Recently, a case of painful palatal lesion was reported in a 50-year-old COVID-19-positive female patient with a history of type 2 diabetes. On investigation, COVID19-associated oral mucormycosis, a rare fungal infection, was confirmed.[35]

Salivary gland diseases

Recent studies have enunciated salivary gland involvement in COVID-19 infection. A study by Chen et al.[7] assessed ACE2 receptor expression in the epithelial cells of salivary gland and found the incidence of nCoV-2019 infection in the salivary glands. High viral loads as high as 75% were also detected in the saliva of critically ill patients. Fisher et al.[36] found a progressive unilateral swelling of face and neck in a 21-year-old female patient, along with systemic symptoms, diagnosed COVID-associated parotitis causing subjective malocclusion and trismus which favored bacterial etiology. Afsal et al.[37] reported salivary duct inflammation like Wharton duct in three patients with COVID-19 which gradually improved, and recovered completely within 2 weeks. The chances of occurrence of acute and chronic sialadenitis in patients with SARS-CoV-2 were suggested by Wang et al.[38] Decreased secretion of saliva associated with pain and tumor in the parotid and submandibular glands gradually caused the infections and stones in salivary ducts which could be an early manifestation associated with COVID-19 infections.[38]


Dental practitioners can play a major role in the early diagnosis and referral of affected patients and hence prevent the disease transmission. The review attempts to explain the association between various oral manifestations and SARS-CoV-2 infection. The actual prevalence is underestimated due to the lack of proper oral examination and documentation in these patients due to various reasons. Dysgeusia was the first recognized oral symptom which was reported in 38% of patients with COVID-19. According to the researchers, the presence of ACE2 receptors in the oral mucosa might be the cause for taste alteration in patients with SARS-CoV-2. A study by Xu et al. described higher expression of ACE2 on the tongue and in the epithelial cells of the salivary gland which was even higher than in the lungs.[6] Chemosensory dysfunction can occur as a separate entity or in combination. The exact pathophysiological mechanism leading to gustatory dysfunction in COVID-19 infection is yet unclear. Cyclic adenosine monophosphate, a universal second messenger has a key role in signal transduction of taste and smell. SARS-CoV-2 virus utilizes cyclic adenosine triphosphate (cAMP) for replication in oral and olfactory mucosa resulting in depleted level of cAMP and thereby resulting in taste and smell alterations in patients with COVID-19, hence utilized as a therapeutic target by preventing viral replication and thereby improving chemosensory dysfunction.[39]

Novel coronavirus can induce exanthematous lesions including ulcers, erosions, petechiae, vesicles, herpetiform/zosteriform lesions, aphthous-like lesions, white/red plaques, and erythema multiforme-like lesions in the oral cavity. The researchers suggested various contributory factors responsible for the occurrence of oral lesions related to SARS-CoV-2 infection. Some case reports suggested thrombotic vasculopathy secondary to COVID-19 disease might be a suggestive factor responsible for the patient presented lesions.[13] The presentation of macular erythematous lesions might be explained by COVID-19-related variable inflammatory reaction which leading to vasculitis.[14] Hence, irregular solitary oral ulcers could be an inaugural symptom of SARS–CoV-2 which has to be proved in large cohort studies. Ciccarese et al. detailed the pathogenesis of the occurrence of erosions and ulcerations as a consequence of the cytokine storm caused by the viral infection which could result in a hypercoagulability with the activation and consumption of endothelial cells and platelet. The viral particles attacking the bone marrow decreases the platelet production and the use of antimicrobial agents could further reduce the platelet count and, hence, worsen the disease.[16]

A study by Sakaida et al. mentioned erosions on lips and buccal mucosa which was clinically diagnosed as drug eruption in response to the administration of NSAIDs. This might be associated with cytokine storm induced by COVID-19 with dysregulation of Th17 resulting in chronic inflammatory response.[17] Some reports suggested the relevance of stress induction and immunosuppression in patients with COVID-19 resulting in impaired immune system that could potentially contribute to opportunistic fungal infections, recurrent oral herpes simplex virus-1 infection, and herpetic gingivostomatitis.[19],[21],[22],[23] The increased levels of inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin-1 (IL-1), and arachidonic acid metabolites in the basal layer of keratinocytes might be the reason for the postinflammatory pigmentations.[22] Necrotizing periodontal disease was observed in patients diagnosed with COVID-19.[29] Metagenomic analyses of patients with SARS-CoV-2 frequently detected high bacterial loads of Prevotella intermedia, a major causative agent for several acute periodontal lesions, along with Fusobacterium and Treponema species.[40] Recently mucormycosis otherwise called black fungus, a rare fungal infection, has been reported across many states in India and has affected at least 7250 people in India and 9 new cases are under treatment in the state of Kerala.[41] The disease is considered to be associated with immunosuppressive treatment of COVID-19 which frequently infects the sinus and later progresses into the orbit and cranium. Uncontrolled diabetes and postinflammatory immune response to COVID-19 treatment might be the predisposing factors for the disease.[35] Hence early diagnosis and intervention of oral diseases especially mucormycosis are of utmost importance to reduce the morbidity and mortality.

The dental practitioners often fail to identify the oral lesions associated with coronavirus infection due to limited knowledge and practice. The major challenge is whether the oral manifestations reported are due to direct manifestation of COVID infection or because of indirect presentations such as immunosuppression or medications used in treating COVID infection. As there were limited literatures pertaining to the topic, large-scale observational studies should be considered for better output.


The SARS-CoV-2 infection has turned out to be an important public health crisis around the globe. The occurrence of oral signs and symptoms should be considered that may vary significantly among the patients with COVID-19. Systemic illness/comorbidities in association with/without poor oral health conditions might be some of the contributory factors that can increase the risk of the disease. Oral healthcare professionals are often the first-line diagnosticians who can identify the oral symptoms associated with the pandemic. Hence, the need of the hour is to emphasize the importance of educating dental professionals on the latest protocols to manage oral manifestations related to COVID-19 infection for early diagnosis and better prognosis, and an extensive research is necessary to understand in-depth the association between oral manifestations and COVID-19 disease.

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Conflicts of interest

There are no conflicts of interest.


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