43 minute read
Dentistry in the Context of COVID-19 : Oral Pathologists’ Perspectives Based on a Compilation of Data
Paulo Victor Mendes Penafort, DDS; Tayná Figueiredo Maciel, DDS; Ana Paula Ferreira Souza, DDS; Tássia Caroline da Costa Mendes, DDS; Renata Gualberto Cunha, DDS, MSc; Naiza Menezes Medeiros Abrahim, DDS, MSc; Lucileide Castro Oliveira, DDS, MSc; Jeconias Câmara, DDS, MSc; Paulo Henrique Braz-Silva, DDS, PhD; and Tatiana Nayara Libório-Kimura, DDS, PhD
ABSTRACT A review of articles related to SARS-CoV-2 indexed in databases, primarily PubMed, from December 2019 to August 2020 as well as historical support literature was conducted addressing relevant aspects that oral pathologists, stomatologists and general dentists need to be aware of in the context of the COVID-19 pandemic. The discussion was based on the contextualization of general aspects as a basis for understanding of the scenario dental professionals are currently facing.
AUTHORS
Paulo Victor Mendes Penafort, DDS, is an oral an maxillofacial pathology resident at the Federal University of Amazonas.
Tayná Figueiredo Maciel, DDS, is an oral and maxillofacial pathology resident at the Federal University of Amazonas.
Ana Paula Ferreira Souza, DDS, is an oral and maxillofacial pathology resident at the Federal University of Amazonas.
Tássia Caroline da Costa Mendes, DDS, is an oral and maxillofacial pathology resident at the Federal University of Amazonas.
Renata Gualberto Cunha, DDS, MSc, is an assistant professor and preceptor of the residency program of oral and maxillofacial pathology at the Federal University of Amazonas.
Naiza Menezes Medeiros Abrahim, DDS, MSc, is an assistant professor and preceptor of the residency program of oral and maxillofacial pathology at the Federal University of Amazonas.
Lucileide Castro Oliveira, DDS, MSc, is an assistant professor and preceptor of the residency program of oral and maxillofacial pathology at the Federal University of Amazonas.
Jeconias Câmara, DDS, MSc, is an adjunct professor and coordinator of the residency program of oral and maxillofacial pathology at the Federal University of Amazonas.
Paulo Henrique Braz-Silva, DDS, PhD, is an assistant professor in the department of stomatology in the School of Dentistry and in the laboratory of virology at the Institute of Tropical Medicine of São Paulo, School of Medicine at the University of São Paulo.
Tatiana Nayara Libório-Kimura, DDS, PhD, is an associate professor in the department of pathology and legal medicine and vicecoordinator of the residency program of oral and maxillofacial pathology at the Federal University of Amazonas in Manaus, Brazil. Conflict of Interest Disclosure for all authors: None reported.
The new coronavirus pandemic has become a true challenge for health professionals around the world, significantly affecting dental practitioners in private offices, universities and research institutes. [1,2] The World Health Organization (WHO) declared this pandemic on March 11, 2020, [3] and according to data from June 22, 2020, there were 8,860,331 confirmed cases of COVID-19 worldwide at that time, including 465,740 deaths, as reported by the WHO. [4]
Despite the increasing rise in studies on COVID-19 in both medical and dental contexts, little is known about the possible general effects of the disease in view of the countless variables related to geographical aspects, type of affected population, individual immunity and profile of the response to the proposed treatments. In addition, a possible genetic predisposition to the disease has been recently raised that individuals with blood type O would be more protected than those with blood type A, who would be at higher risk. [5,6]
There is no treatment for the disease, and the therapeutic perspectives are based on existing drugs used for other diseases. Given the severity of the pandemic, the optimal design for clinical trials is faced with an unfavorable scenario due to recruitment difficulty, methodology for control group design and steps of blinding and randomization, which make it even more difficult to establish an effective treatment compatible with the majority of the population. [7,8]
In this sense, the most viable way in the context of dentistry is to find the pathogenic mechanisms of the disease, its local and systemic effects and how they affect oral medicine and pathology. From this, it is possible to contribute to the guidance of clinical practices, routine laboratory tests and histopathological reports in accordance with biosafety issues. [2,9]
It is important to know not only the disease, but also the possible treatments available (even if not proven), as they may or may not have oral repercussions requiring attention during the diagnostic process. Also, the underlying disease itself may affect oral soft tissues in which vesicular-bullous lesions, ulcerated wounds, aphthous-like ulcerations and erythematous macules are the current signs. [10–17] In addition, saliva contains biomarkers that are used to diagnose several diseases, thus being a promising source in the context of COVID-19.
We have provided information about the history of coronavirus in the context of pandemics, general aspects of SARS-CoV-2 and signs and symptoms of the disease including extrapulmonary manifestations. Despite the scarcity of published studies on the relation between dentistry and COVID-19, especially in the field of oral pathology, we provide information on oral manifestations observed in patients with COVID-19 and on emerging potential treatments of the disease, including possible implications to oral mucosal lesions with which dentists should be familiarized. We also present aspects of dental practice related to COVID-19 and the oral pathology practice in the context of COVID-19.
History of Coronavirus in the Context of Pandemics
Since the beginning of the 21st century, viruses of the Coronaviridae family have been responsible for diseases characterized by serious damage to the respiratory system, [18] causing flulike symptoms and acute respiratory distress. These viruses emerged in China in 2002, resulting in a pandemic of severe acute respiratory syndrome (SARS) caused by SARS-CoV. [19]
In June 2012 in Saudi Arabia, a man attended a health service and reported common cold symptoms and shortness of breath similar to those found in the 2002 SARS pandemic. The man died of acute pneumonia and renal failure. A novel coronavirus was isolated from his sputum and was named MERS-CoV and is the virus responsible for Middle East respiratory syndrome (MERS). [20,21]
A study on the 2003 SARS pandemic published in 2007 drew attention to the possibility of a resurgence of SARS through genetic recombination. This might happen in southern China where there is a local culture of eating exotic mammals, such as bats, that are a major reservoir of these viruses. Thus, the need to prepare for a new pandemic should not be ignored. [22]
In December 2019, approximately 18 years after the first pandemic caused by a coronavirus, health officials from Wuhan City, China, reported cases of patients with pneumonia of unknown cause. [23] In January 2020, using samples of bronchoalveolar lavage fluid from these patients, the genome of the novel β genus coronavirus was identified. Initially, the virus and disease were named 2019-nCoV and novel coronavirus-infected pneumonia (NCIP), respectively. [24] On Feb. 11, 2020, the virus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on its genetic similarity to the coronavirus responsible for the 2003 SARS pandemic, and COVID-19 was the name assigned to the disease. [25] In less than three months, this disease spread rapidly to the rest of the world, causing the WHO to declare a pandemic on March 11, 2020. [3]
General Aspects of SARS-CoV-2
SARS-CoV-2 belongs to the family of coronaviruses and corresponds to the seventh member of the group, presenting a genetic compatibility of 70% with SARS-CoV. [1]
Angiotensin-converting enzyme 2 (ACE2) is a protein that acts as a viral receptor for SARS-CoV-2. [26] This receptor was found in approximately 72 types of human tissue through realtime polymerase chain reaction (RTPCR). [27] Studies show that this receptor is expressed on the surface of several cell types and is found more in alveolar epithelial cells of the lung and in small intestine enterocytes. In the nasal and oral mucosa and nasopharynx, this receptor was found in the basal layer of nonkeratinized squamous epithelium. [28]
The laboratory diagnosis consists of the detection of viral RNA found in respiratory tract samples collected from infected patients using RT-PCR examination. [1]
Virus Transmission and Signs and Symptoms of the Disease
In a study of 181 patients with COVID-19 whose period of transmission and onset of symptoms were detected, the average incubation period for the virus was 5.1 days. [29] The transmission of the virus occurs from person to person through respiratory droplets that are expelled during speech or sneezing, causing a very quick spread of the disease. [1]
The symptoms found in patients affected by COVID-19 include fever (in most cases), coughing (the second most common symptom), myalgia or fatigue, expectoration and dyspnea. Other symptoms can be found in a minority of cases, such as headache or dizziness, diarrhea, nausea and vomiting. There is, however, the possibility that individuals can carry the virus without developing symptoms, which are asymptomatic cases, and this group presents a danger to the dynamics of virus transmission. [30–32] A recently accepted publication using a smell and taste questionnaire was carried out in 12 European hospitals by Lechien et al. (2020). Of the 417 European patients with mild to moderate symptoms of the disease, 85.6% and 88.8% reported olfactory and gustatory dysfunctions, respectively. [33] Although these results were criticized, the authors reinforced the previously published information and highlighted that a majority of these patients were not hospitalized and the prevalence of smell and taste loss was based on a reliable self-reported questionnaire. [34]
A brief communication published on April 27, 2020, draws attention to symptoms such as ageusia and anosmia, which may be the first symptoms or the only ones, especially in patients with few symptoms of COVID-19. [35] A study of 72 COVID-19 patients found the presence of chemosensitive disorders in 73.6% of them, of which 60 patients had various degrees of hyposmia and two patients had anosmia. Taste evaluation revealed hypogeusia in 33 patients and complete ageusia in one patient. [36] A case series regarding oral lesions in patients with COVID-19 drew attention to the oral cavity as a target organ for SARS-CoV-2 based on the important role of the ACE2 receptor in the virus cellular entry; therefore, the development of dysgeusia and anosmia in the course of SARSCoV-2 infection could be an early event. For this reason, these manifestations could be considered a possible disease marker by dentists working on the front lines of the pandemic. [17]
With focus on the new-onset dysgeusia as a potential early marker of COVID-19 infection, a letter to the editor from Lozada-Nur et al. (2020) raised some new questions regarding dysgeusia as a prognostic marker for the severity of COVID-19, possible factors (including medical conditions, medications) that could modify the severity of dysgeusia and also if patients’ characteristics (such as age, sex, ethnicity and severity of COVID-19) could be related to dysgeusia occurrence. These questions will likely be answered in future studies. [37]
In parallel, these same authors [37] proposed some mechanisms for the establishment of dysgeusia in patients with COVID-19. These mechanisms could be related to several aspects such as direct infection of salivary glands by SARS-CoV-2, possible neurological nature, including direct damage to cells that express ACE2 of the taste buds and peripheral neurosensory chemoreceptors of the taste, also an inflammatory mechanism and oxygen deficiency (hypoxia). Finally, the authors hypothesized that due to an immune response to SARS-CoV-2 viral replication, dysgeusia may arise based on changes in localized cellular zinc homeostasis in oral gustatory cells accompanied or not by hypozincemia. In addition, once the olfactory epithelium is affected by the virus, taste can also be altered, as it is closely linked to the sense of smell.
Approximately 80% of the infected patients develop a mild form of the disease, but about 1 in 5 can progress to severe pulmonary involvement, especially the elderly and/or those with comorbidities. [38]
Extrapulmonary Manifestations of COVID-19
Many studies reporting the presence of extrapulmonary manifestations of COVID-19 have been published, as the disease leads to a systemic infection, facilitating its spread throughout the human body. Viral involvement of the central nervous system, for example, can lead to symptoms such as dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia and seizure. [39]
Histopathological analysis of a liver sample taken from a patient who died of COVID-19 revealed the presence of microvesicular steatosis and mild lobular and portal activity, suggesting hepatic impairment due to both viral infection and reaction to the drugs used for treatment of the disease. [40]
A study of urine samples from 333 patients with COVID-19 revealed renal involvement in 75.4% of the cases (251 of 333). Proteinuria, hematuria and acute renal failure were the most common findings. Renal complications in patients with COVID-19 are associated with a high risk of mortality. [41]
Expression of the ACE2 receptor in the intestinal epithelium and the infection by SARS-CoV-2 have been associated with gastrointestinal manifestations of coronavirus disease. Diarrhea is the most common symptom, with an occurrence rate ranging from 2% to 50% in studies of COVID-19 patients. This symptom may even precede respiratory symptoms. [42]
Histopathological analysis of a heart sample taken from a patient who died of COVID-19 did not show any major damage to cardiac tissue, only a few mononuclear inflammatory infiltrates in the interstitium. [40] The mechanism by which SARS-CoV-2 causes damage to the myocardium is not well established. It is known that the virus acts through ACE2 receptors and that patients with cardiovascular diseases have a worse prognosis and need special treatment. [43]
Hematological changes were mainly found in patients with a severe form of the disease. In these patients, the lymphocyte count in adult patients may be lower than in patients with the mild form. Other findings in these patients include coagulation indices, such as prothrombin time, activated partial thromboplastin time and D-dimer, which can show higher levels. [32]
Oral and Skin Manifestations Found in COVID-19
Cutaneous and oral manifestations have been increasingly associated with COVID-19. There are myriad studies on clinical presentations, but few attempts to standardize these lesions are observed.
Recalcati (2020) was one of the pioneers in observing the concomitance of exanthematous lesions and virus infection in which 20.4% of the 88 patients developed skin lesions (i.e., erythematous rash), generalized urticaria and chicken pox-like vesicles. [44] Fernandez-Nieto et al. (2020) evaluated 24 patients who tested positive for SARSCoV-2 by means of a nasopharyngeal swab and reported the appearance of lesions, such as small papules, vesicles and pustules of various sizes, classified into two patterns. [45] Vesicular lesions were predominant, representing 54.5% of the 22 patients evaluated. It is speculated that pseudochilblain and vesicular lesions may be indicators of the disease. [46,47]
The common microscopic findings in cutaneous biopsies of vesicularbullous lesions proved to be nonspecific, and the lesions do not appear to have pathognomonic characteristics differentiating them from other viral infections with cutaneous manifestations. Therefore, the possibility of dermatological side effects of the drugs used in patients for treatment of the disease should be considered. [48]
Lesios mimicking the rash pattern like those found in Steven-Johnson syndrome (SJS) have been seen on the skin of patients infected with SARSCoV-2. The oral cavity of patients with SJS is frequently affected, and according to the above-mentioned mimetic pattern, similar oral lesions may appear in patients infected by COVID-19. The use of the drug imatinib may have played a role in the appearance of this manifestation in the patient studied by Lagziel et al. (2020). [49]
Vesicular-bullous lesions, ulcerations, macules, aphthous-like lesions and petechiae were also reported in the oral cavity of suspected and infected patients. However, reports and reviews are brief compared to those of cutaneous manifestations. Based on our search as of August 2020, approximately eight authors had reported oral lesions suspected to be associated with COVID-19, some with concomitant skin lesions. As the inferences about the viral etiology of SARS-CoV-2 are recent, a standardization of the clinical characteristics cannot yet be established. [10–17]
In the oral cavity, Martín CarrerasPresas et al. (2020) described lesions in three potential COVID-19 patients; two were suspected cases based on symptoms but had not been tested for SARS-CoV-2. One of these patients had lesions similar to herpetic stomatitis and the other had multiple small ulcers on the palate. However, the third patient, who was positive for SARS-CoV-2, developed blisters on the internal lip mucosa and desquamative gingivitis. [13]
A series of cases reported by Brandão et al. presented eight patients infected with COVID-19, who presented oral ulcerations after symptoms of dysgeusia in most of them. Oral manifestations in these patients included painful oral necrotic ulcers and aphthous-like ulcerations that affected the tongue, lips, palate and oropharynx. The study also shows the relationship between SARSCoV-2 and ACE2, the main receptor of the SARS-CoV-2 host cell, expressed in epithelial cells of the tongue and of the salivary glands, showing that this virus, may be implicated in the development of dysgeusia in patients with COVID-19. The author also hypothesized that after infection of the oral keratinocytes/ glandular tissues, there is an increase in the permeability of the cell walls to foreign pathogens and viral replication in the cells lining the oral mucosa, leading to ulcers and necrosis. However, future studies are necessary to discover if these oral ulcerations are directly caused by the virus or if they are a coincidental event in COVID-19 progression. [17]
Jimenez-Cauhe et al. (2020) reported on patients with erythema multiforme-like lesions in which the oral cavity of three of them showed macules on the palate and petechiae, whereas one developed skin lesions at the same time. Studies of hematological impairment in COVID-19 patients revealed possible thrombocytopenia. Such information should be explored, as it could be correlated with the appearance of petechial lesions. [12]
In our literature review, we present reports on skin and mucocutaneous manifestations in patients diagnosed with COVID-19 and histopathological characteristics of some of these lesions (TABLE). Nevertheless, it is possible that in some of these reports COVID-19 has not been properly diagnosed.
Potential Treatments and Their Implication to Oral Lesions
A treatment protocol for COVID-19 is not yet established. In an attempt to alleviate the symptoms, drugs used for other diseases have been investigated. Wu et al. (2020) carried out a literature review to list the plausible drugs used to treat COVID-19 by separating them into groups of antiviral agents and supporting agents, among others. The efficacy of these treatment regimens remains to be verified by appropriately designed clinical trials. [7,8]
Among current potential drugs, chloroquine, hydroxychloroquine and tocilizumab can cause adverse effects on oral tissues in other pathological contexts. For this reason, we will discuss these drugs in more detail.
Chloroquine and Hydroxychloroquine
Chloroquine (CQ) and hydroxychloroquine (HCQ) have been tested in the treatment of COVID-19, in which both are considered broadspectrum antiviral drugs. [50] These drugs are generally safe and routinely used to treat immunological, dermatological and rheumatological disorders [51–56] including malaria. [47]
The potential adverse events of CQ and HCQ include retinopathy, cardiotoxicity and myelotoxicity, which are rare, and a cumulative dose-dependent effect in patients with rheumatoid arthritis and connective tissue disorders. [51–56]
The chronic use of CQ has been associated with hyperpigmentation of the oral mucosa in the palate region, [57] but this effect is observed in patients who use this drug for more than six months. [51–54,58] Mucosal hyperpigmentation may also be a sign of underlying systemic disease or a side effect of drug therapy. [51,53,54]
Although not supported by the literature, CQ and HCQ have been used in the treatment of SARS-CoV-2 for a short period of time, according to expert consensus. [50,59] Therefore, based on the present literature review, the authors consider that there is a low risk of oral pigmentation at the doses and time of use studied. However, considering SARS-CoV-2 and the diversity of protocols and doses used, precaution is recommended with observation for possible oral implications resulting from their use in the current treatments.
Tocilizumab
Tocilizumab is an important interleukin-6 (IL-6) receptor inhibitor that may be associated with osteonecrosis of the jaws; thus, caution should be taken when using this drug in patients with COVID-19. [60] Tocilizumab was originally used for treatment of rheumatoid arthritis and was recently considered for treatment of COVID-19. Studies have associated the chronic use of tocilizumab with osteonecrosis of the maxilla, associated or not with bisphosphonates. [60,61] It is unlikely that tocilizumab would cause changes in the oral tissues of patients with COVID-19, as this drug is normally used for a short period of time, but caution should be taken because this disease is new and its actual behavior in response to the current treatments is not well known.
Other Medications and Their Possible Oral Implications
Other drugs are being empirically used for the treatment of COVID-19, especially remdesivir, nitazoxanide, ivermectin, anticoagulants (enoxaparin) and corticoids (dexamethasone). [7,62–66] However, in our literature review, no other possible direct adverse effects from these medications in the oral cavity were found. On the other hand, erythema multiforme-like lesions were reported in four patients with COVID-19; three of the patients showed palatal macules and petechiae during intraoral examination. The medications used for these patients were lopinavir/ritonavir, HCQ, azithromycin, corticosteroids and ceftriaxone. The authors emphasize the need for more investigation into the role of the virus, including drug intake or any other conditions associated with these lesions. [12]
Speculations Based on Reported Oral Manifestations Triggered by Medications
It is important to highlight that several medications have the potential to cause adverse effects in the oral cavity, including salivary glands [67] and oral mucosal tissues. Among some common oral adverse effects related to medications, it is possible to cite xerostomia, hairy tongue, [68,69] lichenoid reactions and others.
Xerostomia has been reported to be an effect of myriad medications, such as antiviral agents, corticosteroids and antibiotics. [69,70] The disruption of the normal homeostasis of the oral cavity may cause a range of oral diseases, including dental caries, oral candidiasis, taste disturbance and difficulties with chewing, swallowing and speaking. [70] The use of corticotherapy can predispose to candidiasis. [71]
Another condition is oral hairy tongue, which has been implicated with the use of many antibiotics such as penicillin, erythromycin and linezolid. Medications predisposing individuals to xerostomia are associated with hairy tongue, and there are also reports that prednisolone can be implicated with causing this manifestation. [68] The mechanism of drug-induced oral hairy tongue is not known. Moreover, xerostomia may be capable of causing this pathology when combined with other predisposing factors, such as smoking and poor oral hygiene. [72]
These above-mentioned situations could serve as a basis for a biological reasoning for some empirical drug treatments that may arise in future studies. In the dental context, this should also draw attention to the possible oral implications of medications in terms of side effects.
Saliva: Clues to Diagnosis and Disease Prediction
Salivary biomarkers have recently been used to diagnose various diseases, such as oral cancer, periodontal diseases, dental caries, lung cancer, breast cancer and diabetes. [73] Consistent studies have shown the presence of SARS-CoV-2 in human saliva, indicating that this fluid is a viable tool for diagnosing patients who feel discomfort with nasal and oropharyngeal swabs, in addition to decreasing the risk of contamination of health care workers during sample collection. [74–81] Samples of saliva can be stored at –80 C for several years with little degradation. This means that saliva can be used in future analyses and serve as a prognostic marker for COVID-19 during different stages of the infection, thus being possible to follow the progression of the disease. [82]
In our literature review, we found several studies reporting relevant results regarding the detection of SARS-CoV-2 in human saliva, with a concordance rate ranging from 81.8% to 100% compared to other detection techniques such as nasal and oropharyngeal swabs. [74–76,79,80]
A study conducted in Hong Kong examined saliva samples collected from COVID-19 suspect patients after two days of hospitalization on average (variation from zero to seven days). The authors reported concordance rates of 91.7% for positive results compared to nasopharyngeal swab and of 100% for 33 negative results. Culture method showed the presence of live virus in three saliva samples, indicating the transmission potential of COVID-19 through saliva. [75] Another study carried out in Italy showed a concordance rate of 100% between saliva samples and nasopharyngeal swab for positive results of SARS-CoV-2, which was detected by RT-PCR. Also, two patients testing positive in the same days were considered negative after detection with nasopharyngeal swab or bronchoalveolar lavage. [77] In these cases, although nasopharyngeal swab had detected no virus, individuals might be infected, as the virus was present in the salivary glands. In fact, these glands are potential targets of SARS-CoV-2 because glandular cells express the receptor of angiotensinconverting enzyme 2 (ECA2). [79,83–85]
Some articles provide information on viral load monitoring in saliva for detection of SARS-CoV-2 in humans. [74–80] Azzi et al. (2020)[77] also highlighted the value of saliva in the clinical evolution of COVID-19, as there was an inverse association between lactate dehydrogenase (LDH) and cycle threshold (Ct) values. The results found in a cohort study performed by To et al. (2020) [74] showed that despite the development of antibodies against surface proteins of SARS-CoV-2, viral RNA could still be detected in oropharyngeal saliva samples over several days. Moreover, the salivary viral load was found to be higher during the first week of symptoms, decreasing in onethird of the patients over time (20 days or more). In a specific patient, viral RNA was detected 25 days after the onset of symptoms, suggesting that these findings are important for guiding antiviral treatments. Therefore, it is necessary to perform more studies for standardization of saliva tests to detect COVID-19 and follow its evolution. The main advantages of using saliva for diagnosis of COVID-19 and other diseases are that its collection is fast, easy and low cost, thus posing less risk of contamination for health care professionals, and it is well accepted by patients. In addition, serial saliva samples can be used to follow the evolution of the infection because saliva deteriorates less over time. [74,84–86]
The U.S. Food and Drug Administration (FDA) has recently approved a test using saliva for diagnosis of COVID-19. A sample of saliva is collected by the patient spitting into a tube under the supervision of a qualified practitioner; the material is analyzed based on the TaqPath SARS-CoV-2 assay, which is used in COVID-19 tests available to identify viral RNA. [87]
Despite the importance of diagnosing COVID-19 using saliva, one cannot forget that this virus can be potentially transmitted and spread through droplets or aerosols containing viral RNA when infected individuals cough, sneeze or speak, which are the main transmission routes of the pathogen. [75,82,85,88,89] Amount, size and distance of the particles can be relevant factors influencing the risk of transmission of the pathogen, meaning that individuals who are close to transmission sources are at higher risk, particularly health care professionals performing oral and facial surgeries, such as dentists, otolaryngologists and ophthalmologists, among others. In addition, small droplets (≤ 60 μm) can evaporate and become aerosols, reaching another host through the airflow and inhaled or settle onto the mucosas. [85] Nevertheless, it should be emphasized that one cannot establish a remote spread because there is no evidence supporting that SARS-CoV-2 can survive long in an outdoor environment. [82,85]
Aspects of Clinical Dental Practice Versus COVID-19
Because recent studies have shown the presence of SARS-CoV-2 in human saliva, dental professionals deserve special attention in relation to the risk of infection because they are directly exposed to the fluid. Therefore, dental professionals of all specialties may be vulnerable to this risk because they are in closer contact with patients while they examine their oral cavities.
The possibility of contact with asymptomatic patients is high, and consequently, strict biosafety measures must be taken. [90] Dental professionals are constantly exposed to aerosols that in turn may possibly be contaminated by the virus. Aerosols are both liquid and solid particles measuring less than 50 μm, and they can be suspended in the air for protracted periods of time, [91] whereas splatter is a mixture of air, water and/ or solid substances measuring from 50 μm to several millimeters in diameter. [92] In routine dental practice, dental drills cause the formation of aerosol and splatter commonly contaminated with bacteria, viruses, fungi and blood. [92,93]
In this context, some diseases are known to be spread by droplets or aerosols as occurs with pneumonic plague, tuberculosis, influenza, Legionnaires’ disease and SARS-CoV-2. [91]
Aerosol plays an important role in the spread of SARS-CoV-2 and can be considered a potential source of airborne contamination as previously reported in the other droplet-spread disease SARS. [91]
Experiments demonstrated that SARS-CoV-2 remained viable in aerosols for three hours as well as on plastic for up to 72 hours and stainless steel for up to 48 hours. [94]
The mechanism of inactivation of the new coronavirus by chemical agents is not yet well established. Human coronaviruses are known to remain viable on inanimate surfaces for up to nine days, but 0.1% sodium hypochlorite and 62% to 70% alcohol are effective in inactivating them after exposure for one minute. Therefore, the same is expected to happen to SARS-CoV-2. [95]
Reports have indicated that SARSCoV-2 has a higher transmissibility than SARS-CoV and MERS-CoV, meaning that a higher level of precaution and infection control regimen aimed at SARSCoV-2 is essential during this outbreak. [96]
In general, there is a tendency to associate dentists who perform restorative procedures with greater exposure to aerosols than those involved in other dental practices. On the other hand, the impact of the transmission of the disease on other dental practices, such as intraoral examination and biopsies typically performed by stomatologists and/or oral maxillofacial surgeons, is yet to be established. Nevertheless, simple contact with saliva is a potential risk for all dental professionals.
Oral and Maxillofacial Pathology Practice and Laboratory Routine
Oral and maxillofacial pathologists are constantly in contact with fragments of human tissue fixed in formalin. Formaldehyde 37% diluted in phosphatebuffered saline solution in a 1:10 ratio showed some effectiveness in inactivating SARS at appropriate temperatures, but virus samples can remain infectious even after three days of exposure to formalin. [97] Histopathological analysis of tissues from patients with COVID-19 has been performed with samples fixed in 10% buffered formalin. [98] It is suggested that formaldehyde fixation and paraffin inclusion can inactivate SARS-CoV-2.9
Since the WHO declared COVID-19 a pandemic, dental care has been considerably reduced worldwide. An oral health care center in Turin, Italy, recorded approximately 40 cases of squamous cell carcinoma in 2019. Dental emergency care is generally restricted to toothache. Thus, it is expected that there will be an increase in mortality rates due to oral carcinoma because of dental care restrictions, especially in the elderly population. [99] Consequently, there will be a decrease in the number of biopsy specimens sent to histopathology laboratories, reducing the flow of laboratory activities.
Some precautions must be taken by pathologists during the pandemic. The use of gloves, surgical masks, disposable gowns and caps is essential during macroscopic analysis and tissue processing. Histological slides should be handled with gloves, and contact with the face, nose or mouth should be avoided. During microscopic analysis, it is recommended to wear masks and glasses and to avoid sharing the microscope. After use, the microscope must be disinfected and covered with a plastic cover. Stationery materials should be handled with gloves and hands should be cleaned with soap and water after using the materials. [2]
Telemedicine has been widely used during the pandemic and is shown to be highly effective in the diagnosis and follow-up of oral lesions. [100] A letter to the editor published by Georgakopoulou cites cases where patients were being seen for the first and second times, including follow-up, for evaluation of oral lesions on the basis of photos. The diagnosis included erythema multiforme, herpetiform ulcers, temporomandibular joint pain, soft tissue reactive lesion, gingival cysts, erythematous candidiasis, oral hairy tongue, geographic tongue, oncological dental care, herpes zoster, secondary herpes, oral lichen planus, burning mouth syndrome and atopic cheilitis. [101] It can be said that telemedicine is an essential tool for oral medicine in times of pandemic, thus contributing to social distancing and ensuring patient care.
Final Remarks
The COVID-19 pandemic has shown an uncertain evolution in infected patients due to the influence of several factors. Our literature review compiled recent information on the new coronavirus by providing general data that were gradually tapered to more relevant ones for dental practice and finally stomatology and oral maxillofacial pathology.
Under the classic perspective of biosafety, the new coronavirus pandemic has a direct impact on all areas of health care including dentistry in terms of both clinical practice (i.e., direct care of patients) and laboratory routine procedures (i.e., oral pathologists performing histopathological analysis of tissue samples).
A rapid-spread disease results in several extrapulmonary manifestations, including possible oral repercussions that may be directly related to SARS-CoV-2 or result from the adverse effects of medications used as possible treatments of the disease. Under this perspective, the impairment of oral and maxillofacial structures by the SARS-CoV-2 infection needs to be better investigated by stomatologists and oral pathologists who should be aware of these possibilities during routine diagnostic process. Also, as more literature becomes available, the oral and mucosal effects from the SARS-CoV-2 virus can be separated from the potential drug interactions/reactions. Telemedicine should also be considered during diagnosis and follow-up of oral lesions.
It is also necessary to highlight the role played by saliva in three aspects, namely its diagnostic potential for detection of the virus, its predictive value regarding the possibility to follow the viral load in different moments during the course of the disease and its potential of transmission through droplets and bioaerosols.
This literature review of the pandemic caused by SARS-CoV-2 and its potential impact on the dental practice makes clear that in order to be prepared to deal with COVID-19, the dental professional, including stomatologists and oral pathologists, must stay current with new evidence and think critically about the possible direct and indirect implications that SARS-CoV-2 can have on oral and maxillofacial structures.
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THE CORRESPONDING AUTHOR, Tatiana Nayara Libório-Kimura, DDS, PhD, can be reached at tliborio@ufam.edu.br.
