Some oral manifestations in patients with Covid-19

Abstract

Several oral manifestations of the oral mucosa have been reported in patients with COVID-19. The most frequent manifestations were xerostomia, lesions of the oral mucosa and taste disorders. Gingivitis and periodontitis have also been frequently diagnosed. There are many instances of patients developing oral candidiasis, especially those who have received high doses of antibiotics. Another commonly detected pathology is chronic recurrent aphthous stomatitis, the severity of which was proportional to the severity of the general infection.

Most of these conditions have been diagnosed in patients recovering from the SARS-CoV-2 infection, which stresses the importance of increased vigilance on the part of the dental practitioner towards post-COVID patients.

Keywords: Covid-19, oral mucosa.

We have entered the third year of the SARS-CoV-2 pandemic, the virus having spread in several waves. The recently emerged BA.2 subvariant is the newest challenge we are facing. The portion of the population that has had COVID-19 is constantly increasing. The high prevalence of infected people and the increasing evidence pointing to the involvement of oral structures have consolidated the relevance of this topic among dental practitioners, both in terms of protection and clinical protocols. Oral manifestations, especially in patients who experience a severe form, are serious and diverse. It is understood that oral pathologies occur in these patients due to a prolonged lack of proper oral hygiene, but also due to the general processes that occur in the body during the infection. Several authors have described the conditions of the oral mucosa in COVID-19 patients, covering a wide range of symptoms, from inflammation of the papilla of the Wharton’s canal to plaques on the tongue [5, 12, 16, 17, 18, 23, 31, 32, 46, 56].

To date, few studies that directly assess the prevalence of oral manifestations in patients with COVID-19 were published, Aragoneses et al. [5] identified 310 studies on this topic, not all of which used appropriate methods for detecting the disease. This creates a considerable risk of data polarization at this stage in time.

The relationship between these lesions and the pathophysiological processes caused by the SARS-CoV-2 infection is still being studied. A decrease in the natural resistance of the body after general intoxication could be one of the factors. Current evidence highlights the role of the angiotensin II conversion enzyme (ACE2) receptors that serve as a gateway for the virus into the cell [11]. Cells with a high ACE2 expression, such as respiratory epithelium, become target cells for viral particles, while also leading to concomitant inflammation of adjacent organs, thus presenting lesions in the salivary glands, oral and lingual mucosa [53]. It is thought that interleukin 6 (IL-6) may also play a key role in the occurrence of lesions [27].

Given the high viral load of SARS-CoV-2 in saliva, the direct effect of the virus on the epithelium cannot be ruled out [14]. Several studies have considered oral transmission to be a viable route of transmission [51], the validity of salivary specimens in the diagnosis of COVID-19 being investigated in several studies [22, 38]. This has led to a number of articles on the precautions and implications for dental practice during the COVID-19 pandemic [13, 24, 43]. Huang et al. [29] validated theories that the virus could manifest direct tropism for the oral epithelium and the salivary glands.

There is a substantial body of evidence pointing to the direct contribution of the virus and the pathological processes characteristic of COVID-19 to the occurrence of oral lesions [30]. However, these pathological manifestations may be caused by factors other than the direct effects of the viral infection. One cannot ignore iatrogenic lesions, which include those caused by the mechanical trauma of prolonged intubation and other invasive procedures used [39, 46]. Moreover, the role of pharmacological reactions in the formation of oral lesions was also considered [44]. Last but not least, given the large number of people affected by COVID-19, it is to be expected that some of the oral lesions observed in these patients will be a pure coincidence [5].

In some cases, COVID-19 creates associations of signs and symptoms involving several organ systems, which include the oral cavity. Some examples are multisystem inflammatory syndrome and Kawasaki disease, common in children with COVID-19 [6, 42]; toxic epidermal necrolysis, urticaria and angioedema [26]. In this case, the pathological processes go far beyond the limits of the oral cavity, which should be addressed in the context of than relevant clinical syndromes rather than separate oral manifestations of COVID-19 [5].

Regardless of the causes of these pathologies, the involvement of the dental practitioner is opportune.

The first descriptions of oral lesions in the patient with COVID-19 infection were reported by doctors in Brazil, who documented the case of a sixty-seven-year-old white man who tested positive for SARS-CoV-2 and presented oral manifestations such as recurrent herpes simplex, candidiasis and desquamative glossitis [31].

The occurrence of such opportunistic co-infections is to be expected in COVID-19 and cannot be directly attributed to the SARS-CoV-2 infection. Oral co-infections reported to date in patients with COVID-19 include candidiasis and Herpes simplex infections. The myriad drugs taken during treatment could adversely affect oral health, leading to opportunistic infections due to a compromised immune system and xerostomia. Obviously, these manifestations can be caused by the general condition of the patient, who concomitantly with COVID-19, present cardiac and renal pathology, kidney transplantation, which requires regular pharmaceutical treatment with immunosuppressants and anticoagulants.

One of the common symptoms of this infection is xerostomia [17]. It is well understood that under these conditions, the oral epithelium becomes receptive to various lesions and co-infections. Most studies that included this symptom were based on questionnaires, only the study conducted by Omezli et al. [35] used objective methods to measure salivary flow, finding a decrease of up to 18% [4]. In this regard, the decrease in salivary flow has been described as the main cause of xerostomia due to damage to the salivary glands. Other causes of xerostomia include nasal congestion and mouth breathing, nutritional deficiency, and anxiety and stress related to the pandemic or long-term hospitalization [1, 7, 47].

El Kady et al. noted a high prevalence of salivary gland damage, suspecting the potential tropism of the virus for acinar cells [18]. Sialadenitis leads to the activation of repair mechanisms via fibrosis. The proliferation of the virus in the salivary glands and the high viral load in the saliva could be a mechanism of transmission of the virus from asymptomatic patients [53], indicating the possibility of using saliva to diagnose the infection [50]. The neuroinvasive nature of SARS-CoV-2, with its negative effects on the peripheral nervous system could also induce hyposalivation [45]. The damage to the salivary glands manifested differently across patients: pain or swelling in the parotid or submandibular areas (13.8% and 10.3%, respectively), and 39.7% of patients reported “dry mouth” [18]. However, this inflammatory phenomenon also points to an immune response and the protective role of saliva [18, 20]. Wang et al. (2020) reported the presence of sialolithiasis in some patients with COVID-19.

Taste and olfactory disorders are often reported as an initial symptom of the disease. In mild forms of COVID-19, this may be the only symptom. Taste changes in COVID-19 are hypogeusia, dysgeusia and ageusia. [31, 52] The mechanism behind this symptom has not been fully elucidated. A high expression of ACE2 receptors has been identified in the oral mucosa, especially on the tongue, suspecting the infliction of direct damage to taste receptors [28, 34, 50]. On the other hand, the neuroinvasive nature of the virus may also lead to olfactory and gustatory disorders [40, 47]. Given the close functional link between taste and smell, most studies have interpreted olfactory and gustatory disorders as a single entity [25], making it difficult for the patient to distinguish between gustatory and olfactory dysfunctions [19]. Local inflammation cannot be ruled out as a causal factor of taste disorders, supported by the increased prevalence of this symptom in female patients, to whom hormonal features induce a more severe inflammatory response [31].

Among the lesions of the oral mucosa reported so far, we can include ulcers, erosions, blisters, plaque lesions, reactivation of HSV1 and geographic tongue. [5, 10, 18, 31]. They occur either before or alongside the systemic manifestations of COVID-19, regressing after 1-2 weeks [8].

Ulcerative lesions are often present in patients with COVID-19. [8, 19, 23]. The descriptions regarding the location and their configuration vary in the studies presented in medical literature. The most commonly affected sites are the dorsal part of the tongue and the lateral borders, followed by the hard palate and the oral mucosa [5]. They may be unique or grouped, the latter having a herpetiform or aphthous appearance with a diffuse erythematous base. Aphthoid ulcers can converge, forming large ulcers covered with yellow fibrin deposits, resembling lesions from erythema multiforme [21]. Bloody ulcers and crusts have also been reported on the labial mucosa, accompanied by palatal and gingival petechiae [12].

Vesiculo-bullous lesions are also encountered, most commonly in association with skin lesions [12, 19, 49]. Their preferred site is the tongue, followed by the soft palate. The most frequently observed lesions were erythema multiforme, being associated with the corresponding skin lesions [23].

Candidiasis-like lesions, both red and white, have also been reported. [23] Their preferred location is the dorsal part of the tongue and palate, often in association with multiple small ulcers, taste disorders, glossalgia and masticatory muscle pain [7, 21, 31]. These manifestations can occur as a result of immune depression as a result of antibiotic therapy, deterioration of general health and neglected oral hygiene [19].

Recovering patients with gingivitis and periodontitis have been documented in literature. Among the most common conditions are generalized erythematous and oedematous gingivitis, gingivo-periodontal bleeding, necrosis of the interdental papillae and squamous gingivitis [10, 19, 37]. These usually occur in severely ill patients with neglected oral hygiene during the period of incapacity. The symptoms disappeared 10 days after the administration of antibiotics and the use of mouthwash [19].

In the course of the disease, lesions of the lingual mucosa may occur, leading to the so-called “COVID tongue”, the most common being squamous glossitis – the geographic tongue. The mechanism behind the lesion has not yet been elucidated, with a hypothesis supporting the role of the proinflammatory cytokine interleukin 6 (IL-6), but this has not been confirmed yet [27, 56].

Another commonly detected pathology is recurrent chronic aphthous stomatitis, the severity of which is directly proportional to the severity of the supported SARS-CoV-2 infection. [55, 56].

Last but not least, halitosis was attested in 10% of the patients included in a cross-sectional study with 573 patients with COVID-19 [1]. The probable causes were poor hygiene, xerostomia, mucosal lesions and opportunistic co-infections.

For obvious reasons, due to the comparatively short duration of the COVID-19 symptoms, we cannot confirm the impact of the disease on the dynamics of dental caries. It is likely that changes in the macroorganism could alter the physiological processes of the pulpal organ, as it is not certain that they would return completely to normal after recovery.

In conclusion, we can observe that patients who have suffered from COVID-19 exhibit oral problems. Regardless of whether these are primary pathological manifestations in the oral cavity or are caused by other secondary factors, the involvement of the dentist in their treatment is appropriate. Subsequent research will establish the causes and mechanisms behind the occurrence and development of oral lesions in COVID-19 patients, which will also lead to the specification of the treatment of each form and will provide screening indices for patients.

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