A multi-country study on the impact of sex and age on oral features of COVID-19 infection in adolescents and young adults

Oral lesions are associated with several systemic or local infections caused by micro-organisms. These include primary and secondary viral pathological lesions associated with oral infective diseases and dysplastic-neoplastic transformations [1]. These oral lesions cause distress, physical and psychological disabilities, as well as functional limitation [2].

COVID-19 infection is associated with oral lesions such as gustatory impairment either due to the effect of the virus on oral tissues or as secondary manifestations resulting from it [3]. Other identified oral lesions include Aphthous-like ulcer, erythema, and lichen planus [4].

The oral lesions associated with COVID-19 infection have been reported in adults. There are, however, differences in the clinical manifestations of COVID-19 in children compared to adults [5, 6] which may imply differences in the presence of oral lesions associated with COVID-19 infection by age. However, there is little known about the oral features of COVID-19 among adolescents and young adults (AYA). Also, there is limited known about sex differences in the oral features of COVID-19 infection among AYA. Yet, identifying sex and age differences in the oral features of COVID-19 is important for characterising the lesions, and enabling health care providers to improve the oral health management for AYA. Therefore, the aim of the present study was to assess the associations between some oral conditions and COVID-19 infection in AYA; and to investigate sex and age differences in these associations. The null hypothesis of the study was that no oral conditions would be associated with COVID-19 infection; and age and sex would not modify this association.

Complete data were available for 7164 participants from 43 countries. Table 1 shows that 4109 (57.4%) participants were females, 5342 (74.6%) were 18–23 years old, 4079 (56.9%) were university educated and more than 40% of participants had mothers or fathers with university or higher education. Also, 925 (12.9%) reported having medical problems and 540 (7.5%) were infected with COVID-19.

Table 2 shows that 4140 (57.8%) participants reported no oral conditions. The most frequently reported oral conditions were gingival inflammation (10.7%) and dry mouth (7.5%). Change in taste was reported by 238 (3.3%) participants.

A significantly higher percentage of participants with COVID-19 than those who had no COVID-19 infection reported having dry mouth (10.6% vs 7.3%, p = 0.008), change in taste (11.1% vs 2.7%, p < 0.001) and oral ulcers (2.4% vs 1.1%, p = 0.01). A significantly higher percentage of participants with no history of COVID-19 infection than those with an infection reported having no oral conditions during the pandemic (58.6% vs 48.0%, p < 0.001).

Table 3 shows the results of the multilevel binary logistic regression analysis for the association between the presence of oral conditions and COVID-19 infection reported by participants. COVID-19 infection was associated with significantly higher odds of the presence of dry mouth (AOR = 1.31, p = 0.002) and change in taste (AOR = 4.11, p < 0.001).

Age significantly modified the association between COVID-19 infection and the presence of dry mouth: AYA 18 to 23-year-olds had significantly lower odds of having dry mouth associated with COVID-19 infection than 15 to17-year-olds and 11 to14-years-olds (AOR = 1.31 vs 1.64 and 1.48, p = 0.02). Age also significantly modified the association between change in taste and COVID-19 infection: 15–17-year-olds had higher odds of having a change in taste associated with COVID-19 infection than 18–23-year-olds and 11–14-year-olds (AOR = 5.79 vs 2.70 and 2.28; p < 0.001).

Sex significantly modified the association between the presence of gingival inflammation and COVID-19 infection: males had significantly higher odds of the association than females (AOR = 1.30 vs 1.09; p = 0.04). Sex also modified the association between dry mouth and COVID-19 infection: males had higher odds of having an association than females (AOR = 1.42 vs 1.25; p = 0.02). In addition, sex modified the association between change in taste and COVID-19 infection: females had higher odds of this association than males (AOR = 4.92 vs 2.46; p < 0.001).

The findings showed that about 4 in 10 AYA reported oral conditions during the pandemic with change in taste, dry mouth and oral ulcers positively associated with COVID-19 infection. The associations of COVID-19 infection with dry mouth and change in taste were modified by age: there was a stronger association between COVID-19 infection, dry mouth and change in taste among 15–17-year-old participants than among other age groups. Sex also modified the associations of COVID-19 infection with dry mouth and change in taste: males had higher odds for having dry mouth than females, while females had higher odds of having a change in taste than males. The null hypothesis of the study was, therefore, not supported.

One of the strengths of the study was that we provided information on the possible oral features of COVID-19 infection in AYA aged 11 to 23 years; and identified how sex and age modified these associations. Also, the study recruited a large sample of participants from countries representing various income-levels and regions thereby increasing the generalizability and applicability of findings to various settings. The study, however, has some limitations. The oral conditions were self-reported thereby introducing subjectivity to the reporting with the risk of under-estimation of lesions like gingival inflammation and dry mouth. Although a clinical examination might be considered more objective, it was not possible to conduct clinical assessment of study participants because of the restrictions with contacts during the pandemic. This was the case in most of studies assessing oral lesions during the COVID-19 pandemic [3]. However, a study conducted to assess self-report for disease surveillance reported a satisfactory outcomes for patent’s’ self-reporting their disease category [13]. We, additionally, focused on oral conditions that patients are likely able to self-report thereby reducing assessment bias. The data was based on a convenience sample driven by snowball sampling where participants refer the survey link to people they know because data collection was restricted to online methods during the pandemic. These non-probability samples introduce some bias as only participants who have a smartphone and who can access the internet could participate in the study. Such participants are not similar to the general population in each country which may affect the generalizability of findings. In addition, the study is cross sectional and cannot, therefore, prove causality.

The association between COVID-19 infection and change in taste and dry mouth had been reported and explained in previous studies [14‐16]. However, none of them discussed these changes in AYA. Taste disorders, oral ulcerations, desquamative gingivitis, candidiasis [17‐19], halitosis, erythema, and spontaneous bleeding from the gingiva [19] were also associated with COVID-19 infection. In a symptomatic paediatric cohort, taste alterations were also reported [20]. These oral conditions may be the side effects of SARS-CoV-2 infection, or may be the sequel to super-infections, immuno-compromise, or complications of medications used to manage COVID-19 infection [21]. Psychological stress, a complication of the COVID-19 pandemic [22, 23], and poor oral hygiene during the pandemic might also play a part in the manifestation of gingival inflammation, dry mouth, and ulcers. Some lesions may be attributed to ACE2 receptor of SARS-CoV-2 found in the mucosa acting as a gateway to COVID-19 infection [24].

The association between COVID-19 infection and gingival inflammation and dry mouth was stronger in males than females in the present study. While a male predilection was noticed in the current study, previous research showed that these symptoms were more frequent in females than males [5, 25‐27]. It is important to note that these studies were all conducted on adults. This emphasizes the importance of the present study finding suggesting gender differences in younger age groups. Further studies including AYA are needed to confirm this relationship. On the other hand, females showed a stronger association between COVID-19 infection and taste changes like a prior study by Galmiche, et al. [28] which reported a higher alteration in taste among females compared to males. Taste perception can vary by sex, probably because females have more fungiform papillae and taste buds than males [29].

In the present study, COVID-19 infection had the strongest association with altered taste in 15–17-year-olds and the oldest age group of 18–23-year-old showed the weakest association between COVID-19 infection and reporting dry mouth. Direct comparison with previous studies is difficult because these studies were either case-reports or were conducted in adults [27, 30]. However, older children were reported to be more able to identify smells and tastes than younger children [31] and thus, more able to detect loss of taste than younger children. Further research is needed to explain the age-related differences in AYA groups.

Participants who had COVID-19 infection were more likely to report change in taste, dry mouth and oral ulcers. Sex and age moderated the associations between COVID-19 infection, dry mouth and change in taste in AYA. These findings may be useful for screening for COVID-19 infection among AYA.