Covid-19 outbreak and Oral Health Concerns – A Systematic Review


 Background:The aim of this systematic review is to shed light on practical implications of Covid-19 pandemic for the profession of dentistry. It examines the current literature and dental guidelines on Covid-19 in a systematic manner.Methods:A sequential systematic literature search was conducted on Pubmed, Medline, CINAHL, Scopus, Google scholar, Embase of Web of Science. The search results yielded the following results-Covid-19 (n=5171), Novel corona virus (n=63), Covid- 19 and dentistry (n=46), Covid-19 and oral health (n=41) Novel Corona virus and Dentistry (n=0), dental health and Novel Coronavirus (n=26), and dental practice and Novel Coronavirus (n=6)Results:The final review included 13 articles after elimination of other articles based on inclusion and exclusion criteria. Original articles and systematic reviews addressing 2019-nCoV and dentistry were entitled for inclusion, case reports, case series, correspondences, editorials were not included. Bias risk assessment was assessed using the Newcastle-Ottawa Scale (NOS)Conclusion:Covid-19 pandemic is an existential crisis for the profession of dentistry and requires a complete rethink about many aspects of the profession due to the nature of dental work. Evidence based research and multi-sectorial collaboration is required to make the profession safe again, both for the patient and dental team.

population 4 . Until any effective strategies such as vaccine for camels against MERS-CoV is available, sporadic cases of human MERS-CoV will continue to appear 4 . In December 2019, pneumonia of unknown origin was reported in Wuhan, a town in Eastern China. The World Health Organization o ce in China provided the rst reports of a new virus of unknown origin after a number of pneumonia cases and in conjunction with this the rst cluster of cases were reported in people associated with the South China Seafood market in Wuhan. The surveillance system as it was established during the SARS-CoV outbreak was implemented and the patient's throat swabs were sent to the laboratories for etiological analysis 5 . The causative agent was identi ed by Chinese Centre of Disease Control and Prevention and the Wuhan seafood market was shut down immediately; but by then this virus had already begun to spread beyond the market itself 6 . Initially the virus was named as 2019 novel coronavirus; later it was named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as suggested by Coronavirus Study Group (CSG) of the International Committee on Taxonomy of viruses 7 . On January 30, 2020, the World Health Organization (WHO) declared the rapid spread of SARS-CoV-2 and its associated Coronavirus Disease 2019  as public health emergency of international concern with overall case-fatality rate of 3.4% 8,9 . According to WHO situation report of April 16, 2020 there have been approximately 2 million reported cases and 130,000 deaths globally, and the number of reported cases continue to increase 8 .
SARS-CoV-2 is a β-coronavirus that is encapsulated with a non-segmented positive-sense RNA virus that can be transferred from person to person 10 . Based on the ndings of virus genome sequencing and genetic research, bat was primarily suspected of being the host. In fact, similarity of protein sequences and phylogenetic analysis have shown that identical receptor residues have been found in several animals, offering new resources for potential intermediate hosts, such as turtles, pangolins and snakes 9,10 . Here we performed dynamical simulations on a model that can closely capture the geometric features of the spike protein within the membrane wall of the virus and the presence of a micro domain within the membrane. The molecular docking studies were carried out using Schrödinger small-molecule drug discovery suite 2019-4. It was prepared for molecular docking studies using protein preparation wizard of Schrodinger 2019-4 using OPLS-3e force eld at pH 7.40 ± 0.02 and the other default settings. The entry of SARS-CoV-2 inside humans is lungs whose pH is 7. 38 -7.42. So, the protein was prepared at pH, 7.40 ± 0.02. The SARS-CoV-2 spike protein binds with ACE-2 of lungs. In the crystal structure, 6LZG, chain A is hACE-2 protein and chain B is spike protein. The fragments were docked into protein and ligand sites using GLIDE module in Schrodinger and followed 'Standard precision' docking protocol with default settings. This model is a result of computational feasibility (Fig 1) mimicked by attractive interactions (ε 0 ) considering diffusivity, uidity and rigidity as bilayers are obtained with widths of 5 nm. The electrostatic interaction between proteins and membrane polar head groups show no repulsive component. The notable feature is the subunit spike at the polybasic site at the junction of S1 and S2. There are proline turns anking the cleavage site which is very unique to SARS-CoV-2. Given the known genetic variation and depth of the spike, there is enhancement of MERS-like coronaviruses infection transferring from bats to human cells 11 . Studies are currently being conducted in our lab to assist scientists who have been doing research relevant to drug discovery and/or development; also to frame their research report in a way that appropriately places their ndings within the drug discovery and development process.
Scienti c studies have shown that there are two main routes of transmission of  i.e. direct (personto-person touch or inhalation of short-range respiratory droplets) and indirect (airborne and fomitemediated) 12,14 . Individuals may acquire indirect infection by getting in touch with the contaminated surfaces and then contacting their oral, nasal or ocular mucosal surfaces 13 . The infection is spread by large droplets formed by symptomatic patients while coughing and sneezing, which may also occur in infected asymptomatic individuals 14,15 . Some researchers from the United States and China have reported possible faecal-oral transmission of SARS-CoV-2, while vertical transmission from mother to infant is still being investigated. The most commonly cited clinical symptoms of Covid-19 are raised body temperature, dry cough, malaise, and dyspnoea 15 . Computerized Tomography (CT) scan ndings included pneumonia with anomalous ndings in all cases. In the less common ndings, cephalgia, diarrhoea, vomiting, sore throat, and production of sputum have been reported 10,16 . Although all demographics of global population are at-risk for Covid-19 infection, some groups including older adults (over 65 years of age) or people with co-morbidities (namely hypertension, diabetes, cardiovascular disease, lung cancer, people taking immunosuppressant drugs, and chronic obstructive pulmonary disease) can manifest severe forms of disease and associated complications, which may lead to death 17 . Healthcare workers and patients hospitalized for other reasons are at higher risk for Covid-19 due to possibility of frequent close contact with symptomatic and/or asymptomatic individuals infected with Covid-19 17 .
The pandemic initially began in China which endured much of the infections of . Over the passage of time cases in China have waned down, but the disease has continued to intensify in other parts of the world 17 . Currently, USA with almost 1,645,353 cases and 97,655 deaths, Spain with 281,904 cases and 28,628 deaths, and Italy with 228,658 cases and 32,616 deaths are the epicentre for this epidemic 18 . The current spread of coronavirus continues to grow, affecting almost all the countries with many fatalities. The World Health Organization declared SARS-CoV-2 outbreak a worldwide pandemic on March, 11th 2020. Not only has the pandemic impacted the physical well-being of the entire planet, but it has led to global economic decline which has in uenced many industries in the rst half of 2020 and dentistry is one of them 19 . Similarly, the dental fraternity is experiencing a drastic transition and will continue to do so over the coming weeks and months as a consequence of the of the SARS-CoV-2 outbreak 20 . The consequences are far-reaching and unpredictable, particularly for the dental community and for patients seeking dental care. Results from a recent study showed that aerosols containing SARS-CoV-2 remain infectious for up to 3 hours in con ned spaces, 4 hours on copper, 24 hours on cardboard, and up to 3 days on stainless steel and plastic (Fig 2). Since use of ultrasonic scaler, triple syringe, dental hand piece, and other high-speed driven instruments during dental treatment can generate tremendous amount of aerosols, putting dental practitioner's dental surgery assistants and their patients at high risk for contracting Covid-19 21 . There have been many recommendations in the United States and elsewhere to cease non-essential dental procedures and restrict treatment to emergency care 19,22 .
Dental practitioners are facing uncertainty and are being forced to rely on general information on Covid-19 transmission routes and other guidelines being followed by general frontline health staff to protect themselves and their patients 22 . Dental practice serves as a contagion point and a vector for  outbreaks in the population if appropriate protocols are not followed. With its outbreak, Covid-19 has raised the bar for delivering high-quality dental care around the globe. This scoping review is an effort to review all the relevant literate published so far on dental aspects of  in order to serve as point of synthesis for future recommendations and guidelines for dental practices in these troubling times.

Methods
There were two independent reviewers (Drs. SM & ZA) who screened the titles and abstracts of all the identi ed studies to determine the relevance meeting the pre-determined inclusion criteria ( Table 1). The authors screened PubMed, Scopus, Web of Science, Embase, CINAHL, Medline and Google scholar databases after December 2019 till April 2020 for appropriate articles addressing the question under review. The researchers reviewed all the articles after reading the abstracts of the relevant publications. Full text was screened if there were insu cient data to make clear decision based on abstracts. A structured and logical approach to literature search was used to identify the relevant papers that investigated Covid-19 and its dental implications. Reference lists of original studies were manually searched to identify any articles that could have been missed during the initial search, keeping the inclusion criteria in mind. Any disagreements regarding study selection were resolved via discussion. (Table 1 of inclusion and exclusion criteria).  Fig 3) 23 . The search parameters used for inclusion criteria were: articles in English language, at least one keyword corresponding to the above entries in the title/abstract and study based on the evaluation of research articles (Table 3). Original articles and systematic reviews addressing 2019-nCoV and dentistry were entitled for inclusion, case reports, case series, correspondences, editorials were not included. All keyword searches, title and abstract screening, as well as selection of studies, were carried out independently by two investigators (Drs. SM/RA). Articles published before December 2019 were not included as Novel Coronavirus only emerged into the scienti c conscience and mainstream after December 2019. Furthermore, online OPD reports/patient-physician testimonials and other online materials was skimmed for other relevant material (PRISMA owchart, Fig 3) 23 . Only articles published in peer reviewed journals were selected for the nal review. As Novel coronavirus is a new disease, the data on dental aspects of the virus was extremely limited, but we were able to gather a sizeable number of studies that could serve as the initial groundwork for providing guidelines to the dental community in these uncertain times. Studies or other materials published before December 2019 were not included in our analysis. Therefore, the selected articles were published between January 2020 and April 2020. Papers not published in peer-reviewed journals were excluded, as well as studies not matching the inclusion criteria. Articles published in any language other than English were discarded as none of the author is uent in other languages.
Risk of bias assessment Assessment of the risk of bias of the reviewed studies is a fundamental aspect of conducting a systematic review. Bias risk assessment in the reviewed studies was examined using the New-Castle-Ottawa scale (NOS) 24 . The Newcastle-Ottawa scale is a tool for quality assessment ranking studies by assigning them stars*. A modi ed version of the Newcastle-Ottawa scale was used in the study which used a 10-star rating instead of the usual nine. The stars are rank 3 key domains of the study being assessed i.e. (selection, comparability & outcome). The NOS can be interchanged with the commonly used AHRQ (Agency for healthcare research and quality standard assessment). The more stars, the lesser the risk of bias in the studies included. The study is rated as poor (0-4*), fair (5-6*) or good (7-9*). The results of the assessment are displayed in this article (Table 3).

Statistical Analysis
For reliability evaluation, the inter-observer reproducibility and the intra-observer reproducibility were evaluated using weighted Kappa (κ w ) statistic.

Results
A summary of characteristics of the studies is presented in Table 4.  23 . Data base and manual search yielded 5,353 articles in total. 4913 Articles remained after elimination of duplicate records. Furthermore 4786 articles were removed after examining abstracts, following which 127 remained for full text assessment. The nal systematic review included 13 studies after excluding 114 articles due to lack of relevance in outcome to our stated research question, letter to editor and articles in languages other than English were also eliminated. 6 original articles and 7 review articles were selected for the nal review. Four of the studies were cross sectional in nature 28  The state of nonemergency dental care, emergency dental facilities, Online consultation and regional spread of hospitals were evaluated during  All 48 public tertiary dental hospitals discontinued regular non-emergency dental care and were offering emergency dental facilities only. The penetration rate of teleconsultation in the eastern area was considerably higher than in the central and western regions.

Discussion
The uncertainty and chaos caused by the covid-19 pandemic raises many concerns for dental profession regarding practice safety and evidence-based guidelines. A wide array of recommendations available through scienti c publications related to covid-19 and dental practice management, makes the task of presenting the most relevant and up to date literature more important than ever. The aim of this scoping review was to capture, document, and demonstrate all the relevant literature published so far on dental aspects of Covid-19 in order to serve as point for future recommendations and evidence-based guidelines for dental practices in this challenging time.
Considering that dental professionals are at higher risk of exposure to , infection control has been discussed intensively in the literature 25, 26, 27, 30, 31, and 34 . Ge Z et al argued that aerosol-generating dental procedures for suspected/con rmed Covid-19 patients have a particularly higher risk of infection transmission 27 . To achieve optimal infection control, a better understanding of the chain of infection is crucial for the control and prevention of any infectious disease 38 . The chain of infection requires a pathogen (virus or bacteria), natural reservoir (human or animal) to reside and multiply, which then leaves host through portal of exit, and enters into a susceptible host through portal of entry using some mode of transmission 38 . Interrupting chain of infection anywhere along the chain will stop the spread of infection 38 . The standard infection control provisions in dentistry can potentially serve as rst line of defence for many dental professionals. However, considering highly contagious nature of SARS-Cov-2, extra protective measures should be adopted to prevent the transmission of Covid-19 disease 25 .
We have identi ed 4 crucial phases which can be adopted to break the chain of transmission: (i) protocols for patient triage before treatment, (ii) patient evaluation upon arrival, (iii) during treatment, and (iv) after treatment. With many countries and different states in the US limiting dental procedures to emergency care during Covid-19 pandemic, it is important to establish the real need of emergency treatment 29,31,34 . We found six out of the thirteen articles across different geographic locations (including China, USA, Italy) and practice settings, which implemented telephone triage using questionnaire to evaluate potential risk of SARS-Cov-2 transmission and type of dental care needed 25,26,27,31,32,34 . Emergency dental care for patients reporting symptoms of Covid-19, contact with Covid-19 infected individuals, or travel to highly epidemic regions in the past 14 days should be postponed and pharmacologic management of pain or infection should be considered 31 . When the patient arrives at the clinic, the same questionnaire should be repeated and body temperature should be documented using non-contact thermometer 25,31,34 . Patients with temperature > 100.4 F or 38 o C should be postponed if possible or performed in an Airborne Infection Isolation Rooms (AIIRs) or negative pressure rooms 27,31,32 . AIIRs are highly recommended for aerosol generating procedures. These are single patient isolated room with minimum 6 air changes per hour 27,39 .
Air from these rooms is exhausted outside, away from areas of human tra c or gatherings or ltered through high e ciency particulate air (HEPA) lter, with negative pressure monitoring system held in place 27,39 . AIIRs or negative pressure rooms have been recommended and utilized in the management of corpses with suspected/con rmed Covid-19 patient's 40 . Waste management and psychological impact of Covid-19 on dental work force was another theme explored extensively in the literature.
Hand disinfection for patients, removal of shared objects (toys, drinks, magazines, etc.), 6 feet social distancing, limiting number of patients and use of mechanical or natural ventilation in the waiting area has been suggested to minimize risk of disease transmission to other patients and staff 27,31,34 . If patient cannot go directly to the treatment area, then standard mask and a pair of gloves should be provided while waiting 31,41 . Ge Z et al suggested posting cough etiquette instructions at entrances and waiting area to promote respiratory hygiene 27 . When preparing patient for the treatment, it has been suggested that preprocedural mouth rinse with an oxidizing agent such as 1% hydrogen peroxide or 0.2% povidone iodine for 1 minute should reduce the viral load in aerosols 25,31,34,42 . Several studies reported that a common preprocedural mouth rinse, chlorhexidine may not be effective against Sars-Cov-2, because there is lack of evidence or systemic data and virus is susceptible to oxidation 25,27,34 . In addition, use of rubber dam and high-volume evacuation/suction (HVE) during aerosol generating restorative procedures can reduce airborne and surface contamination 25,31,32,34 . Use of less expensive high-volume evacuator (HVE) or expensive high e ciency particulate arrestor (HEPA) lters, if held within 6 -15 mm of aerosol generating tip can clean up to 90% and 99.99% contaminated air, respectively 27 . A rubber dam should be used where possible, which can potentially eliminate all sources of aerosol contamination from blood or saliva by blocking the throat and soft tissue area, except the tooth/teeth undergoing treatment 43 . An in-vitro trial conducted by Samaranayake et al found 70% reduction in aerosol with use of rubber dam during conservative pedodontic procedures 44 . Peng et al recommends use of Carisolv, a minimally invasive chemo-mechanical removal of carious dentine and hand scaler for periodontal procedures where rubber dam is not feasible 25 . Finally, the effectiveness of rubber dam as an isolation barrier is merely dependent on the placement skills of the provider and its' technique sensitivity 45 . Peng et al emphasized use of dental hand piece with anti-retraction/anti-re ux valve to prevent aspiration of contaminated bodily uids into the tubes of hand-piece or dental unit and subsequent cross-infection 25 . Although there is limited evidence on effectiveness of anti-retraction valve for eliminating risk of cross-infection, its use has been suggested as an additional preventive measure to reduce cross-contamination 46 .
There has been much debate about choice of ltering face-piece (FFP), level 1 vs level 2 vs level 3 for aerosol and non-aerosol generating dental procedures. Some authors suggest wearing FFP1/standard surgical mask for non-aerosol generating procedures and FFP2/N95 or higher for aerosol generating procedures 25,27 while others suggest FFP2/N95 for all procedures for both clinical and non-clinical staff 31, 34, and 35 . A systematic review of clinical trials assessing effectiveness of N95 respirators in comparison to standard surgical mask found no additional protection in preventing in uenza 45 . The evidence from SARS-CoV research suggests that small infectious particles of up to 3 μm remain airborne inde nitely in an isolated room 48 . Patients and dental professionals can be exposed via inhalation of sustained small airborne infectious particles, upon entering the room used to perform airborne generating procedures when minimal protection of standard surgical mask is used 25,35 . Therefore, considering highly infectious nature of Sars-Cov-2 compared to in uenza, we recommend use of FFP2/N95 for both clinical and dental assistants and all dental procedures. Every patient should be considered potentially contagious. Hand hygiene has been extensively emphasized as key factor in preventing cross-contamination, a two-beforeand-three-after hand hygiene guideline recommended by CDC and WHO has been suggested 25, 27, 28, 31, and 34 . Dental professionals should disinfect their hands with soap or 70 -90 % alcohol before patient examination, before dental procedures, after touching the patient, after touching patient's contaminated surrounding or instruments, and after bodily uid exposure 25,27 . Eye protection with safety glasses and face shield has been suggested, which can be disinfected using 70% alcohol 25,34 . Alharbi et al recommends use of extra-oral radiographs such as orthopantomogram, and cone beam computer tomography over intraoral to prevent gag and excessive salivation 32 . Overall, a layering approach including head covers, long-sleeved water-resistant gowns, shoe cover, level 2 FFP, and eye protection has been proposed for both clinical and dental assistant's staff to signi cantly break the chain of infection 25,27,31,34 .
After the procedure is complete, disinfection of the treatment room and waiting area including doorknobs, chairs, desks, restrooms, and elevators between patients has been suggested to break the chain of transmission 27,31,34 . Hospital-grade disinfectants including quaternary ammonium-based, phenol-based, and alcohol-based products such as 0.1% sodium hypochlorite or 70% isopropyl alcohol has shown evidence to be effective against coronaviruses 49,50 . Wei et al indicate that airborne aerosol particles of less than 50 μm can take up to 30 minutes to settle on the oor, while particles less than 3 μm may remain airborne inde nitely 48 . It is also important to note that, research from Wuhan hospitals related to bio aerosol transmission of Covid-19 reveals high load of virus droplets on the oor and surfaces, indicating likelihood of fomite mediated, and that the dried large droplets may become airborne again 53,54 . Thus, we recommend ventilating room for 30 minutes before disinfection or using high e ciency or HEPA lter air puri er, and possibly UVC light for small airborne particle 51,52 . It is important to clean/mop oor between patients especially after aerosol generating procedures and wearing shoe covers, to effectively disinfect treatment and waiting area 25,34,53,54 . Dental providers need to consider best practices approach to create clean and safe environment for their staff and patients and to minimize risk of disease transmission. Notable consideration should be given to staff training, education, revision & reinforcement of infection control protocols. We suggest creating separate clinical and non-clinical area.
Waste management and psychological impact of Covid-19 on dental work force was another theme explored extensively in the literature. Treatment and disposal of medical waste pose indirect health risk due to environmental contamination, therefore it should be disposed-off in accordance with the protocols provided by the local health authorities. A temporary storage area should be assigned in the clinic for storage of medical waste 25 . Reusable instruments should be adequately pre-treated using oxidizing disinfectant, cleaned, sterilized, and stored in accordance with the local health authorities' protocol 25 . Double-layered packing, appropriate labelling, and gooseneck ligation has been suggested for medical waste generated from suspected/con rmed cases of Covid-19 25 . The contaminated disposable PPE including gloves, gowns, head covers should be safely disposed-off in a bag, within clinical area before entering non-clinical area. FFP level 2/3 mask should be worn by all staff members at all times.
Dental healthcare professionals are at high risk for acquiring and transmitting infection to their peers, families, and other patients due to possibility of exposure to suspected/con rmed covid-19 patients 36 . The risk is substantial due to aerosol generating procedures observed during routine dental care leading to subsequent development of fear, anxiety, mental/psychological challenges among dental professionals posed by 36 . This is especially important as emotional instability due to fear and anxiety can foster irrational behaviour and inadequate infection control practices 36 . We identi ed four articles examining awareness, perception, attitudes, and behaviour among dental professionals regarding Covid-19 pandemic 28, 33, 36, 37 . Khader et al conducted a cross-sectional study among 368 Jordanian dentists from different clinical settings to assess awareness, perception, and attitude regarding covid-19 and infection control practices 33 . Jordanian dentists were found to have limited knowledge about right incubation period, social distancing and mask for patients in the waiting area, hand hygiene practices, protective clothing for clinical and non-clinical staff, and over 80% reported to avoid treatment for suspected/con rmed covid-19 cases amid to fear of contracting disease 33 36 . This is further backed by scienti c evidence available from previous research showing unwillingness of dental providers to treat patients with infectious diseases such as SARS, HIV, tuberculosis, and MERS 36,37 . Use of rubber dam and pre procedural mouth rinse with oxidizing agent were ignored by majority of dental providers 36 . High level of anxiety was reported among dental professionals related to practice closure and subsequent economic implications 36 . A study evaluating psychological stress experienced by Israeli dentists and dental hygienists during Covid-19 pandemic identi ed that elevated psychological distress was signi cantly associated with having an existing chronic medical condition, low self-e cacy score, and contracting Covid-19 from patients 37 . The study further highlights that psychological distress among dental professionals may have long-term effects and recommends mental health education or workshops to enhance self-e cacy 37 . The role of local authorities in providing procedural guidelines in the face of pandemic is vital to help healthcare providers in making informed decisions. Adequate knowledge of incubation period is essential to determine safe period in treating suspected Covid-19 patients 33 . Use of rubber dam, protective clothing, and preprocedural mouth rinse play a signi cant role to prevent cross-contamination 33 .

Conclusion
The Covid-19 pandemic presents an existential crisis not just for the profession of dentistry but almost all other professions requiring human to human contact. With the rst phase of the pandemic now receding, it is possible that we could see health care authorities permitting elective treatments, but with all the infection control protocols and preventive measures as well as risk assessment of patients. Performing social distancing in the dental practice is almost impossible, hence only strict adherence to laid down protocols can protect the dental team and the patients from contracting . The future trajectory of Covid-19, the strength of individual health care systems, availability of rapid testing kits, possible vaccines and successful therapeutic options for  are factors that will in uence the dental practice and the additional precautionary measures that the dental practitioners adapt in the coming weeks and month. These measures will have to be scaled up and scaled down depending on the factors mentioned above.
The virus will stay for humanity for possibly years to come, hence the contingency plans and preventive measures will also stay with the dental profession for a long time to come 55 . The biggest concern will remain the aerosol generating nature of dental work. More research is required on aerosol's speci c risk assessment and measures that can protect the dental work force and patients from aerosol and droplet infection. The economic and psychological aspect of Covid-19 pandemic also need special attention as the pandemic is taking a tool of mental health of large segments of the population in these unprecedented and stressful times. It is important to ll in the gaps in knowledge regarding the complex nature of Covid-19's impact on dentistry, there are still blind spots regarding transmission and possible precautions which need to be removed with more research and a concentrated and uni ed effort by Governments, regulating authorities and health care researchers. The goal is to make the practice of dentistry secure in the era of The authors declare that they have no competing interests in this section Funding: