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Journal of Oral Biology and Craniofacial Research logoLink to Journal of Oral Biology and Craniofacial Research
. 2022 Mar 19;12(2):279–283. doi: 10.1016/j.jobcr.2022.03.008

Oral manifestations associated with COVID-19 disease: An observational cross sectional study

Jitendra Chawla a, Navaneeth Y a, Satvinder Singh Bakshi b, Vinoth Kumar Kalidoss c, Shikha Yadav a,, Swapnika Polineni a, Cheranjeevi Jayam a
PMCID: PMC8934178  PMID: 35340816

Abstract

Objectives

The aim of present study was to investigate oral manifestations associated with COVID-19 disease.

Materials and methods

This cross-sectional study comprised 367 suspects with mild/moderate COVID-19 symptoms who reported to a tertiary care hospital's screening OPD. An in-depth case history was taken, and an oral cavity examination was performed to detect any oral findings. All participants were tested for SARS-CoV-2 using a naso-pharyngeal swab and reverse transcription polymerase chain reaction.

Oral manifestations and the results of RT-PCR testing were correlated. Statistical analyses were performed using Epi Info and R software. To estimate the prevalence of oral symptoms, the Pearson chi-square test was used.

Results

Oral manifestations were found in 58% of the study population. The difference in the prevalence of oral manifestations between RT-PCR positive COVID-19 patients versus RT-PCR negative suspects was statistically significant (p = 0.007) with xerostomia and dysgeusia being significantly higher in positive patients (p = 0.036 and p = 0.044 respectively) while the prevalence of stomatopyrosis and other intraoral signs was insignificant.

Conclusion

Xerostomia and dysgeusia are the common oral manifestations of COVID-19.

Keywords: COVID-19 disease, Dysgeusia, Oral manifestations, RT-PCR, SARS-CoV-2, Xerostomia, Stomatopyrosis

Highlights

  • First cross sectional study on oral manifestations of COVID-19 disease.

  • Xerostomia and dysgeusia are the most common oral manifestations of COVID-19 disease.

  • Oral ulcers and lesions present in COVID-19 patients are non-specific and not related to COVID-19 disease.

  • Xerostomia and dysgeusia along with any systemic symptom like fever have more probability of suffering from COVID-19.

1. Introduction

COVID-19 disease was first detected in Wuhan, China in December 2019, and the disease's global spread prompted WHO to designate it as a global pandemic on March 11, 2020. This disease is caused by the enveloped RNA beta corona virus named Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). The SARS-CoV-2 virus disease, which began as a pneumonia outbreak in China, has now spread rapidly throughout the globe. As of April 1, 2021, there are around 128,540,982 cases globally with roughly 2,808,308 recorded deaths, and India is one of the most affected nations, with approximately 12 million cases.1

The SARS-CoV-2 virus encodes four major structural proteins namely the spike protein, the membrane protein, the envelope protein, and the nucleocapsid protein. The spike protein protruding from the surface of SARS-CoV-2 is a Type I glycoprotein that binds to specific host cell receptors (metallopeptidase named Angiotensin-Converting Enzyme 2) via a receptor-binding domain facilitating its entry into the target cells. A positive correlation between ACE-2 and CoV-1 has been observed. Genomic and structural studies have shown that the receptor-binding domain of SARS-CoV-2 exhibits similar molecular characteristics as that of SARS-CoV-1.2 COVID-19 disease may be asymptomatic or may present itself with mild and common symptoms like fever, dry cough, altered taste and smell sensation to severe symptoms like difficulty in breathing, chest pain, etc. A flurry of studies have reported oral manifestations such as oral ulcers, vesiculobullous lesions, erythematous macules, papules, dysgeusia, and xerostomia.3, 4, 5, 6 Oral mucosa may be the first area to get infected with SARS-CoV 2 virus. Thus, oral manifestations could be suggestive of COVID-19 and may help us in early identification and management. Scientific data search mostly led us to cross-sectional studies that have either been questionnaire-based or have included patients who are already on COVID-19 treatment or had no comparison group.7, 8, 9 The present cross-sectional study was designed to estimate the prevalence of oral manifestations amongst COVID-19 suspects and compare the same between RT-PCR positive COVID-19 patients and RT-PCR negative COVID-19 suspects.

2. Materials and methods

This observational cross-sectional study was conducted in suspected COVID-19 patients10 reporting to the Out Patient Department of the tertiary care hospital between September and December 2020. Patients with preexisting complaints of xerostomia and stomatopyrosis (of the duration ≥2 weeks prior to their hospital visit) and those requiring supplemental oxygen therapy were excluded from the study. The study was approved by the Institutional Ethics Committee in compliance with the Helsinki declaration and written informed consent was obtained from each participant. A case report from Israel concluded that 56.3% of COVID-19 patients showed oral manifestations.4 Considering this prevalence with 5% absolute precision and 95% confidence level, the sample size was calculated to be 367 using OpenEpi version 3.01 software.

A thorough case history was obtained from each patient including their demographic details, tobacco usage, and comorbidities like diabetes mellitus, hypertension, etc. Details about symptoms of viral respiratory infection such as cough, fever, myalgia, sore throat, nasal congestion, running nose, etc. were elicited from all the participants. Patients were also enquired about oral symptoms such as altered taste sensation (dysgeusia), feeling of dry mouth (xerostomia) and burning sensation in the oral cavity (stomatopyrosis) using standardized questionnaires.11,12 Following this all patients underwent thorough intraoral examination, following proper biosafety guidelines, by the authors to detect the presence of intraoral signs like ulcers, erythema, macules, papules, etc. All the details were recorded in a case history sheet. After examination patients were tested for SARS CoV-2 with RT-PCR using nasopharyngeal swabs. RNA was extracted from the clinical samples with a QIAamp viral RNA mini kit (QIAGEN, Hilden, Germany) following the manufacturer's instructions at the COVID-19 virus research diagnostic laboratory of the institute. Depending upon the results of RT-PCR, the participants were divided into two study groups i.e., RT-PCR positive COVID-19 patients (SG-1) and RT-PCR negative COVID-19 suspects (SG-2). Results of RT-PCR tests and oral findings were further correlated.

Data entry was done in Microsoft Excel spreadsheet and analysis was done using Epi info and R software. Categorical variables like prevalence of oral manifestations, results of RT-PCR tests, comorbidities, etc. were summarized as frequency and percentage. For subgroup analysis of categorical variables, chi-square test was used. Logistic regression was used for estimating the adjusted odds ratio (OR) with 95% confidence interval. The 95% confidence interval (CI) and p-value for each OR were tabulated. p < 0.05 was considered statistically significant.

3. Results

Amongst 367 COVID-19 suspects included in the study, 60% (n = 217) of the study participants were RT-PCR positive COVID-19 patients (Table 1). More than half of the participants were less than 50 years of age and 70% of the study participants were males. One in every four of the study participants had a history of at least one comorbidity like hypertension, coronary artery disease, diabetes mellitus, bronchial asthma and the same distribution was found in each of the two study groups. 6% of study participants had a history of tobacco smoking and 2% were users of smokeless tobacco.

Table 1.

Demographic and Risk factor profile of study participants.

Item Sub-group COVID Positive (n = 217) COVID Negative (n = 150) Total (n = 367) p-value
Age Group 18–49 years 112 (51.6) 89 (59.3) 201 (54.8) 0.341
50–60 years 80 (36.9) 47 (31.3) 127 (34.6)
60-years 25 (11.5) 14 (9.3) 39 (10.6)
Gender Male 155 (71.4) 102 (68.0) 257 (70) 0.481
Female 62 (28.6) 48 (32.0) 110 (30)
Medical Comorbidities Yes 57 (26.3) 35 (23.3) 92 (25.1) 0.524
No 160 (73.7) 115 (76.7) 275 (74.9)
Smoking Yes 11 (5.1) 11 (7.3) 22 (6.0) 0.369
No 206 (94.9) 139 (92.7) 345 (94.0)
Smokeless Tobacco Use Yes 6 (2.8) 2 (1.3) 8 (2.2) 0.356
No 211 (97.2) 148 (98.7) 359 (97.8)
Total 217(59.1) 150(40.9)) 367(100)

The clinical features of study participants have been represented in Table 2. Out of 176 study participants who had fever, 121 (55.8%) were RT-PCR positive, and 55 (36.7%) were RT-PCR negative, this difference is statistically significant (p-value= <0.001). 30% of all the participants had cough, 20% had sore throat, 7% had shortness of breath and 11% had other symptoms like running nose, headache, and myalgia. 58% of the study population had oral manifestations such as xerostomia, dysgeusia, stomatopyrosis, intraoral signs like ulcers, erythema, etc. The prevalence of any one of the oral manifestations amongst RT-PCR positive patients (64%) and RT-PCR negative suspects (50%) had a statistically significant difference. Xerostomia (38%) was the most common oral manifestation followed by dysgeusia (32%). There was a statistically significant difference in the prevalence of xerostomia (SG1-42.9%; SG2-32%) and dysgeusia (SG1-35.9%; SG2 26%) between the two study groups. Amongst the participants, 18% had stomatopyrosis, 13% had intraoral signs like macula, whitish patch, vesicle, erythema, and 3.7% had oral ulcers, the prevalence of these findings did not have a statistically significant difference (Table 3).

Table 2.

Clinical features of study participants.

Symptoms COVID Positive (n = 217) COVID Negative (n = 150) Total (n = 367) p-value
Fever 121 (55.8) 55 (36.7) 176 (48.0) <0.001*
Cough 67 (30.9) 45 (30.0) 112 (30.5) 0.858
Sore throat 33 (15.2) 41 (27.3) 74 (20.2) 0.004*
Shortness of Breath 316 (7.4) 15 (10.0) 16 (7.4) 0.374
Other Symptoms like running nose, cold, headache. 32 (14.7) 11 (7.3) 43 (11.7) 0.030*
Oral Manifestations 139 (64.1) 75 (50.0) 214 (58.3) 0.007*

Table 3.

Oral manifestations among the study participants.

Symptoms COVID-19 RT-PCR Positive (n = 217) COVID-19 RT-PCR Negative (n = 150) Total (n = 367) p-value
Xerostomia 93 (42.9) 48 (32.0) 141 (38.4) 0.036*
Dysgeusia 78 (35.9) 39 (26.0) 117 (31.9) 0.044*
Stomatopyrosis 44 (20.3) 22 (14.7) 66 (18.0) 0.169
Signs In Oral Cavity 37 (17.0) 23 (15.3) 60 (16.3) 0.747

Table 4 presents the univariate and multivariate regression analysis and risk estimation of clinical symptoms for COVID-19 infection amongst the study participants. The clinical features like fever (OR 2.2), oral manifestations (OR 1.7), and other symptoms (OR 2.2) like running nose, headache, and body ache were found to have a significant positive association with COVID-19 infection. Multivariate regression analysis shows fever (Odds Ratio 2.2), oral manifestations (OR 1.6) and other symptoms (OR 2.7) were associated with COVID-19 infection independently. The odds of RT-PCR positive cases having fever was 2.2 (1.4–3.3) times higher than the RT-PCR negative suspects. The odds ratio increased to 2.3 when the participant had fever and anyone of the oral manifestations. Similarly, the odds ratio for cough (1.1) and sore throat (0.4) increased to 1.6 and 0.6 respectively. Table No 5 summarizes the distribution of intraoral signs amongst study participants.

Table 4.

Risk estimation of clinical symptoms for COVID-19 infection amongst the study participants.

Symptoms Unadjusted Odds Ratio (95% CI) Adjusted Odds Ratio (95% CI) Odds Ratio (95% CI) of Symptoms combined with Oral Manifestations
Fever 2.2 (1.4–3.3) 2.2 (1.4–3.5) 2.3 (1.4–3.6)
Cough 1.1 (0.6–1.6) 1.2 (0.7–1.9) 1.6 (0.9–2.7)
Sore throat 0.4 (0.3–0.79) 0.4 (0.3–0.8) 0.6 (0.3–1.2)
Breathlessness 0.7 (0.3–1.4) 0.7 (0.3–1.6) 0.6 (0.2–1.4)
Other Symptoms 2.2 (1.1–4.4) 2.7 (1.3–5.9) 1.3 (0.5–3.1)
Oral Manifestations 1.7 (1.2–2.7) 1.6 (1.1–2.5)

Table 5.

Distribution of intraoral signs amongst study participants.

Type of oral lesion Location of intraoral lesions Age in years Extraoral symptoms/comorbidities Laboratory confirmation of SARS-CoV-2
Erythema Uvula 27 Fever RT-PCR Positive
Floor of mouth and palate 21 Fever RT-PCR Positive
Palate and bilateral buccal mucosa 50 Fever, cough and sore throat RT-PCR Positive
Soft palate 58 Cough and sore throat with diabetes mellitus and hypertension RT-PCR Positive
Hard Palate 33 Loss of smell RT-PCR Positive
26 Running nose RT-PCR Positive
31 Cough RT-PCR Positive
32 Cough and sore throat RT-PCR Positive
58 History of close contact with a laboratory RT-PCR Positive COVID-19 patient RT-PCR Positive
55 Cough and sore throat with coronary artery disease and hypertension RT-PCR Positive
67 History of close contact with a laboratory RT-PCR Positive COVID-19 patient throat with diabetes mellitus and hypertension RT-PCR Positive
73 Fever with diabetes mellitus and hypertension RT-PCR Positive
Pharynx and tonsillar area 40 Fever RT-PCR Positive
42 Fever with history of smokeless tobacco use RT-PCR Positive
60 Fever with history of smoking tobacco RT-PCR Positive
63 Fever RT-PCR Positive
Tongue 55 Fever and cough RT-PCR Positive
Corner of mouth 40 Fever and cough RT-PCR Positive
Palate 73 Fever with diabetes mellitus and hypertension RT-PCR Negative
54 Sore throat RT-PCR Negative
25 Difficulty in breathing with history of smoking tobacco RT-PCR Negative
40 Fever RT-PCR Negative
42 Difficulty in breathing RT-PCR Negative
38 Fever RT-PCR Negative
30 Fever, cough and sore throat RT-PCR Negative
54 Fever. Sore throat, difficulty in breathing, running nose with history of hypertension and bronchial asthma RT-PCR Negative
45 Breathing difficulty RT-PCR Negative
Pharynx and tonsillar area 27 Cough RT-PCR Negative
46 Fever and sore throat RT-PCR Negative
Ulcer Palate 59 Fever and headache, hypertension and diabetes mellitus RT-PCR Positive
56 Breathing difficulty, hypertension and diabetes mellitus RT-PCR Positive
40 Fever RT-PCR Positive
68 Fever and breathing difficulty, Coronary artery disease, hypertension and diabetes mellitus RT-PCR Negative
Tongue 54 Cough RT-PCR Positive
52 Fever and cough, coronary artery disease and diabetes mellitus RT-PCR Positive
Buccal mucosa 21 Fever and cough RT-PCR Positive
42 Fever and sore throat RT-PCR Negative
Lower labial mucosa 41 Fever RT-PCR Positive
43 Fever and sore throat RT-PCR Negative
Floor of mouth 27 Fever, cough and sore throat RT-PCR Positive
Uvula 27 Fever RT-PCR Positive
29 Asymptomatic with close contact RT-PCR Negative
Whitish Patch Bilateral buccal mucosa 47 Fever with history of smokeless tobacco use RT-PCR Positive
Buccal mucosa 33 Fever, cough and sore throat RT-PCR Positive
Bilateral retromolar trigone region 61 Fever with hypertension RT-PCR Positive
Lower left alveolar ridge 70 Fever with hypertension with history of smokeless tobacco use RT-PCR Positive
Right retromolar trigone 60 Breathing difficulty with diabetes mellitus and hypertension with history of smokeless tobacco use RT-PCR Positive
Tongue, buccal mucosa 78 Fever with hypertension RT-PCR Positive
Floor of mouth 68 Fever and cough with hypertension RT-PCR Negative
Buccal mucosa 50 Fever with hypothyroidism RT-PCR Negative
Bilateral buccal mucosa 35 Fever, cough and sore throat RT-PCR Negative
Ventral surface of tongue 60 Fever, cough and sore throat with hypertension RT-PCR Negative
Whitish patch with oral submucous fibrosis Buccal mucosa bilateral 61 Fever with hypertension along with history of smoking and smokeless tobacco use RT-PCR Positive
Angular cheilitis Corner of mouth 40 Cough and hypothyroidism RT-PCR Positive
Inflamed bilateral Stenson's duct Stenson's duct 54 Fever with hypothyroidism RT-PCR Positive
Swelling in pharynx Pharynx 42 Fever, cough and sore throat RT-PCR Positive
Vesicles Palate 46 History of close contact with laboratory RT-PCR Positive covid-19 patient RT-PCR Positive
Bald tongue Tongue 58 Fever with diabetes mellitus RT-PCR Negative
Tonsillar hyperplasia Palate 37 Fever, cough and sore throat RT-PCR Negative
Bilateral ecchymosis Palate in greater palatine foramina region 63 Fever with hypertension and bronchial asthma RT-PCR Negative
Melanin pigmentation Tongue 30 Breathing difficulty with hypertension and diabetes mellitus RT-PCR Negative

4. Discussion

COVID-19 is provisionally diagnosed based on clinical findings ranging from fever, cough, cold, loss of smell, to acute respiratory distress syndrome. As there is a global surge in the individuals suspected of having COVID-19, signs and symptoms that are strongly linked to the disease would aid in early diagnosis. The present study assessed oral manifestations found in the suspects of COVID-19 disease.

Out of 367 study participants, 217 were RT-PCR positive, and 139 of them had at least one of the oral manifestations such as xerostomia, dysgeusia, stomatopyrosis, or intraoral signs such as oral ulcers, erythema, macule, or papule. The most common oral symptom was xerostomia, followed by dysgeusia. Erythema was the most common intraoral sign in 37 patients, followed by ulcers and a whitish patch.

Considering ACE-2 as a critical receptor for the SARS CoV-2 virus, ACE-2-expressing epithelial cells in the major and minor salivary glands may prove to be a target for the virus. Since, salivary glands serve as a substantial reservoir for this virus, it can be detected in the saliva even before respiratory symptoms appear.13 Virus can also be obtained from saliva samples early in the disease and via ductal openings of salivary glands at a later stage.14 These findings suggest that the oral symptoms may be caused by viral interference with the salivary flow. In our study, 93 (42.9%) RT-PCR positive patients reported xerostomia, compared to 48 (32%) RT-PCR negative patients. Stomatopyrosis, which was found in 20% of confirmed cases and 14.7% of suspects, might be linked to xerostomia. A case series of 140 RT-PCR positive patients, 56% of whom reported xerostomia, yielded similar results.4 Francesco Freni et al. used the summated Xerostomia Inventory-Dutch Version (SXI-DV) questionnaire to assess xerostomia in 50 RT-PCR positive patients and found dry mouth in 32% of them.15

The increasing load of gustatory dysfunction in COVID-19 patients has led to the estimated global pooled prevalence of dysgeusia to 41.47%.16 Sialic acid is a fundamental component of the salivary mucin and it protects the glycoproteins that convey gustatory molecules inside the taste pores from premature enzymatic degradation. A reduction of sialic acid in the saliva is associated with an increase in the gustatory threshold.17 Millanetti M et al. has suggested that spike protein of SARS-CoV-2 could also interact with sialic acid receptors, in addition to the known interaction with ACE-2.18 Thus, it can be hypothesized that dysgeusia may be secondary to accelerated degradation of the gustatory particles.19 In our study we observed that 117 patients reported dysgeusia out of which 78 were RT-PCR positive.

The presence of vesiculobullous lesions on the skin and mucous membranes of COVID-19 patients have been supported by the immunohistochemical studies suggesting the presence of ACE2 receptors in the skin and mucous membranes including oral mucosa.20 Data on intraoral signs in COVID-19 patients which have been published till now are limited to case reports and series only.21 Carmen Martin Carreras Presas et al. reported 3 cases, in which 2 were suspects and one case was confirmed COVID-19 patient. All patients were having pain, oral ulcers, or blisters before seeking medical advice and they suggested that intraoral lesions may often be misdiagnosed due to the lack of intraoral examination.5 C D Soares et al. also reported a case with vesiculobullous lesions on the lips with erythematous halo and published it as the first report showing the SARS‐CoV‐2 spike protein, on immunohistochemistry in oral lesions of COVID‐19 patients.22 Favia et al. examined 123 diagnosed and hospitalized moderate to critical COVID-19 cases for oral lesions and categorized them based on when the lesions appeared. Early lesions in the initial stages of Covid-19 before the initiation of treatment were observed in 65.9% of the patients and inferred that the appearance of oral lesions might be an early indication of peripheral thrombosis.9

Intraoral signs in COVID-19 may occur as ulcers,3,22,23 aphthae24 and maculae. It is still unclear whether the reported cases were related to the COVID 19 infection, unrelated occasional phenomenon or indirectly related occurrence associated with stress, anxiety and co morbidities. Systematic review on oral manifestations in COVID-19 reveals the triad of xerostomia, taste dysfunction, and oral mucosal lesions as prevalent manifestations, with xerostomia being the most common oral symptom and oral lesions having moderate certainty of evidence.8

Most of the available literature on oral lesions is published as case reports or series in moderate or severe cases already under COVID-19 treatment. Data for hospitalized patients was collected through medical records rather than directly from the patients, therefore some data may be incomplete. Lesions in some cases may be related to treatment or sequelae of the disease in severe cases. Questionnaire-based research did not include an objective evaluation by a qualified expert which may have led to bias. Since we have examined each patient and have found low prevalence of intraoral signs (13% in SG1; 3.7% SG2) in suspects of COVID -19, we conclude intraoral signs like ulcers, erythema, etc. in COVID-19 disease may be nonspecific and unrelated to disease. If there would have been any association between oral ulcers and infection with SARS CoV-2, it would have been reported by most patients as oral ulcers are usually very painful and interfere with everyday activities. As the patients have reported anosmia and dysgeusia, it seems quite improbable that they would have missed out on reporting painful oral lesions like ulcers.

The incidence of mucormycosis in COVID-19 patients has increased dramatically, particularly during the second wave of the pandemic, which may be associated with aggressive use of corticosteroids and uncontrolled blood sugar levels.25 We did not come across any patients who had mucormycosis like symptoms may be because, examination was done prior to the initiation of treatment for COVID-19.

The current study's strength is the relatively high number of study participants who were assessed and evaluated for oral symptoms of SARS CoV-2 infection in all suspects, whether symptomatic or asymptomatic. Because this is cross-sectional research, just one point assessment was performed prior to diagnostic confirmation. Furthermore, dysgeusia and xerostomia were assessed subjectively, which adds to the study's limitations. More research is needed to confirm the link between SARS CoV-2 infection and oral symptoms following COVID-19 therapy, as well as objective examination of taste and salivary flow in suspected patients.

5. Conclusion

The results of the study suggest that xerostomia and dysgeusia can be used as indicators for identifying suspects of COVID-19 disease while intraoral signs like ulcers need further evaluation. Along with the various clinical manifestations of the COVID-19 disease consideration should also be given to xerostomia and dysgeusia, which will help in early identification and treatment of the suspects of the disease and thus halting its spread.

Funding sources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

None.

Footnotes

IEC No: AIIMS/MG//IEC/2020-21/56 dated 19/09/2020 (All India Institute of Medical Sciences, Mangalagiri)

Contributor Information

Jitendra Chawla, Email: jitendra.dental@aiimsmangalgiri.edu.in.

Navaneeth Y, Email: nav.omfs@aiimsmangalagiri.edu.in.

Satvinder Singh Bakshi, Email: saty.bakshi@gmail.com.

Vinoth Kumar Kalidoss, Email: vinothkk@aiimsmangalagiri.edu.in.

Shikha Yadav, Email: drshikhayadav@gmail.com.

Swapnika Polineni, Email: swapnika.polineni@gmail.com.

Cheranjeevi Jayam, Email: drjayam.dental@aiimsmangalagiri.edu.in.

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