The appearance of oral manifestations in children infected with COVID-19: A critical review of the literature

Michelle Antonette Brown¹, Xania Dawes ¹, Arvind Rajendra Santosh¹

¹School of Dentistry, Faculty of Medical Sciences, The University of the West Indies, Mona, Jamaica

Corresponding author:
Michelle Antonette Brown
School of Dentistry, Faculty of Medical Sciences, The University of the West Indies, Mona, Jamaica
email: [email protected]

DOAJ: 6ac152b62d8846209ef6aefbffbb0197
DOI: https://doi.org/10.48107/CMJ.2023.09.002
Published Online: January 8, 2024

Copyright: This is an open-access article under the terms of the Creative Commons Attribution License which permits use, distribution, and reproduction in any medium, provided the original work is properly cited.

©2023 The Authors. Caribbean Medical Journal published by Trinidad & Tobago Medical Association

ABSTRACT

Objective
The aim of this narrative review of the literature is to summarize the evidence on the prevalence of oral manifestations and to ascertain at what point in time oral manifestations present in children infected with SARS-CoV-2.

Method
Databases PUBMED, Google Scholar and Ebsco were used. The search terms: COVID 19, oral manifestations and child, along with age filters were applied to generate the articles published between 2020-2021.The abstracts of the articles were first read and then those articles that were relevant were evaluated in detail.

Results
Hyperaemic pharynx and dysgeusia were prevalent in children with COVID-19 disease while edematous and erythematous lips and strawberry tongue were frequently seen in patients diagnosed with multisytem inflammatory syndrome in children. In some sources the onset of oral manifestations was unclear resulting in inconclusive evidence.

Conclusion
Oral manifestations are commonly seen amongst the earliest manifestations of COVID-19, and may happen prior to presenting other symptoms, or up to a week after other manifestations of the disease. The appearance of oral manifestations in children with COVID -19 like symptoms may be an indicator of disease severity and the likelihood that disease progression could potentially be more severe and have more detrimental outcomes.

BACKGROUND
The novel coronavirus disease (COVID-19) is less prevalent in children than in adults.¹ The lower prevalence in this population has been attributed to the lessened expression of angiotensin-converting enzyme-2 (ACE 2)^2,3, and the presence of different viruses that possibly compete with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)¹.  In addition to low infectivity in children and adolescents, this population experiences less severe symptoms, shorter course of disease and a good prognosis, when compared to adults⁴.  It should be noted that this lower prevalence could be underestimated due to the common asymptomatic nature of the disease in children which could lead to less testing in this population.¹

Multisystem inflammatory syndrome in children (MIS-C) is defined as presenting a high fever, evidence of C-reactive protein ≥3.0 mg/dL (30 mg/L), new onset manifestation in at least two of the following: cardiac, mucotaneous, shock, gastrointestinal and haematologic involvement, in addition to the detection of SARS-CoV-2.⁵There are notable similarities between MIS-C and Kawasaki disease, in which patients present systemic vasculitis.⁶ Findings from a retrospective review study of 47 pediatric patients, conducted in a hospital setting have suggested that oral and oropharyngeal manifestations with COVID-19, could potentially be early indicators of (MIS-C) and were significantly associated with other diagnostic symptoms of MIS-C such as systemic rash and conjunctivitis⁷, however little is known about how soon the oral manifestations present in children. Therefore, the aim of this narrative review was firstly to summarize the oral manifestations seen in children and secondarily to ascertain when oral manifestations present in children infected with SARS-CoV-2.

METHODOLOGY
For this narrative review of the literature, articles were retrieved from PubMed using the MESH terms COVID-19, COVID 19, oral manifestations and the filters: free full text, adolescents: 13-18, child: birth -18 years, child: 6-12 years were applied. The abstracts were all read and those articles which were relevant to the aim of this review were read in detail. The references of the selected articles were checked to find more relevant articles. Google Scholar and EBSCO were also checked for relevant articles using the search terms COVID 19, oral manifestations and child. Where articles were not freely available, the authors were contacted, and requests were made. Only articles in the English language were included in this review and were published between the years 2020 and 2021. The types of articles included were case reports, case series, cross-sectional, cohort and review studies.

RESULTS
The literature search identified 19 relevant articles. Table 1 shows the summary of the prevalence findings in children with COVID-19 and those diagnosed with MIS-C.

Table 1. Summary of prevalence findings of oral manifestations in children with COVID-19 disease.

Prevalence of oral manifestations in children with COVID-19 disease
In a retrospective study including 27 children aged between 3 months to 14 years old, the following oral manifestations were noted: oral pseudomembranous candidiasis (7.4%, n=2), geographic tongue (3.7%, n=1), coated tongue (7.4%, n=2), hyperaemic pharynx (37%, n=10) and taste alteration (11.1%, n=3).⁸

Prevalence of oral manifestations in patients diagnosed with MIS-C
A retrospective study, showed that edematous and erythematous lips (48.9%, n=23) and strawberry tongue (10.6%, n=5) were seen in 47 children who were diagnosed with MIS-C. Other oral manifestations seen in this population that were considered to be less prevalent were sores, mouth pain, oropharyngeal erythema, smile asymmetry and tongue deviation.⁷

In a systematic review that included 662 children with MIS-C, it was found that 4.7%(n=31) had tongue swelling and 51%(n=343) presented with cheilitis.⁹

Amongst 84 patients with MIS-C, red, swollen lips (27.3%) and other unspecified changes in the mouth (19%) were reported in a systematic review.¹⁰

Changes in the oral mucosa, dry and red lips were classified as unspecified oral manifestations (n=185) in a review study were seen in 25-87% of the children with MIS-C.¹¹

A case series including 58 children with MIS-C also reported mucous membrane changes and red, cracked lips in 25% (n=11).¹²

One cohort study compared MIS-C (n=19) and children diagnosed with COVID-19, and found that in the MIS-C group, 21% (n=4) presented fissured lips and 11% (n=2) presented tongue papillitis while the COVID-19 group presented 8% (n=1) fissured lips.¹³

Zaheer et. al 2022 ¹⁴, affirms that the oral lesions seen in the studies ^{9,10, 11,12,13} involved the lips and tongue. The most frequently reported symptoms in these cases were cheilitis, tongue swelling and dry and red mucosal membranes.

Length of time from onset of COVID-19 to the appearance of oral manifestations.
Table 2 shows summary of studies of the timing of oral manifestations relative to other symptoms in children with COVID-19 disease. Oral manifestations such as vesicles and erosions on the anterior tongue, lips and buccal mucosa were noted in a 9-year-old female who tested positive for SARS-COV-2.^15,16  These oral manifestations preceded by 3 days other common symptoms associated with COVID-19 such as dry cough, somnolence, tachypnea and hypoxia.

A 15-year-old male, presented with dysgeusia described as a transient metallic taste when eating that improved after 12 days.² Of note, this oral manifestation began 3 days prior to the manifestation of ear, nose and throat (ENT) symptoms (sore throat, runny nose and nasal congestion) as such was considered as a sentinel symptom.²

Three SARS -CoV-2 positive neonates (2 males and a female) admitted to the hospital, oral candidiasis was found to be present in each neonate. Two of the neonates were asymptomatic and only one experienced COVID-19 related symptoms such as coughing, lethargy and fever. It was unclear at what point the oral candidiasis developed in each child. The relationship between antibiotics and oral candidiasis is well known, however this was ruled out as the possible cause, as only the symptomatic neonate was administered antibiotics and this was after the patient presented the oral candidiasis.¹⁷

In a retrospective study in which the mean age of COVID-19 infected patients was 4 years old (4,2 + 1,7), it was self-reported that geographic tongue appeared concomitantly with elevated fever.⁸

A two- year-old female infected with COVID-19, developed a localized gingival inflammation between the right maxillary incisor and canine the same day she experienced other symptoms such as a fever, nausea and vomiting. A week later several white lesions appeared on the labial mucosa along with desquamation of the epithelium and was otherwise asymptomatic.¹⁸

A 6 -year -old male who was initially asymptomatic, notwithstanding loss of appetite and transient anosmia 2 weeks prior to hospitalization, presented with severe erythema multiforme which included, substantial labial crusting, gingival erosions and a target lesion on the face. The lesions developed a week before hospitalization and no respiratory symptoms were observed in this patient.¹⁹

A 12- year- old female presented with facial exanthema and a coated swollen tongue with pronounced papillae (strawberry tongue) when her fever had subdued after three days. The only other symptoms reported were fatigue and headache.²⁰  Three weeks after having a 5 day fever, along with coughing and prolonged diarrhea, a 9-year-old male developed symptomatic glossitis, along with other dermatologic symptoms and conjunctivitis.²¹ Of note, this patient had Down’s syndrome and alopecia areata universalis ²¹ unlike all the previous cases in which the children did not have any underlying illnesses prior to contracting COVID-19. The oral manifestation may therefore be atypical when compared to other children.

Table 2. Summary of studies showing the timing of oral manifestations relative to other symptoms in children with COVID-19 or MIS-C disease.

F-female, M-male

Length of time from onset of COVID-19 to the appearance of oral manifestations in patients diagnosed with MIS-C or Kawasaki disease.
A 6-month-old diagnosed with Kawasaki disease associated with COVID-19, presented with dry cracked lips (after 2 days of fever) and prominent tongue papilla (after 5 days of fever).²²

Fissured lips were observed in a 12-year-old male with a history of 6 days of fever along with other symptoms such as respiratory and gastrointestinal distress. Similarly, fissured lips was observed in a 5 year old female patient with a four day history of fever along with gastrointestinal symptoms, nuchal rigidity and swollen hands.²³ Another 9-year-old female patient developed fissured lips and strawberry tongue on the fifth day of hospitalization. Prior to her hospitalization, she presented with fever, and gastrointestinal distress.²³ It is important to note that all three cases were diagnosed as MIS-C.

In another case of a 10- year- old, male patient diagnosed with COVID-19 associated Kawasaki disease, a mildly erythematous oropharynx and slight fissured lips were observed after a 7 day period of fever. The patient also had a cough, rash, diarrhea, and conjunctivitis.²⁴

Similarly, a 3-year-old male who was admitted for having 8 days of fever, also showed no respiratory symptoms, but presented with glossitis, conjunctivitis, pulmonary involvement and other manifestations of the skin and was therefore diagnosed with Kawasaki disease.¹⁹

DISCUSSION
This literature review is a compilation of different cases in which oral manifestations were observed in children diagnosed with COVID-19.  Though the different reports included children of different ages and sex, it is unclear whether either play a role in the appearance of oral manifestations. Further studies should be carried out to investigate the potential role of age and sex as indicators for oral and other manifestations of COVID-19.

The most prevalent oral manifestations seen in children diagnosed with COVID-19 disease were hyperaemic pharynx and dysgeusia ⁽⁸⁾. Viral pharyngitis can result in this hyperaemic aspect of the pharynx which is consistent with an upper respiratory tract infection.⁸ Dysgeusia is thought to occur due to the presence of ACE 2 receptors for SARS-CoV- 2 on the oral and nasal mucosa.²⁵

On the other hand, children diagnosed with MIS-C the most common findings were changes in the labial mucosa^{7,10,11,12,13}, cheilitis⁹ and strawberry tongue.^10,13 Furthermore, oral mucosa changes were found to be the second most prevalent clinical findings (58%) in a metanalysis that included 318 COVID-19 pediatric patients diagnosed with MIS-C.²⁶

It is possible that given the severity of other symptoms in children with MIS-C that changes in the oral cavity go unperceived and so the incidence of oral manifestations may be undetected and thus underreported.⁷ It was noted that some of the oral manifestations seen in individuals with MIS-C were recorded as unspecified lesions, possibly due to the inability of medical physicians to correctly classify oral lesions. This potentially affects the true estimation of the prevalence of specific oral manifestations in persons with MIS-C. This is also coupled by perhaps the inability of small children to self-report symptoms, possibly leading to a lower prevalence of oral manifestations reported in the literature.⁸

It is likely that there are no particular oral manifestations associated with children infected with SARS-COV-2 but rather, oral lesions that may be seen in other common viral infections as well.⁸ Similarly to SARS-COV-2, many viruses may present different or the same clinical manifestations based on viral load, the type of variant, organotropism, host reaction and age.^{21, 27}

Fever is the main symptom seen in children ^4,28,29,30, this corroborates with the reported cases in which most children had a fever before later developing oral manifestations and other symptoms. In fact, in addition to fever and fatigue, oral and skin lesions may be the only clinical signs and symptoms of COVID-19 in children perhaps due to the increase in T cells which conveys some immunity against viruses.^20,31

CONCLUSION
Prevalent oral manifestations seen in children with COVID-19 were hyperaemic pharynx and dysgeusia. Common oral manifestations seen in those diagnosed with MIS-C were fissured lips, cheilitis and strawberry tongue. Based on a wide variation of symptoms and time of appearance, it cannot be concluded that the presence of oral manifestations could definitively be considered as a sentinel symptom. However, given the common belief that symptoms in children are usually less severe, the appearance of oral manifestations, in a child with COVID -19 like symptoms may be considered as a warning sign that the disease could potentially be more severe and have more serious outcomes, as in the case of MIS-C. Oral manifestations may be seen amongst the earliest manifestations of  acute COVID-19 in children, and may happen prior to presenting other symptoms. In the case of MIS-C, oral manifestations may occur up to a week after other manifestations of the disease. Dentists should be trained in recognizing the oral manifestations associated with SARS-COV-2 that could aid in the early diagnosis of COVID-19 in children or the potentially fatal MIS-C if left undiagnosed.

Ethical Approval statement: Not applicable
Conflict of interest statement: None declared
Informed Consent statement: Not applicable
Funding statement: None
Authors Contribution: Michelle Brown was involved in the initial conception, design of the study, collection of data and preparation and final revision of the manuscript. Xania Dawes assisted with the collection of data and final revision of the manuscript. Arvind Rajendra Santosh was involved with the initial conception of the study  and the final revision of the manuscript.

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