Oral manifestations of COVID-19 in a group of Sri Lankans infected with SARS-CoV-2

INTRODUCTION

COVID-19 is primarily a disease of the respiratory tract, although multiple systemic involvements have been reported occasionally. Main clinical presentations of COVID-19 include sore throat, cough, sneezing, fever, headache, and myalgia. Intriguingly, several investigators have reported numerous orofacial manifestations of SARS-CoV-2 infection including taste and smell disturbances, xerostomia, salivary gland disorders, and mucosal lesions.^[1-8] In an extensive review of patients admitted to hospital, Orilisi et al.^[9] have reported that oral ulcers, cheilitis, and tongue lesions were more common before hospitalization, while perioral pressure ulcers, macroglossia, blisters, and oral candidiasis were more frequent during hospitalization of COVID-19 patients.

These investigators have suggested that initial oral lesions could be related directly to COVID-19, while the latter could be caused by medical devices, treatments, prone position, and immunological impairment.^[8]

It has been already demonstrated that ACE-2 receptors on the oral and salivary gland mucosa attract SARSCoV-2 and facilitate COVID-19 infection of the salivary glands and oral mucosa giving rise to a battery of orofacial manifestations.^[10,11] Orofacial manifestations of COVID-19 may be initial alarming signs that are often presented to the dental healthcare workers and the lesions may create a threat of cross-infection and infection transmission during aerosol generating dental procedures in particular. In addition, the early detection of oral manifestations of COVID-19 by the dental healthcare worker may help facilitate appropriate referral. However, studies that have assessed orofacial manifestations in active COVID-19 patients are hampered due to the risk of infection transmission. In a pioneering study, Natto et al.,^[7] using a convenience sample of 109 COVID-19 patients, have reported that loss of taste was the most common oral manifestation, followed by desquamated gingivitis, coated tongue, and ulceration. Furthermore, Villarroel-Dorrego et al.^[12] have reported that altered taste and a painful/burning mouth were common symptoms among 55 COVID-19 patients in Venezuela. These investigators have suggested that the oral examination may also be useful in confirming the COVID-19 patients.

Even though early detection of such conditions may be valuable in directing the patients for proper medical care, detailed oral examination in COVID-19 patients is limited due to the risk of infection transmission. As a result, studies to explore the orofacial manifestations of COVID-19 and the associated factors are inadequate, especially in south Asian region to date. Hence, the aim of this study was to investigate the orofacial manifestations of COVID-19 using a group of Sri Lankans affected with SARS-CoV-2 during the outbreak in early 2021.

MATERIALS AND METHODS

A descriptive cross-sectional study was conducted using a pretested structured questionnaire which was developed according to the recent literature on orofacial manifestations of COVID-19. Convenience sample of COVID-19 patients (n = 1112) who had been diagnosed with positive PCR or RAT test and treated in an intermediate care center in Penideniya, Peradeniya, Sri Lanka during January–May, 2021, was included as the study population. Questionnaire was administered over the telephone to the participants on the 7^th day following positive PCR or RAT test and the responses were recorded. Ethical clearance for the study was obtained from the Ethics Review Committee of the National Hospital, Kandy, Sri Lanka (NHK/ERC/04/2021) and informed verbal consent was obtained from all the participants in the study before data collection.

RESULTS

A total of 1112 COVID-19 patients (mean age of 34.1 ± 19 years) consented and participated in the study. They included 90 (8%) males and 1022 (92%) females. Out of the total population, there were 16 (1.4%) participants with betel chewing habit. Other demographic data are summarized in [Table 1].

There were 644 (58%) patients with general symptoms and 160 (14.4%) patients having at least one orofacial manifestation of COVID-19. Data regarding the occurrence of general symptoms with regard to COVID-19 (fever, sore throat, coughing, sneezing, headache, myalgia, etc.,) and the numerous orofacial manifestations (anosmia, dysgeusia, xerostomia, oral ulceration, erythema, etc.,) are summarized in [Table 2].

The presence of orofacial manifestations was significantly associated with Sinhalese, married females (Chi-square = 15.9, 19.7, 4.7; P < 0.05). Furthermore, orofacial manifestations were significantly common among patients who had systemic manifestations of COVID-19 (Chi-square = 48.7; P < 0.05) and the absence of betel chewing habit (Chi-square = 16.7; P < 0.05). Specific localized oral lesions were found in 15 patients as indicated in [Table 3].

DISCUSSION

This study has explored the occurrence of orofacial manifestations of COVID-19 in a relatively bigger sample of Sri Lankans affected by SARS-CoV-2. Notably, 92% of the current sample of COVID-19 patients included females, because this intermediate care center was basically reserved for female patients. Considering the average age of these patients, young adults (mean age of 34.1 ± 19 years) were largely affected by COVID-19. Supporting the foregoing data, Purba et al.^[13] have reported that the mean age of COVID-19 affected patients in Indonesia was 35.3 years and 82% of the patients were females. Furthermore, an Iranian study has also revealed a high incidence of COVID-19 infections in the 30–39 and 40–49 year age groups.^[14] Moreover, the young and adult population in USA had experienced more COVID-19 prevalence.^[15] In general, preponderance to COVID-19 among young and adult population may have resulted by their close social interactions probably for academic, occupational, domestic, and recreational purposes and needs confirmation with further investigations.

It is also important to note that the married personnel (64%) were highly affected by COVID-19 in this study. This may be attributed to the fact that married personnel engaged in day to day domestic work and employment that may have created a higher exposures risk to SARS-CoV-2. Further, analysis of the ethnic composition of the patients revealed that majority Sinhalese followed by Tamils and Muslims had COVID-19 denoting the overall ethnic profile of the country [Table 1]. With regard to the diagnosis of patients with COVID-19, majority had been detected by RAT or PCR conducted for contact tracing (62%) rather than on symptoms (22%) or random checking (16%). Therefore, it is likely that the disease had been limited basically to isolated clusters in the society, where rapid transmission had taken place within via close contacts. Above findings may illustrate the importance of social distancing, respiratory etiquette, hand hygiene, and masking in prevention of the disease in the community.^[16]

When the numerous disease manifestations were assessed, 58% of the participants had systemic manifestations, while 14.4% had orofacial manifestations [Table 2]. Intriguingly, orofacial manifestations were commonly experienced by the patients who had systemic manifestations of COVID-19. Therefore, the possibility of having both systemic and orofacial manifestations together was high compared to having either systemic or orofacial manifestations alone. In contrast, Mortazavi et al.^[2] have reported that orofacial manifestations appeared at the asymptomatic early phase of COVID-19. On the other hand, another systematic review has shown prevalence of orofacial manifestations as 33% in COVID-19 patients.^[5] Moreover, in a group of COVID-19 patients in Venezuela, Villarroel-Dorrego et al.^[12] have reported that 40% of the patients had at least one oral manifestation. However, it is important to note that the occurrence of orofacial manifestations of COVID-19 may be underreported, mainly due to the lack of oral examination of patients with suspected and/or confirmed COVID-19. Accordingly, further studies may be useful to demystify conflicting observations regarding the prevalence of orofacial manifestations of COVID-19. In addition, occurrence of orofacial manifestations of COVID-19, in our sample, was significantly associated with Sinhalese, married females. This could be attributable to the fact that the majority in the present study were married Sinhalese females. Nevertheless, it is important to note that morbidity and mortality rates due to COVID-19 have been associated with racial differences in some parts of the world.^[17] Hence, further epidemiological studies are warranted to compare the vulnerability of different communities to COVID-19 in Sri Lanka.

Intriguingly, orofacial manifestations were significantly associated with those who were without betel chewing habit. Besides, it is important to note that betel quid chewing habit may affect deleteriously on the oral soft and hard tissues leading to staining, ulceration, salivary and taste dysfunction, etc.^[18] Accordingly, it could be hypothesized that betel chewing may have masked the subtle changes in the oral cavity induced by the infection of SARS-CoV-2. However, further studies using bigger sample of betel chewers affected with COVID-19 would be helpful to ascertain the above phenomenon.

Leading orofacial manifestations of COVID-19 identified in this study were dysgeusia (11%), anosmia (7.7%), and xerostomia (5.8%). These findings corroborated with the previous observations that the most common oral manifestations of COVID-19 were salivary gland dysfunction, xerostomia, taste and smell alterations, and oral mucosal lesions.^[2] Moreover, in a comprehensive systematic review, Dos Santos et al.^[1] have indicated that gustatory impairment was the frequent oral manifestation of COVID-19, with a prevalence of 45% that included 38% dysgeusia, 35% hypogeusia, and 24% ageusia. Furthermore, Fantozzia et al.,^[19] in a retrospective survey of 326 COVID-19 patients, have reported that the taste dysfunction (59.5%) was the commonest manifestation, followed by xerostomia (45.9%) and olfactory dysfunctions (41.4%). Furthermore, Sheng et al.^[20] in a study that covered a group of Taiwanese have reported that dysosmia and/or dysgeusia were common symptoms particularly in the early stage of COVID-19. Similarly, Natto et al.^[7] in a group of Saudi patients who were symptomatic with COVID-19 have reported that loss of taste (43.4%) was the most prevalent specific oral manifestation. According to Villaroel-Dorrego et al.^[12] who have assessed 55 COVID-19 patients in Venezuela, the taste disturbance rate was 60%. Biadsee et al.,^[21] in a web-based questionnaire study using 140 COVID-19 patients, have reported that xerostomia was prevalent in 56% of the patients. Furthermore, in a Sri Lankan study that assessed 100 patients with COVID-19, it has been revealed that the prevalence of altered smell and taste as well as xerostomia amounted nearly up to 70%.^[8] However, the prevalence rate of dysgeusia, anosmia, as well as xerostomia in the present study is relatively lower than the previous reports and further studies would be expedient to confirm their prevalence in Sri Lankan COVID-19 patients.

Huang et al.,^[10] using COVID-19 autopsies, have showed that the cells of the oral epithelium, taste buds, and salivary glands express ACE2 and TMPRSS2 that attract SARS-CoV-2. Further, in an extensive review, Okadaa et al.^[11] have shown that ACE2, TMPRSS2, and furin molecules in the oral mucosa and the salivary glands facilitate entry of SARS-CoV-2, leading to inflammation and cellular damage. Collectively, these investigators have confirmed that SARS-CoV-2 infected salivary glands and oral mucosa produced malfunction of salivary glands and the taste buds. Overall, it is reasonable to assume that SARS-CoV-2 infection of the salivary glands and the oral mucosa may lead to xerostomia as well as dysgeusia. Furthermore, olfactory dysfunction may indirectly alter the taste sensations physiologically.^[22] Accordingly, infection of the olfactory epithelium by SARS-CoV-2 may bring about anosmia secondarily altering the taste sensation in COVID-19 patients, a phenomenon which warrants further investigation.

With regard to current study population, the most common specific lesions appeared on the oral mucosa included appearance of whitish plaque over the tongue, palate, lip and the angle of the mouth followed by burning sensation of the tongue. There were two patients who had ulceration and bleeding from the tongue and one person each presented with erythema of the hard palate and the angle of the mouth [Table 3]. In a comprehensive systematic review, Dos Santos et al.^[1] have stated that oral mucosal lesions in COVID-19 patients included white and erythematous plaques, irregular ulcers, small blisters, petechiae, and desquamative gingivitis affecting tongue, palate, lips, gingiva, and buccal mucosa. In another study, it has been reported that the most common oral lesion in COVID-19 patients was oral ulceration followed by xerostomia, dysgeusia, gingival inflammation, erythema, and oral ulceration.^[23] Although our findings substantiate the above, further studies using clinical examination of bigger patient samples would be beneficial to confirm exact prevalence of mucosal lesions due to COVID-19.

CONCLUSION

Foregoing findings demonstrate that COVID-19 produces orofacial manifestations such as dysgeusia, anosmia, xerostomia, and mucosal lesions. Dental healthcare workers should be able to detect such COVID-19-related orofacial manifestations for the first time and refer patients for appropriate medical care. Inquiry about orofacial lesions from COVID-19 patients may also be vital in proper management. Finally, oral hygiene must be promoted in COVID-19 patients to avert any further clinical complications.