Effect of COVID-19 on oral mucosa: Literature review

Oral manifestations of COVID-19

COVID-19 has impacted every aspect of society and is currently the focus of attention in both developed and developing countries.^[16,17] When WHO declared COVID-19 as a pandemic disease in March 2020, the research related to it surged, and so did the publications. A variety of symptoms related to SARS-CoV-2 infection have been identified in the oral cavity. These symptoms include taste loss, dry mouth,^[15] and oral cavity lesions such as ulcers resembling aphthous, Koplik’s and Nagayama’s spot, papulovesicular or maculopapular lesions, red/white patches, edematous gingiva, lip swelling, and petechiae. There may be involvement of both non-keratinized (labial and buccal mucosa) and keratinized (Hard palate, Gingiva, and Dorsum of tongue) mucosa.^[13]

Various publications have mentioned that the SARS-CoV-2 receptor-binding domain has a strong affinity for ACE2-functional receptors. The lining mucosa of the nose, lung pharynx, oral mucosa, salivary glands, and several human organ systems are all ACE2-rich, which makes them both susceptible to viral damage and a portal for viral entry into the body. As a result, three categories could be used to discuss the various oral manifestations of COVID-19 that have been documented in the literature and reviewed here.^[10]

• Category 1 – Due to direct link to SARS-CoV2 infection [Table 1]

• Category 2 – Due to coinfection secondary to SARSCOV-2 therapy [Table 2]

• Category 3 – Due to immunologic abnormalities in hospitalized patients [Table 3].

Oral manifestation due to direct link to SARS-COV-2 infection

Xerostomia: The most prevalent cause of decreased saliva output was infection with SARS-CoV-2. In addition to their main complaint of dry mouth, patients with xerostomia often reported experiencing other symptoms such as dysgeusia, angular stomatitis, and a burning sensation in the oral cavity.^[16] In the ductal epithelial cells and acinar of the salivary glands, Fakhruddin et al. demonstrated the abundant expression of ACE2 and transmembrane protease serine receptors for SARSCOV-2, which results in a reduction in salivary production and oral cavity infections.^[10] In the studies conducted by Tuter et al. (2022),^[8] Fakhruddin et al. (2022),^[10] Fantoozi et al.^[18] Fernandes et al.^[19] the frequency of dry mouth was found to be 47.6%, 69.85, 45.6%, and 53%. Throughout all these studies, xerostomia was the most common oral symptom among COVID-19 patients, and it did not statistically differ between patients in different age groups.

Taste buds/tongue impairment: Studies conducted on the prevalence of tongue impairment by different authors; Sinjari et al.,^[20] Fantoozi et al.,^[18] Vallarroel Doreggo et al.,^[21] found 25%, 87%, 60% of prevalence, respectively. According to almost all published studies, research indicates that the different types of taste disorders, which includes ageusia, hypogeusia, and dysgeusia, is most often caused by increased proliferation and hypertrophy of the tongue’s filiform papillae, which results in a metallic taste, in addition to a lack of desquamation.^[22]

Burning mouth syndrome: According to Fakhruddin et al. (2022), the majority of individuals with altered taste disorder and dry mouth report a burning mouth sensation. ^[10] However, the burning mouth feeling is a fairly general disease that can be linked to a wide range of other conditions, such as mental health issues, mineral or vitamin deficiencies, diabetes, candidal infections, and various medications. Few more studies conducted by authors Nuno-Gonzalez et al.,^[23] El-Kady et al.,^[24] El Tantawi et al.,^[25] Mohammad et al.,^[26], and Al- Magsoosi et al.^[27] show the prevalence of burning mouth syndrome in 5.3%, 22.4%, 13.1%, 22,5%, and 28.5% of cases, respectively.

Ulcerative lesion: Among all patients examined for COVID-19, oral ulcers were the most prevalent lesion.^[10] The common source of all the diseases is thought to be host’s defense system response to viral antigenic components of the mucosal epithelium, or abnormalities in the oral mucosa’s superficial epithelial barrier caused by viral invasion.^[10] Gheolone et al.,^[28] Abubakr et al.,^[29] Tuter et al.,^[8] Fernandes et al.,^[19] and observed ulcers in 12%, 20.4%, 14.5%, 54%, of cases, respectively.^[8,21]

Brandao et al.^[30] Chaux-Bodard et al.,^[31] and Ciccarese and Demirbas et al.^[32] have described different types of an ulcer like herpetiform, aphthous-like ulcers, vesiculobullous, and maculopapular in COVID-19 patients.

Angina bullosa: According to Fakhruddin et al. (2022), angina bullosa is an inflammatory response caused by SARS-CoV-2 and is considered to be a symptom of thrombus formation and subsequent vascular endothelial failure.^[10] According to Favia et al.^[33] and AL- Mastoogi et al.,^[27], the prevelance of angina bullosa was 8.42% and 14.5 % respectively reported in COVID-19 investigations.

Petechiae: Iranmanesh et al. (2021)^[13] stated that the palate, oropharynx mucosa, and lower lip all had petechiae. One possible cause of this could be COVID-19-related thrombocytopenia.^[10] Patients with petechiae had a shorter latency period.^[13] Some authors as Binmadi et al.,^[34] and Fernandes et al.^[19] observed 11%, and 7.4% of prevalence, respectively.

Oral manifestation of COVID-19 due to co-infection secondary to SARS-COV-2

Fungal infections: Even after the COVID-19 signs and symptoms have subsided, opportunistic fungal infections may result from generalized immunosuppression.[10] Among COVID-19 patients, the most prevalent fungal infections found are candidiasis, mucormycosis, and aspergillosis.

Candidiasis: Fakhruddin et al. have stated that Candida albicans is the most prevalent causative yeast for mucosal candidiasis, which is very likely to occur in COVID-19 patients.^[10]

In diabetic patients receiving SARS-CoV-2 treatment, there has been a notable increase in the incidence of angioinvasive maxillofacial fungal infections, which has been linked to corticosteroid medication.^[14] Sharma et al. (2022) conducted a study on 18 cases of COVID-19 patients and observed 16 patients with mucormycosis, followed by one patient with aspergillosis and one patient with mixed fungal infection.^[14] Other studies by Selehi et al.^[35] observed a 70.7% high risk of C. albicans. Oral pseudomembranous candidiasis was another common fungal lesion observed in studies conducted by Bardellini et al.^[36] and Binamdi et al.,^[34] they found prevalence in 7.4%, and 27% of cases, respectively.

Mucormycosis: Mucormycosis, often referred to as “black fungus disease,” is a somewhat frequent presentation that has mostly been recorded from the Indian subcontinent. Following recovery from COVID-19, it may manifest as mouth ulcerations.^[10]

Aspergillosis: Pulmonary aspergillosis is the third most prevalent fungal illness found in COVID-19 patients.^[10]

Mucositis: Mucositis due to thrombotic vasculopathy, vasculitis, or virus-related hypersensitivity is observed as secondary lesions after COVID-19 infection.^[13] Almost 3.9% of similar cases were observed in the study carried by Nuno-Gonzalez et al. (2021).^[23]

Oral manifestation due to immunologic abnormalities in hospitalized patients

Necrotizing–ulcerative gingivitis (NUG): In study conducted by Iranmanesh et al. and Erbas et al. in the year 2021 and 2022, the patients examined for COVID-19 presented with NUG in the oral cavity, the lesions were edematous, unpleasant, and diffusely erythematous in necrotized interpapillary areas.^[13,37]

Gingivitis: According to Fernandes et al. 2023, the serious consequences of COVID-19 cause a lack of proper oral hygiene measures, which contribute to the development of gingivitis. Gingivitis emphasizes the necessity of improving oral health awareness and maintaining appropriate oral hygiene practices.^[19] The authors Anand et al. in^[38] and Fernandes et al.^[19] show a prevalence of cases of gingivitis in 93.7% and 22.7% of cases, respectively.

Periodontal health/periodontitis: Literature of Frenandes et al.^[19] has described a severe and rapidly progressing disease that affects free, attached gingivae or the alveolar mucosa, causing ulceration, discomfort, necrosis, and bleeding.^[19] The illness can develop as a consequence of chronic gingivitis in debilitated individuals or immunocompromised patients. In general, the condition was observed in several critically ill COVID-19 patients who have poor oral hygiene.^[10] Marouf et al.,^[40] Binmadi et al.,^[34] and Anand et al.^[38] observed prevalence of cases of periodontitis in 44%, 4%, and 49.4% of case, respectively.

Halitosis: Halitosis is an expressing state for a range of systemic illnesses, including respiratory, otolaryngologic, and gastrointestinal pathologies, that may affect salivary features and tongue dorsum susceptibility to host anaerobic microbes. According to the study of Riad et al.,^[41] the COVID-19 has posed a significant threat to halitosis, with a small number of confirmed individuals presenting with halitosis.^[41] Abukhar et al.,^[29] Bullet et al.,^[42] Muthyan^[43] observed 10.5 %, 21%, 2% cases of halitosis respectively.

Melkersson-Rosenthal syndrome: Melkersson-Rosenthal syndrome is characterized by hyperemic lower lip with firm edema spreading to the jaw, right facial paralysis, and fissured tongue. It was determined that activated mast cells, which produce cytokines in the lungs, may play a substantial role in the pathogenesis of COVID-19 infection and may be a potential etiological cause for this presentation.^[14]

Tongue coating: Literature suggested that abnormal tongue-coating patterns were seen in COVID-19 patients.^[44] These coating patterns are linked to inflammatory responses and can provide insight into the course of the illness. The most often reported subjective signs of lingual involvement were red tongue, yellow, greasy, white coating, greyish-black coating, spots, spikes, and tooth-marked tongue. It is interesting to note that individuals with fewer cases of COVID-19 had tongues that were thinner and lighter in color. On the other hand, thicker coatings, more painful tongues, and purple tongues were seen in patients with more severe instances.^[22]

During the COVID-19 pandemic, tongue villosa nigra, or BHT, is commonly observed in individuals with extrapulmonary function.^[22] The prevalence of tongue coating observed in the study conducted by Naser et al.,^[45] Eduardo et al.,^[46] Fernandes et al.,^[19] and Natto et al.^[47] showed tongue coating in 4.7%, 3%, 7.4%, and 7.3%, respectively.

Angular cheilitis: Angular cheilitis is an inflammatory condition that appears as approximately triangular lesions at the labial commissures. Its typical symptoms are red, edematous, and frequently painful patches of skin; mild instances may just exhibit some reddish erythema with neighboring lips that are either normal or chapped.^[48]