In this study, xerostomia and dysgeusia/ageusia were the most frequent oral manifestations in symptomatic participants regardless of the molecular confirmation of COVID-19. These results weresimilar to another study conducted with 128 non-hospitalized patients with COVID-19 confirmed by rRT-PCR, where 56% of patients reported xerostomia as the most frequent oral manifestation, followed by gustatory dysfunction (32.8%)[16].
Gingivitis and halitosis were more frequent in the rRT-PCR-positive group than in the RT-PCR-negative group. Both oral findings could be associated with a lack of oral hygiene, stress, or immunosuppression, which might be some of the most important predisposing factors for the onset of oral lesions in COVID-19 [12]. Gingivitis is a mild periodontal disease characterized by inflammation of the gums and is mainly caused by poor oral hygiene[17]. Periodontal disease is caused by poor oral hygiene, which results in bacteria in dental plaque. The presence of these bacteria causes a local inflammatory reaction and the emergence of neutrophils and other inflammation-promoting cells that receive the mediation of proinflammatory cytokines [18]. Furthermore, evidence suggests that the worsening of SARS-CoV-2 infection in the lung region may be caused by the aspiration of periodontal pathogens, increasing the secretion of inflammatory cytokines such as IL-6 [19]. Our results are similar to those of Anand et al., where periodontitis was more frequent among COVID-19 patients[20].
In the symptomatic RT-PCR-negative group, mouth ulcers were self-reported in 12 participants (14.6%) but observed in only three participants (3.7%) during the oral examination. In contrast, only five participants (10.0%) reported mouth ulcers in the RT-PCR-positive group, with none presenting with such lesions during the clinical oral examination. According to a Spanish study [11], vesicular eruptions (1.6%) were observed in a minority of patients and appeared within the first few days of illness onset. This finding may suggest that vesicular eruptions in the Spanish study and mouth ulcers in our study could be more frequent in the early prodromal phase of the disease.
Glossitis was observed in both groups in our study, with similar relative frequencies. A Spanish study of 666 hospitalized COVID-19 patients presented several oral cavity findings, including transient lingual papillitis (11.5%), aphthous stomatitis (6.9%), and glossitis with lateral indentations (6.6%) [11].They suggested that these alterations could also be due to certain procedures in hospitalized patients, including ventilation masks. Papillitis was not observed in the present study, however, isolated glossitis and glossitis with lateral indentations were associated with tongue coating.
Glossitis with lateral indentations (teeth marks on the sides) was described as tongue depapillation with bilateral atrophy of the tongue's surface located in the lateral sides, recently coined as “COVID tongue”. Both oral manifestations are related to a particular state of immunosuppression, and stress may play an essential role in the appearance of these oral conditions[12, 21].
Tongue coating (yellow color) was found in four participants (7.4%) in the RT-PCR-positive group and only two participants (2.4%) in the symptomatic negative group, with no statistically significant difference between the groups. In addition, tongue coating and glossitis with indentations appeared together in some patients and were observed in both groups. According to a retrospective cross-sectional study of tongue features in 1043 patients with COVID-19[22], with disease progression, the proportion of critically ill patients with yellow tongue coating increased to 62.5%. The authors agreed that fever and infection might cause it to turn yellow. Furthermore, the degree of yellow coating was positively correlated with the degree of lung infection and disease severity. In addition, tongue color change could be attributed to difficulties in complying with meticulous oral hygiene measures, as the severity of the disease increases and deteriorates[23].
Petechiae were found in the RT-PCR-positive group (n = 4; 7.4%) and the symptomatic negative group (n = 3; 3.7%). These findings are consistent with those of previous studies that reported petechiae on the palate, lower lip, and oropharyngeal mucosa during COVID-19 [24, 25]. These authors suggested that the oral lesions were associated with COVID-19. In our study, petechiae were found in the soft palate of seven patients. However, the direct effect of SARS-COV-2 on these lesions remains uncertain because other conditions may be related to these findings besides viral infection, such as adverse drug reactions [24].
The findings of oral manifestations in both groups were relatively similar, although it was not possible to detect SARS-CoV-2 using rRT-PCR in all participants. Recent studies suggest that RT-PCR for SARS-CoV-2 detection should be performed between the third and seventh days of symptom onset to reduce false negative results [26]. Although the participants in our study performed the RT-PCR test an average of 4.68 days after the onset of signs and symptoms, the range was from one to 16 days, leading to potential false negative results. Another explanation for false-negative results is the sensitivity (86%) and specificity (96%) of the PCR test used for diagnosis. Therefore, a second sample collection is recommended when the first evaluation is negative, to improve the probability of confirming the diagnosis using this molecular technique[27].
Our study has limitations that cannot be generalized to all COVID-19 patients. First, we evaluated only patients with mild-to-moderate disease and not hospitalized patients with more severe forms of COVID-19. Second, we did not analyze the use of medications to treat pre-existing diseases, which may have influenced tongue findings and xerostomia. Third, as previously discussed here, a second sample was not systematically collected from all symptomatic patients with negative RT-PCR results.
COVID-19 has a high infectivity rate, mainly because of its spread through respiratory droplets. In addition to studying the role of saliva in the transmission of the virus and as an alternative fluid for diagnosis, one must carefully ensure the identification of saliva quality and presence of xerostomia. A thorough oral clinical examination can indicate the presence of oral manifestations related to COVID-19, and thus establish immediate measures to reduce the transmission and pathogenicity of SARS-CoV-2.
In conclusion, a high prevalence of oral manifestations was observed in symptomatic patients with suspected or confirmedCOVID-19, highlighting the importance of routine oral examinations by dentists as part of the multidisciplinary care of COVID-19 patients.