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Abstract

Coronavirus disease 2019 (COVID-19), a viral disease declared a pandemic by the World Health Organization (WHO) in March 2020, has posed great changes to many sectors of society across the globe. Its virulence and rapid dissemination have forced the adoption of strict public health measures in most countries, which, collaterally, resulted in economic hardship.

This article is the first in a series of 3 that aims to contextualise the clinical impact of COVID-19 for the dental profession. It presents the epidemiological conditions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, its modes of transmission, incubation, and transmissibility period, signs and symptoms, immunity, immunological tests, and risk management in dental care.

Individuals in dental care settings are exposed to 3 potential sources of contamination with COVID-19: close interpersonal contacts (<1 m), contact with saliva, and aerosol-generating dental procedures. Thus, a risk management model is propsoed for the provision of dental care depending on the epidemiological setting, the patient’s characteristics, and the type of procedures performed in the office environment.

Although herd immunity seems difficult to achieve, a significant number of people has been infected throughout the first 9 months of the pandemic and vaccination has been implemented, which means that there will be a growing number of presumable “immune” individuals that might not require many precautions that differ from those before COVID-19.

In conclusion, dental care professionals may manage their risk by following the proposed model, which considers the recommendations by local and international health authorities, thus providing a safe environment for both professionals and patients.

Introduction

Since the beginning of this century, 3 novel coronaviruses (CoV) capable of infecting human beings have caused a significant number of infections, which led to the declaration of a public health emergency.

In November 2002, from the Guangdong province in China, came the first reports of patients with symptoms of a new disease that would come to be known as severe acute respiratory syndrome (SARS). A novel coronavirus responsible for this disease (SARS-CoV) was isolated in February 2003.1 The SARS epidemic affected 26 countries on 5 continents (Asia, Oceania, North America, Europe, and Africa), resulting in 8096 reported infections and 774 deaths, until the outbreak was declared contained in July 2003 by the World Health Organization (WHO).2,3 The case fatality rate associated with SARS was 9.6%.3 Since 2004, no new cases of SARS have been reported worldwide.4

Ten years later, in June 2012, Saudi Arabia reported the first cases of a new disease, later named Middle East respiratory syndrome (MERS). The pathogen responsible for this disease, a novel coronavirus (MERS-CoV), was isolated in September 2012.5,6 Since then, several outbreaks have been reported, with cases diagnosed in 27 countries. However, approximately 80% of cases were reported in Saudi Arabia, and the cases identified outside the Middle East have usually been associated with travellers infected in that region before returning to their original country.7,8 As of January 2020, 2519 cases of MERS had been confirmed, resulting in 866 deaths, which corresponds to a case fatality rate of 37.1%.9

In December 2019, the city of Wuhan, in the province of Hubei in China, became the epicentre of an outbreak of pneumonia of unknown aetiology.101112 On January 7, 2020, a novel virus was isolated from patients with that disease, and the International Committee on Taxonomy of Viruses named it “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2) in February. In March, WHO named the disease the coronavirus disease 2019 (COVID-19).13,14 Initially, the SARS-CoV-2 epidemic remained limited to China, with most cases being reported in the province of Hubei, and only isolated cases being detected in neighbouring countries, such as Thailand, Japan, and the Republic of Korea.15 However, in the following months, the disease spread worldwide. On January 23, the United States reported its first case.16 On January 25, the first cases were reported in Australia and France—presumably, the first European country to be affected by this disease.17 On February 15, WHO reported the first case on the African continent (in Egypt).18 On February 27, the first case of this novel coronavirus appeared in South America (in Brazil).19 During March 2020, with the reported number of new cases decreasing in China, the epicentre of the epidemic shifted to Europe, with the largest outbreaks of cases first in Italy and then in Spain. On March 12, with the disease reported in more than 100 countries, COVID-19 was officially declared a pandemic by WHO.20 During April, May, and June, the epicentre of the epidemic shifted once again, this time to the Americas, mainly the United States, Brazil, and Chile. The following months, some countries that had the epidemic under control faced new foci or the second wave with a significant increase in the number of deaths This trend resulted in making COVID-19 the leading cause of death in some countries.21

As of December 27, 2020, a total 79,231,893 cases of COVID-19 had been reported worldwide, of which 1,754,574 resulted in death, corresponding to a case fatality rate (CFR in percentage; number of reported deaths/number of reported cases) of 2.2%.22 However, slight variations in the reported CFR in different parts of the world have been observed: Africa 2.2%; Americas 2.4%; Eastern Mediterranean 2.5%; Europe 2.2%; Southeast Asia 1.5%; and Western Pacific 1.8%.22 Such differences seem to be related to geographic and social differences of the countries in those regions, including the methods used for counting cases, the mean age of the population, the intensity of the outbreak, the type of containment measures adopted, and how soon those measures were adopted.23 It has been found that patients older than 65 years of age have a higher risk of death if they become infected.24 The COVID-19 CFR has also been higher in individuals with a previous chronic disease, which corresponds to more than half of the countries reaching 90% of the cases of infection.252627 Most COVID-19 confirmed cases have been in patients older than 30 years age, with more than 90% being older than 45 years of age.28,29 Determining the severity of COVID-19 is critical for implementing mitigation strategies and planning for health care needs as the pandemic evolves. However, the CFR is a poor measure of the mortality risk because a large number of people are asymptomatic or present with mild symptoms, and testing has not been performed on the entire population.30 A better way to estimate the mortality risk is the infection fatality rate (IFR in percentage; number of deaths from COVID-19/total number of infected individuals). Published research data on COVID-19 showed overall IFR converging around 0.2%-1.6% in the first months of the pandemic.31 Moreover, the estimated age-specific IFR is low for children and younger adults (eg, 0.002% at age 10 and 0.01% at age 25) and increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85.323334

Due to its infection rate and lethality, the COVID-19 pandemic has become one of the greatest public health challenges of this century because no treatment or vaccine were initially available. The main problem has been the rate of COVID-19 patients that require admission in intensive care units (ICUs) and, particularly, the use of mechanical ventilation because some health care services might not be able to meet the demand, which may ultimately increase the percentage of infected individuals who die, raising the IFR. Thus, infection control measures are essential to prevent viral propagation and help control the epidemic.35 With the COVID-19 pandemic’s geographic expression progressively widening across the globe, several countries have implemented strict measures to reduce interpersonal COVID-19 transmission. In the health sector, particularly in the provision of dental care, the implementation of additional measures to contain the possible transmission of the disease was considered essential.36

Currently, people suspected of having COVID-19 present with certain symptoms including acute respiratory infection (sudden onset of fever, dry cough, or respiratory distress) without other aetiology that explains the clinical signs and symptoms and with history of travelling or living in areas with active community transmission in the 14 days before symptoms onset; acute respiratory infection and contact with a person with a confirmed or probable case of COVID-19 in the 14 days prior to the onset of symptoms; or severe acute respiratory infection, requiring hospitalisation, without other aetiology that could explain the clinical presentation.37

This article is the first of a series of 3. With these 3, we aim to contextualise the virus SARS-CoV-2 and the disease COVID-19 for the dental profession, focusing on risk management in dental care, COVID-19’s repercussion in dental settings, personal protective equipment (PPE) selection and proper use, and measures to be applied in the dental office.

This first article aims to contextualise the clinical impact of the disease for the dental profession. It presents the epidemiological conditions of COVID-19, namely, its modes of transmission, incubation and transmissibility period, signs and symptoms, immunity, immunological tests, and risk management when dental care is provided.

Epidemiology

Modes of transmission

The origin of the virus responsible for COVID-19, SARS-CoV-2, is still being debated and investigated. Despite some controversy and although not yet fully clarified, the comparative analysis of genomic data suggests that the outbreak may have begun with a zoonotic animal-to-human transmission, with a pangolin that was infected by a bat in a market in Wuhan and later infecting a human being.38 It was then followed by human-to-human transmission, which led to its spread, starting in the city of Wuhan in China.39

SARS-CoV-2 is highly contagious and is transmitted via respiratory droplets, by direct contact with infected people, or by contact with contaminated surfaces and objects.40 The respiratory droplets expelled from the nose or mouth when an infected individual coughs, sneezes, or speaks may come in contact with the oral, nasal, or conjunctival mucosae of an individual standing nearby, thus resulting in transmission of the disease.40,41 Contamination may also occur indirectly by hand contact with contaminated surfaces followed by hands in contact with the face.40,42 Research has shown that in an external environment, such as inert dry surfaces, SARS-CoV-2 might survive up to 72 hours on plastic and stainless steel, 24 hours on paper or cardboard, and less than 4 hours on copper surfaces, depending on the temperature and humidity. In watery environments, the virus might survive several days.43

Clinical and virologic studies suggest that the viral load is particularly high in the superior respiratory tract, nose, and throat in the first 3 days after the onset of symptoms.44,45 However, the virus has also been found in several body fluids, including faeces, and, thus, the risk of faecal-oral transmission cannot be dismissed.42,464748

The viral load needed for SARS-CoV-2 transmission is approximately 1000 viral particles per minute (vp/min). As a reference, when breathing, approximately 20 vp/min are expelled; when talking, 200 vp/min; and when coughing or sneezing, 200 million vp /min. The transmission risk is low in outside spaces and surfaces.49

It is known that the SARS-CoV-2 viral load peaks approximately at symptom onset, with a viral load similar to that of influenza.50 Conversely, SARS-CoV and MERS-CoV peak at around 10 days or during the second week after symptom onset. This viral load profile behaviour of SARS-CoV-2 suggests that it can be easily transmissible at an early stage of infection.51 Older people may have higher viral loads.50

It has been suggested that, although there is no clear evidence that SARS-CoV-2 can be transmitted to humans through pet cats and dogs, these animals can be contaminated with COVID-19 by their owners.52,53 A different SARS-CoV-2 strain has also been reported in mink on farms in multiple countries.54 Usually asymptomatic or with slight respiratory and digestive symptoms, pets may act as asymptomatic dispersers of SARS-CoV-2.52,53

SARS-CoV-2 presents as a sphere of 0.06 to 0.14 µm in diameter and may be found in saliva droplets, which can remain in the air for long periods.55,56 Therefore, airborne transmission is a possibility, mainly in closed areas, in some aerosol-generating procedures (AGP), such as those occurring in tracheal intubation, bronchoscopy, noninvasive ventilation, tracheotomy, manual ventilation prior to intubation, and cardiopulmonary resuscitation, among others.57,58 There is no evidence of SARS-CoV-2 transmission through AGP in dental care environments, but it remains a possibility.59

Since SARS-CoV-2 is an RNA virus, this type of virus tends to mutate more easily. Three different strains were initially detected in different continents: A in Australia and the United States; B in China and Europe; and C in Europe via Singapore. Another mutation (D614G) emerged in Europe in February and became the dominant form of the virus throughout the world.60 Since then, different strains have developed without changing its virulence. In November, new strains were found in the United Kingdom and in South Africa. The UK strain seems to spread 70% faster, which may lead to faster virus spread in a population.61 This strain presents 17 potentially important mutations, including changes in the spike protein.61

Incubation period and transmission

The mean incubation period for COVID-19, from exposure to the virus to the onset of symptoms, is 5 to 6 days on average, although it may be as short as 2 days and as long as 14 days.626364 The high viral load found mainly in the first 3 days after the onset of symptoms seems to explain why COVID-19 is transmitted mostly by patients who are symptomatic.44,45 Nevertheless, considering that some individuals may test positive for COVID-19 a few days before developing symptoms, and based on some clinical reports, transmission in a presymptomatic stage (the incubation period) is also a possibility.39,65666768697071 Lastly, although there are reports of truly asymptomatic cases confirmed by laboratory tests, there is no evidence of asymptomatic transmission (when the infected person has no symptoms throughout the course of the disease)72 because that is difficult to quantify. However, this does not exclude the risk of COVID-19 transmission by asymptomatic carriers that may be 3-25 times lower than for those with symptoms.63,69,73,74

As in most infections, clinical signs and symptoms may be mild or absent (asymptomatic carrier), and patients who have been exposed are advised to remain under medical observation and quarantine or isolation for at least 14 days.

Clinical signs and symptoms

The clinical signs and symptoms of COVID-19 vary widely, from asymptomatic or subsymptomatic presentations to a flu-like syndrome43 to severe respiratory insufficiency requiring mechanical ventilation in ICUs, which may ultimately lead to death.75 The most common signs and symptoms are fever, dry cough, and tiredness. Less common symptoms, such as aches and pains (headache and muscular pain), sore throat, expectoration, rhinorrhoea, haemoptysis, anosmia (loss of the sense of smell), ageusia (loss of taste), diarrhoea, and vomiting, may also be present.76

Of those, anosmia and ageusia might cause dental patients to visit to the dentist and provide to the dentist a reason to suspect COVID-19.

In more complex situations, the clinical presentation may be moderate to severe disease with pneumonia, dyspnoea, increased respiratory rate, and decreased blood oxygen saturation; or critical disease with respiratory insufficiency, acute cardiac injury, septic shock, and multiple organ failure, which more frequently results in death.26 These more severe cases seem to be associated with massive inflammatory reactions in the endothelium of several organs, including the lungs and the heart.777879 On the other hand, the high incidence of thromboembolic events suggests that COVID-19-induced coagulopathy plays an important role in the disease outcome.798081 Patients infected with coronaviruses associated with severe respiratory disease, such as COVID-19, have shown inappropriate activation of the coagulation cascade and subsequent formation of systemic or intra-alveolar fibrin clots, which may result from an attempt of the prothrombotic response to prevent diffuse alveolar haemorrhage that instead causes clot formation, negatively affecting recovery and survival.82,83

Platelet and fibrin thrombi found in small pulmonary vessels of patients who died from this disease may explain the severe hypoxemia that is characteristic of the acute respiratory distress syndrome associated with the more severe forms of COVID-19.78,80 Most patients seem to develop SARS-CoV-2-induced pulmonary changes, with diffuse alveolar damage, leading to acute respiratory insufficiency.84 Pneumonia, which can be combined with pulmonary embolism/emboli, have been identified as the main cause of death.81,85

Additionally, it is clear that bacterial superinfections are common in patients suffering from a severe case of COVID-19.86 Poor oral hygiene should be considered a risk to COVID-19 complications in patients with diabetes, hypertension, or cardiovascular disease because they are more prone to have biofilms with a higher percentage of pathogens.86 In these particular cases, oral hygiene should be improved during a COVID-19 infection to reduce the bacterial load in the mouth and the risk of a bacterial superinfection.86

Although the combination of the previously described signs and symptoms with lung imaging may suggest COVID-19 infection, the final diagnosis depends on the confirmation by a laboratory test.87 Samples obtained via an oral or nasal swab, as well as from the trachea and nasopharynx, pulmonary tissue, saliva, expectoration, faeces, and blood can be isolated and used for detection of COVID-19 using molecular diagnostic techniques.

Immunity

The nature and duration of potential immunity after contact with the virus remains unknown. Advancing scientific knowledge on this particular aspect of infection may lead to significant changes in the management of the disease within a community. Herd immunity to SARS-CoV-2, requiring more than 60% of the population to have been infected, is believed to be achievable but depends directly on whether a robust immune response is generated after contact with the virus. At present, it is estimated that only 12% of the world population has come in contact with the virus, but it can be predicted that this is 6.2 times larger than the estimated rate,89 which is far below the 60% target.

A potential solution for the pandemic is the development and deployment of vaccines. Until now the average time to develop a vaccine was 10 years, and the fastest was the Ebola vaccine that was produced in 5 years. Several companies started the development of scientific tests to produce a vaccine within an acceptable time frame.90 Due to great investments and compromise between companies, governments and regulatory agencies, 5 vaccines became available in less than a year.

The first vaccines to be administered in the United States and Europe were the Pfizer/BioNTech and Moderna vaccines. Both are lipid nanoparticle-formulated, nucleoside-modified RNA vaccines that encode the prefusion stabilised SARS-CoV-2 full-length spike protein with similar vaccine efficacy (around 95%) and low  incidence of serious adverse events.91,92 Spike proteins are thus produced by host cells, which mount an immune response to those proteins.

Vaccines using a viral vector are also available, such as AstraZeneca/Oxford, the Chinese Sinovac, and the Russian Sputnik V vaccines, in which modified viruses deliver the genetic code for antigens to stimulate the body to develop immunity. Overall efficacy of the Oxford vaccine was reported at 70.4% (62.1% in participants who received 2 standard doses and 90.0% in participants who received a low dose followed by a standard dose) with an acceptable safety profile.93

Vaccination has started in several countries, with priority to the high-risk groups and is expected to continue throughout the year.

Advances in hospital-based COVID-19 care and therapeutic agents authorised by national agencies such as monoclonal antibodies Remdesivir and dexamethasone treatments seem to show effectivity for SARS-CoV-2, although some variants appear to be more resistant to monoclonal antibody treatment.94,95 However, at this moment, prevention is still the main approach to controlling the pandemic.

Tests

Two types of tests are available to detect viral infections: reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays and serological immunoassays that detect viral-specific antibodies (immunoglobulin M [IgM] and immunoglobulin G [IgG]) or viral antigens, typically part of the surface protein.

Presently, RT-qPCR and antigen tests are used for ongoing infection detection for SARS-CoV-2. These tests has been essential to screen and identify people infected with COVID-19. RT-qPCR diagnostic tests can be quick, providing results after 1-8 hours and WHO’s interim guidelines indicates its use to confirm suspected cases of COVID-19.96,97 Nevertheless, due to the incubation period, the technique used to obtain samples, their transportation, and the analysis method, these tests have relatively low sensitivity, from 60% to 80% and may result in many false-negative results.98

In situations where RT-qPCR diagnostic tests are unavailable or time constrains are a problem, antigen-detecting rapid diagnostic tests (Ag-RDT) can be used in the diagnosis of SARS CoV-2. Antigen-detecting rapid diagnostic tests compared to a RT-qPCR appears to be highly variable, ranging from 0%-94% but specificity is consistently reported to be high (>97%).99,100

Immunological methods, such as serologic tests (to identify IgG and IgM), may be used to detect whether an individual has been exposed to SARS-CoV-2.87 These tests required more time to be developed because they require knowledge of the structure of the proteins that form the viral coat. Highly specific serological tests sensitive for SARS-CoV-2 antibodies, with a precision higher than 95%, are currently available using several SARS-CoV-2 proteins.101 The clinical sensitivity of the serological tests for anti-SARS-CoV-2 IgM and IgG antibodies, when used in combination, is 98.5%, with a clinical specificity of 98.7%. A positive result for IgM may reflect recent exposure to the virus, 3 to 10 days after the onset of symptoms, whereas a positive result for IgG may represent an exposure 10 to 20 days after onset of symptoms. During the convalescence stage, the IgG antibody may increase approximately 4-fold compared with the acute stage.64,98,102 The SARS-CoV-2 spike protein (S protein), which makes the serological tests more unique and lowers the odds of cross-reactivity, is used for differentiation from other coronaviruses. However, assessment of acquired immunity is further complicated by lack of clarity related to cross-reactivity to IgG directed towards other coronaviruses.97,103104105106

The use of saliva for the diagnosis of COVID-19 has been a worldwide focus of interest. This fact is related to the sensitivity of the salivary sample being similar to that of respiratory samples. On the other hand, the ease of collecting allows the risk of viral transmission for health professionals to be reduced and can be self-collected without the need for trained people, saving medical human resources in the context of pandemics.107,108 Although RT-qPCR represents the reference standard for molecular diagnosis in salivary samples, the time spent makes it difficult to use when a population screening program is intended to be carried out. However, rapid salivary antigen tests can be used in pandemic outbreak containment programs. These tests have a main application outside the hospital context due to their ease of use and speed in providing results (30-60 minutes), requiring no specialists.

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