Introduction
The COVID-19 pandemic, which emerged in Wuhan, China, has presented a significant global public health crisis, affecting the majority of nations worldwide. The global effect has been significant due to its mechanisms of transmission, the subsequent development of severe acute respiratory syndrome, and the global mortality rate that followed the onset of the pandemic (1).
The World Health Organization (WHO) officially proclaimed a state of public health emergency on January 30, 2020(2). Subsequently, the virus has spread in >223 nations and regions, leading to a worldwide pandemic, with >700 million cases and almost 7 million deaths, as of October, 2023(3).
Laboratory genomic analysis demonstrated that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for COVID-19, shares a 96% overall genomic similarity with a bat coronavirus known as CoVZXC21 (RaTG13) (4). Additionally, there is a significant similarity of 80% sequence identity between this newly identified coronavirus and the SARS coronavirus (SARS-CoV-1), which caused the previous SARS pandemic in the past (5). The angiotensin-converting enzyme 2 (ACE-2) receptor in humans serves as the primary point of viral entrance into the human body. Notably, a single nucleotide substitution (Arg426 to Asn426) has been found to enhance the binding affinity of the new virus, perhaps accounting for its heightened transmissibility (6). SARS-CoV-2 mostly manifests as a respiratory virus (7). Consequently, the primary mode of transmission for this pathogen is the direct contact with Flügge's droplets from an individual infected that has symptoms, which are transmitted via coughing, sneezing or exhaling (8). The expression of ACE-2 receptors is higher in the small intestine, which may account for the presence of gastrointestinal symptoms observed in some of patients. There is a vast amount of evidence that supports the existence of viral genetic material in the stool of patients, hence establishing the fecal-oral pathway as a mechanism of transmission and spread of the virus (9).
The use of infection control measures is critical for controlling the transmission of the virus and for effectively managing the ongoing outbreak. The risk of infection between patients and dental practitioners may be greater in dental environments due to their specific features (10). Considering the probable impact of COVID-19 on dental practices and hospitals, there has been an urgent need for the implementation of rigorous and efficient infection control policies (11).
In combination with fever, fatigue, dry cough, myalgias, a sore throat, breathing difficulties and respiratory issues that can lead to severe acute respiratory syndrome, patients with COVID-19 may experience a diverse range of additional local and systemic complications (12). These include acute cardiac damage, acute renal failure, gastrointestinal complications, dysgeusia, anosmia and neurological symptoms (13).
The oropharyngeal microbiome, which is the community of organisms that colonizes the upper respiratory tract, can influence the clinical progression of respiratory viral infections, including SARS-CoV2, and the virus may be identified in saliva and oropharyngeal secretions (14). Aphthous-like ulcers and superficial necrosis were seen in individuals who had been diagnosed with COVID-19, as these lesions develop in areas that are recognized to possess ACE-2 receptors, such as tongue epithelium and salivary gland tissue, following the occurrence of dysgeusia (15).
Discussion
The mode of transmission refers to the mechanism by which a disease or infection is spread from one individual to another (31). Based on the data derived from genetic and epidemiological studies, it is evident that the onset of the COVID-19 epidemic may be attributed to an initial instance of zoonotic transmission, subsequently leading to continuous human-to-human transmission (32). It is well known that the transmission of the virus mostly occurs via the upper respiratory tract (33). Furthermore, it is worth noting that there exists a potential for fecal-oral transmission, since scientific investigations have successfully detected the presence of SARS-CoV-2 in the feces of individuals originating from China and the USA (34).
A significant proportion of individuals had symptoms such as fever and dry cough, with a subset of patients also presenting with shortness of breath, exhaustion and other non-typical manifestations, including muscular pain, disorientation, headache, sore throat, diarrhea and vomiting (35). In a previous study, in a cohort of individuals who underwent a chest CT scan, the majority of patients had bilateral pneumonia, with the prevailing patterns being characterized by ground-glass opacity and bilateral patchy shadows (36).
A wide range of signs and symptoms have been linked to COVID-19, including dysgeusia and anosmia, even in cases when respiratory symptoms are not present. Olfactory and gustatory impairment are symptoms commonly observed in individuals diagnosed with COVID-19 and may serve as early indicators throughout the progression of the infection. The heightened knowledge of this fact has the potential to promote early diagnosis and treatment, as well as enhance vigilance in preventing viral transmission (37).
The present study demonstrated that 23% of the patients with COVID-19 had an altered perception for sweet and spicy taste, 25% experienced a change in the perception of salty taste, 21.2% reported a change in the sour taste, and no subjects in the control group reported any such changes. These results are in accordance with those from the study by Cattaneo et al (38), where ~45% of the patients in the COVID-19 group had symptoms concerning taste and smell, including the loss of olfactory or gustatory abilities. By contrast, none of the individuals in the control group reported experiencing these symptoms (38).
Salivary secretion is often compromised following infection with SARS-CoV-2, leading to the prevalent manifestation of xerostomia as the predominant oral symptom in individuals afflicted with COVID-19(39). The study conducted by Chen et al (39) demonstrated that xerostomia was present in >46% of the patients examined. They did not find any significant sex differences in the prevalence of xerostomia (39). Individuals diagnosed with xerostomia commonly exhibit a range of symptoms in addition to their primary complaint of oral dryness (40). These accompanying manifestations include a sensation of burning, altered taste perception (dysgeusia), inflammation at the corners of the mouth (angular stomatitis) and dysphagia (41). Although xerostomia is not fatal, it can significantly affect the quality of life and oral health of individuals (42).
As regards all the above, the present study revealed that in the COVID-19 group, between 30 to 44% of patients indicated tonsillitis, pharyngitis and oral cavity bleeding. On the other spectrum, a mere 1.9% of patients indicated the presence of glossitis, while ~11 to 15% reported periodontal pockets and abscesses. As regards the control group, the prevalence of oropharyngeal symptoms was generally lower compared to that in the COVID-19 group, apart from glossitis, tonsillitis, pharyngitis, hemorrhage, periodontal pockets and abscesses. These results are similar to the findings reported by other researchers, whose study revealed that glossitis was observed in both groups (positive and negative RT-PCR test groups) with similar relative frequencies (29).
It is worth noting that sialadenitis can also be observed in patients. In the study conducted by Fisher et al (43), the patient exhibited clinical manifestations indicative of concurrent acute bacterial suppurative parotitis and viral parotitis. Another study documented three instances of parotitis associated with COVID-19, and patients presented with unilateral ear pain and retromandibular edema, and magnetic resonance imaging revealed the presence of intracarotid lymphadenitis (44).
Parotitis refers to the inflammatory condition affecting the parotid glands, which are the most often affected major salivary glands (45). It has the potential to be either a localized condition or as a symptom of a broader systemic inflammation (46). Etiology may be attributed to several factors, including duct blockage (such as sialolithiasis), the presence of infectious agents, or inflammatory processes (Sjogren syndrome, rheumatoid arthritis, systemic lupus erythematosus) (47). Friedrich et al (48) found out that certain individuals diagnosed with COVID-19 have reported instances of salivary gland enlargement that affected the parotid glands. Even though the precise etiology of parotid gland enlargement in individuals with COVID-19 is still not fully clarified; nonetheless, it is suggested that this phenomenon may be associated with inflammatory processes, viral replication inside the salivary glands, or an immune-mediated reaction (49).
The present study demonstrated that infection was also associated with several skin facial and oral manifestations. Abscesses and other lesions accounted for 15 to 23% in the COVID-19 group and 13 to almost 27% in the control group. These slight differences between the two groups are in line with the findings reported in the literature. In their study, Nuno-Gonzalez et al (50) analyzed 666 patients over a 2-week period and concluded that 45% of them had various mucocutaneous manifestations. Of these patients, >25% had oral lesions, and swelling on the tongue was most commonly identified, followed by inflammation, redness of the tongue and canker sores. Several patients also reported a burning sensation in the mouth or a loss of taste. However, the oral symptoms proved to be temporary (50). These symptoms are not surprising, as it is common for viruses to cause both skin rashes and changes in the mucous membranes, such as ulcers or spots in the oral cavity (51).
According to experts, it is likely that these cases of tongue-COVID are not reported, as in some situations, doctors do not ask patients to open their mouths to examine their oral cavity, as such an examination increases the risk of infection. In addition, patients usually keep the mask on their face, as this protective measure is crucial to reduce the spread of the virus (52). In the present study, a reduction in olfactory and gustatory capacities individuals diagnosed with COVID-19, as compared to those who did not report such alterations. It was found that a considerable proportion of patients, ranging from 21 to 25%, indicated the presence of either olfactory or gustatory impairment. These findings are similar to another literature review that analyzed 10 studies describing olfactory dysfunction in a sample size of 1,627 individuals (53). That study (53) revealed a prevalence rate of >52% among patients diagnosed with COVID-19. In the same research, Tong et al (53) further examined nine studies to assess the occurrence of gustatory dysfunction, with a sample size of 1,390 individuals. This analysis also revealed a prevalence rate of almost 44% among the study group. The researchers performed subgroup analyses on studies that assessed olfactory dysfunction using both non-validated and validated instruments (53).
Further research led Amorim Dos Santos et al (54) to observe that ~21% of individuals diagnosed with COVID-19 had developed various oral mucosal lesions, which is a lower prevalence compared to dysgeusia and xerostomia. In that study, a significant proportion of individuals displayed oral mucosal lesions at ~10 days following infection. Subsequently, these patients commonly received treatment involving photo-biomodulation therapy and/or antiviral medication within a timeframe of 1 to 3 weeks (54). In addition to this conclusion, Iranmanesh et al (55) mentioned that individuals who are elderly, or those that have been hospitalized for an extended period of time, or exhibit poor hygiene practices, have diabetes, or are at an increased risk of developing oral mucosal lesions.
Likewise, these individuals often experience more severe, persistent and extensive oral lesions. These findings present a high prevalence of oral manifestations, including lesions such as aphthous, herpes, Kawasaki, plaque, fungal infections such as candidiasis and mucormycosis, mucosal petechiae, ulcers related to herpes simplex virus reactivation, oral herpes zoster, gingivitis and bleeding gums (56-59).
The present study had certain limitations which should be mentioned. The younger and more digitally engaged demographic has a greater propensity for social interaction, and this subgroup appears to be less susceptible to the impacts of COVID-19 in comparison to older cohorts, who have higher rates of illness and death (60).
Cross-sectional surveys may be susceptible to bias due to several factors, including the effect of confounding variables, variations in the timing of patient assessments in relation to their exposure, and potential reporting bias (61). In these investigations, such as the present study, the researchers are primarily presenting patient characteristics and their corresponding symptoms, rather than focusing on treatments, interventions, and their following impacts or outcomes (62).
This observational approach may contribute to the reduction of observer bias. When conducting research that relies on historical data obtained from patients, there exists a potential for memory bias and the under-reporting or errors of symptoms, particularly in relation to the timing and duration of symptoms (63).
In conclusion, impairment in olfactory and gustatory functions is often observed in individuals diagnosed with COVID-19, perhaps serving as early markers of disease progression. These manifestations were more frequent in the COVID-19 group, during SARS-CoV-2 infection compared to the control group. Compared to the control group, the COVID-19 group typically had a decreased prevalence of oropharyngeal symptoms, apart from oral cavity discomfort (30.8%), tonsillitis (17.3%), bleeding (34.6%), tooth colour changes (36.5%), recurrence (15.4%), and abscesses (7.7%). These symptoms were not associated with the severity of the disease, nor with the administration of cortisone therapy or antiviral therapy.
These manifestations may be an early sign of the disease and, taken into account, could lead to an early diagnosis, which would limit the transmission of infection in dental offices.