# Oral Lesions in Pediatric Subjects: SARS-CoV-2 Infection and COVID-19 Vaccination
## 4 Discussion
### Oral Lesions Pediatric Subjects Following COVID-19 Vaccination
The primary oral lesions described were erosive-ulcerative type (40%), with herpes-form (50%) and unspecified (50%) patterns, followed by macule and petechiae (20%). The failure to detect red and white plaques, as well as vesicles and bullae, may be related to the fact that these lesions are asymptomatic and, thus, could be underacknowledged by the family members of pediatric subjects. Moreover, it may be supposed that erosions and ulcers may be the most prevalent. Along with the primary oral lesions, pseudomembranes and crusts, consistent with the evolution of the above erosive-ulcerative lesions, were also described in the remaining 40% of cases. The definitive diagnoses in the two cases reported were [PERSON]'s disease [24] and Erythema Multiforme [25]. Therefore, it may be speculated that clinicians' attention may have been primarily focused on systemic involvement rather than oral phenomenology, which was not characterized adequately in similar cases described in the literature. However, this finding differs from the adult population with oral ADRs, primarily belonging to lichenoid reactions and Oral Lichen Planus [2; 48; 50; 51], followed by Stevens-Johnson syndrome and Erythema Multiforme [25; 42; 46]. It may be speculated that lichenoid reactions and Oral Lichen Planus show a predilection for older subjects, and, thus, have not been found, to date, among oral ADRs to COVID-19 vaccines in the study population. Erythema Multiforme, instead, was also commonly diagnosed in pediatric SARS-CoV-2 positive subjects, and is known to be diagnosed with previous Herpes Simplex virus type-1 and Mycoplasma Pneumonia infections, occurring, in turn, with a higher frequency in adolescents and young adults [52]. Considering oral mucosal lesions potentially related to viral infection and vaccine administration together, erosive-ulcerative lesions (10%) and maculae and petechiae (13%) were the most frequent oral primary lesions, and no case was diagnosed with white or red plaques, nor with vesicles and bullae. Other lesions, accounting for the majority of the total diagnosis (77%), were very heterogeneous and also included normal variations, such as the geographic tongue [31]. In any case, no increase in the detection of oral lesionshas been highlighted, to date, as concomitant to the SARS-CoV-2 pandemic, in pediatric subjects. Conversely, a higher identification rate of skin lesions, mainly comprising pseudo-chilblains at the acral regions, which are thought to be among the most peculiar cutaneous manifestations in pediatric SARS-CoV-2 infection, Erythema multiforme, and various types of rashes and urticaria, have been registered [53]. No cyto/histological investigations were performed in any of the studies included in the present systematic review. However, insights into the microscopic characteristics of oral lesions in pediatric subjects may help to identify the pathogenic mechanisms involved in the onset and progression of such lesions. In addition, considering that histopathological findings have been described for adult subjects [54], a comparison between them may indirectly highlight any prevalent pathogenic mechanisms [55], potentially resulting from the different ages and related immune capacity [55]. The study's main limitations may rely on the fact that besides the very inclusive eligibility criteria and the timeliness of the topic, very few studies were retrieved from the literature. In addition, reported findings were very heterogeneous and incomplete, likely because oral outcomes were often not the focus of the studies included in this systematic review; therefore, a meta-analysis could not be conducted. However, to the best of our knowledge, the present systematic review may be considered the first that qualitatively analyzed data from pediatric subjects on primary oral lesions potentially associated with SARS-CoV-2 infection, estimated the degree of association and grading of primary oral lesions based on COVID-19 forms, and followed COVID-19 vaccines in relation to cases and vaccine type and administered doses.