Commentary

During pandemic events (HIV, COVID-19, etc.) and when there are no adequate therapeutic resources, the application of preventive guidelines is important to minimize the spread of infection [1]. Furthermore, this is important to reassure the population, pay more attention to vulnerable patients and stabilize the mood in the overly concerned population. In this social context it is also important to provide medical and dental  assistance through safe dental treatments. After the apparent pandemic reduction, individual anxieties and economic and social uncertainties remain high. Requests for dental care have significantly decreased (for prostheses, oral surgery, endodontics and restorations) mainly due to uncertain and insufficient insurance coverage and the high costs of dental therapies [2]. A recent survey of over 2,000 people from July 2020 shows that 40% of respondents said they did not feel safe in the dental practice during routine checkups or dental cleanings. Furthermore, 36% of respondents do not believe that dentists can control or stop the spread of COVID-19 [3]. The population has

changed the priorities of health needs, including for dental treatments. This is in line with the fact that dental patients require concrete operational safety for the prevention of any infection [2, 4-6].

Today, more than ever, all dental facilities must make infection prevention a priority and guidelines indicate the need to strictly adopt standard precautions, especially based on viral transmission. This procedural objective is fundamental for an adequate reopening of dental services. A recent Cochrane review reports on national recommendations for the re-structuring and reopening of dental services from 11 countries [7]. Unfortunately, this document and other international sources present highly variable details and procedures with a lack of univocal operational objectives that can demonstrate reasonable effectiveness. Obviously, in the event of a new pandemic situation, some recommendations will derive primarily from the characteristics and biological plausibility of the infectious agent (i.e. the SARS-CoV weakness to oxidants and pre-rinse mouthwashes) and from preventive and therapeutic experiences with other infectious diseases (SARS-Co-V, MERS, influenza). Therefore, the world dental community is rapidly gathering useful information to adequately structure the first methodological recommendations [8]. The "better prevention than cure" approach and the precautionary principle justify the adoption of rigorous and severe preventive measures for COVID-19 infection, even if scientific consensus may not yet have been reached and codified [9]. Up to now, guideline recommendations suffer of knowledge gaps regarding:

1. SARS-CoV-2 transmission by both small and large particle aerosol [10]
2. Lung and oral virus load and viral aerosol emissions in the early stages of disease or asymptomatic patients [11]
3. SARSCoV-2 stability and viability in aerosol [12] and different ventilation conditions in dental settings
4. Role of oral rinses in preventing the transmission of SARS-CoV-2 [13, 14]
5. Features of PPE, methods of donning and doffing, and training of practical relevance to dentistry [7, 15, 16]
6. Safety and operatory protocols for surgical dental care [17]
7. The overall economic evaluations in relation to infective adverse events [18-20] and patient safety [21].

Then, guidelines are expected to change quickly with additional results in relation to cost/benefit and their critical revision is needed if COVID-19 will become endemic [22]. Nevertheless, we would like to underline that:

1. The most frequent failing in infection prevention was poor hand hygiene and inappropriate glove use, which are standard precautions known to have high cost/benefit advantages [23, 24]
2. The consequence of an COVID-19 outbreak would be a shock for pockets in or out of the courts for any dental facilities analogously with other reported outbreaks [25-27]
3. It is difficult to prove an iatrogenic infection during COVID-19 pandemic; nevertheless, contact tracing (Italian Immuni App) and social media should put us on a grill [28, 29]

Recently, we and other authors discussed some problems which are going on during the application of guidelines [1, 22, 30-33] and their perspectives [22, 34, 35]. Others systematic review or meta-analysis began to rank the effectiveness of the existing interventions to reduce aerosolized microbes [36].  Here, we would like to contribute to the discussion on limited guidelines on elective and non elective dental surgeries [37, 38]. The role of SARS-CoV-2 blood transmission still remains uncertain and could likely be low [39]. Indeed, viral transmission by aerosols would be a burning and particularly current problem [10, 12]. The proposed reclassification of Bizzocca is based on the probability of contagion by one or more infectious agents via saliva, blood, droplets or aerosols for the dental team, for the patient under treatment or for the subsequent patients, without considering the surgical and intrinsic operative difficulties. Therefore, surgical procedures (e.g. oral soft tissue biopsy, mucogingival surgery, exodontic surgery), operationally characterized by low or absent aerosol and droplet production, were considered not particularly dangerous [38].

We would like to underline that the CDC defines all dental therapies that produce aerosols are at high infectious risk, such as the therapeutic treatments in anatomical regions where the viral load may be higher (tongue, oral and pharyngeal-mucous membranes) [40, 41]. Rigorous infection prevention is recommended during elective craniofacial surgery [42-45]. Up to now, dental implantology (DI) and regenerative bone surgery (RBS) are considered non elective dental surgeries. We think that DI and RBS should be re-proposed to patients with attention for knowledge gaps regarding to:

1. Devastating consequences in many tissues and organs of COVID-19 in older and the increased fatality rate after 50 yrs and patients with other medical co-morbidities [46]. It is well known that DI and RBS are requested mainly by patients elder than 50 yrs
2. Lasting disabilities COVID-19 survivors will face because of the combination of underlying chronic diseases, prolonged inflammation, and post-traumatic stress disorder [47]. Dental teams should be trained for medical emergencies [48]
3. The immune response to COVID-19 [49, 50, 51]. The SARS-CoV-2 infection may decrease T lymphocytes, as well as IFN-γ production by CD4+ T cells [52]
4. COVID-19 and smoking. Smoking increases SARS-CoV-2 receptors in the lung and this is rationally expected also in oral tissues [53]. Unfortunately, it is well known that smokers are particularly vulnerable to severe infections and dental implant loss
5. If asymptomatic (pooled estimate of 16%) and paucisymptomatic patients or infected people without symptoms (75-100% of these people subsequently developed symptoms) or infected people who never developed symptoms (23%) could have an altered response to inflammation and coagulation [39, 54]. Our belief in relation to our clinical experience and bibliographic data, dental triage would not currently be able to differentiate asymptomatic or pre-symptomatic patients from unaffected individuals [33]
6. Dental sedation precautions, recommendations and breath difficulties [55]
7. The ACE2 receptor that is a cellular doorway for the SARS-CoV-2 entry and infection of cells. Nevertheless, ACE2/Ang-(1-7)/MasR is an active player in alveolar bone remodelling [56, 57]. Briefly, angiotensin II increases the osteoclastogenesis, while inhibit the osteoblastic activity leading to a decrease in bone mineral density
8. The interactome between SARS-CoV-2 and host cell proteins, performed by Master Regulator Analysis. It showed a very complex interaction ranging from surface enzymes (ACE2) to RNA-processing proteins (DDX5) to mitochondrial constituents (BCL2), up regulation of MCL1, a positive regulator of apoptosis, a highly regulated and programmed cell death [58], that is important for bone regeneration

In conclusion, better guidelines on infection prevention, studies focussed on the effects of the COVID-19 epidemic on RBS and recommendations for selecting patients before DI are welcome to avoid post-surgery clinical and legal troubles. Basic research using human organ models on chips for virology and dedicated to dentistry will be a formidable challenge of the future [59].

Declaration of Competing Interest

Livia Barenghi had a service agreement with KerrKaVo and was a consultant for DentalTrey il Blog (http://blog.dentaltrey.it/), neither of which gave any input or financial support to the writing of this article. The authors (Alberto Barenghi, Francesco Spadari, Aldo Bruno Giannì) declare that there are no conflicts of interest regarding the publication of this paper.

Author Contribution

Livia Barenghi: Conceptualization, Methodology, Writing - original draft, Writing - review & editing. Alberto Barenghi: review. Aldo Bruno Giannì: review. Francesco Spadari: Methodology, Writing - original draft.

References

1. Jamal M, Shah M, Almarzooqi SH, et al. Overview of transnational recommendations for COVID-19 transmission control in dental care settings. Oral Diseases (2020): 1-10.
2. Fontana J, Murawski T. COVID-19: Impact to dental utilization. Milliman White Paper (2020).
3. Kulsrud Z. Dental patient survey shows 5 key shifts during COVID-19 (2020) https://www.dentistryiq.com/covid-19/article/14182336/dental-patient-survey-shows-5-key-shifts-during-covid19.
4. Maslow AH. A theory of human motivation. Psychological Review 50 (1943): 370-396.
5. Smith AJ, Wilson S, Read S, et al.  Patients’ perception of infection prevention in dental practice. American Journal of Infection Control 214 (2014): 337-339.
6. Shyagali TR, Bhayya DP. Patient’s attitude and knowledge towards the usage of barrier technique by orthodontists. International Journal of Infection Control 8 (2012): 1-8.
7. COVID-19 Dental Services Evidence Review (CoDER) Working Group. Recommendations for the re-opening of dental services: a rapid review of international sources (2020).
8. Meng L, Hua F, Bian Z. Coronavirus Disease 2019 (COVID-19): Emerging and Future Challenges for Dental and Oral Medicine. Journal of Dental Research 99 (2020): 481-487.
9. Meßerschmidt K. COVID-19 legislation in the light of the precautionary principle. The Theory and Practice of Legislation (2020).
10. Fennelly KP. Particle sizes of infectious aerosols: implications for infection control. Lancet Respir Med (2020).
11. Riediker M, Tsai D-H. Estimation of Viral Aerosol Emissions From Simulated Individuals With Asymptomatic to Moderate Coronavirus Disease 2019. JAMA Network Open 3 (2020): e2013807.
12. Stability and Viability of SARS-CoV-2. Letter to the Editor. N Engl J Med 382 (2020): 1962-1966.
13. Moosavi MS, Aminishakib P, Ansari M. Antiviral mouthwashes: possible benefit for COVID-19 with evidence-based approach. Journal of Oral Microbiology 12 (2020): 1794363.
14. Kelly K, Íomhair AN, McKenna G. Can oral rinses play a role in preventing transmission of Covid 19 infection?. Evidence-Based Dentistry 21 (2020): 42-43.
15. Gallagher JE, Johnson I, Verbeek JH, et al. Relevance and paucity of evidence: a dental perspective on personal protective equipment during the COVID-19 pandemic. British Dental Journal 229 (2020): 121-124.
16. Rollings L. FFP3 respirator face fit testing – what is it all about? British Dental Journal 229 (2020): 112-114.
17. Gugnani N, Gugnani S. Safety protocols for dental practices in the COVID-19 era. Evidence-Based Dentistry 21 (2020): 56-57.
18. Thusu S, Panesar S, Bedi R. Patient safety in dentistry – state of play as revealed by a national database of errors. Br Dent J 213 (2012): E3.
19. Ramoni R, Walji M. Creating a dental patient safety initiative Osap Symposium (2015).
20. Reuter NG, Westgate PM, Ingram M et al. Death related to dental treatment: a systematic review. Oral Med Oral Pathol Oral Radiol (2017): 194-204.
21. Yamalik N, Perea Perez B. Patient safety and dentistry: what do we need to know? Fundamentals of patient safety, the safety culture and implementation of patient safety measures in dental practice. International Dental Journal 62 (2012): 189-196. 
22. Ghai S. If COVID-19 becomes endemic will the current dental guidelines still remain valid? Oral Diseases  (2020): 1-2.
23. Barenghi L, Barenghi A, Diblasio A. Infection control in dentistry and drug resistant infectious agents: a burning issue. Part 2. InTech (2018).
24. Stankiewicz N. Dental infection control violations - an analysis of GDC Fitness to Practise cases between 2014-2018. British Dental Journal In Practice 33 (2020): 12-16.
25. Bradley KK. Dental Healthcare Associated Transmission of Hepatitis C. Final Report of Public Health Investigation and Response 2013 (2015).
26. Hatzenbuehler LA, Tobin-D’Angelo M, Drenze C, et al.  Pediatric Dental Clinic–Associated Outbreak of Mycobacterium abscessus Infection. Journal of the Pediatric Infectious Diseases Society 6.3 (2017): e116-e122.
27. Ross KM, Mehr JS, Greeley RD, et al. Outbreak of bacterial endocarditis associated with an oral surgery practice New Jersey public health surveillance, 2013 to 2014. JADA  149 (2018): 191-201.
28. Colorado Springs Pediatric Dentistry (2020).
29. Smile Orthodontics and Pediatric Dentistry (2020).
30. Barenghi L, Barenghi A, Gianni AB, et al. Problems on Going during the Application of Guidelines for COVID-19 Prevention in Dentistry. EC Dental Science 19 (2020): 79-88.
31. Chigurupati R, Panchal N, Henry AM, et al. Considerations for Oral and Maxillofacial Surgeons in COVID-19 Era: Can We Sustain the Solutions to Keep Our Patients and Healthcare Personnel Safe?. J Oral Maxillofac Surg 78 (2020): 1241-1256.
32. Kowalski K, Sanabria A, Ridge Ja, et al. COVID-19 pandemic: Effects and evidence-based recommendations for otolaryngology and head and neck surgery practice. Head & Neck  42 (2020): 1259-1267. 
33. Volgenant CMC, Persoon IF, de Ruijter RAG, et al. Infection control in dental health care during and after the SARS-CoV-2 outbreak. Oral Diseases (2020): 1-10.
34. Beltran-Aguilar E, Benzian H, Niederman R. Rational perspectives on risk and certainty for dentistry during the COVID-19 pandemic. American Journal of Infection Control (2020): 1-3.
35. Ren F , Rasubala L, Malmstrom H, et al.  Dental Care and Oral Health under the Clouds of COVID-19. JDR Clinical & Translational Research (2020): 1-9.
36. Koletsi D, Belibasakis GN, Eliades T. Interventions to Reduce Aerosolized Microbes in Dental Practice: A Systematic Review with Network Meta-analysis of Randomized Controlled Trials. Journal of Dental Research (2020): 1-11.
37. Interim Guidance for Management of Emergency and Urgent Dental Care (2020).
38. Bizzoca ME, Campisi G, Lo Muzio L. Covid-19 Pandemic: What Changes for Dentists and Oral Medicine Experts? A Narrative Review and Novel Approaches to Infection Containment. Int. J. Environ. Res. Public Health 17 (2020): 3793.
39. Transmission of SARS-CoV-2: implications for infection prevention precautions(2020).
40. Coronavirus Disease 2019 (COVID-19). Guidance for Dental Settings. Interim Infection Prevention and Control Guidance for Dental Settings During the COVID-19 (2020).
41. Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. International Journal of Oral Science 12 (2020).
42. Andrews BT, Garg MD, Przylecki W, et al. COVID-19 Pandemic and its Impact on Craniofacial Surgery. J Craniofac Surg (2020).
43. Sean P Edwards, Steve Kasten, Christine Nelson, et al. Maxillofacial Trauma Management During COVID-19: Multidisciplinary Recommendations. Facial Plastic Surgery & Aesthetic Medicine 22 (2020): 3.
44. Babak Givi, Bradley A Schiff, Steven B Chinn, et al. Safety Recommendations for Evaluation and Surgery of the Head and Neck During the COVID-19 Pandemic. JAMA Otolaryngology–Head & Neck Surgery 146 (2020): 579-584
45. Zimmerman M, Nikenke E. Approaches to the management of patients in oral and maxillofacial surgery during COVID-19 pandemic. J of Cranio-Maxillo-facial Surgery (2020).
46. Onder G, Rezza G, Brusaferro S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. JAMA (2020).
47. Servick K. For survivors of severe COVID-19, beating the virus is just the beginning. Science (2020).
48. Jevon P, Shamsi S. COVID-19 and medical emergencies in the dental practice. British Dental Journal 229 (2020): 19-24.
49. Li G, Fan Y, Lai Y, et al. Coronavirus infections and immune responses. J Med Virol 92 (2020): 424-432.
50. Kuri-Cervantes L, Betina Pampena M, Meng M, et al. Comprehensive mapping of immune perturbations associated with severe COVID-19. Sci. Immunol 5 (2020).
51. McKechnie JL, Blish CA. The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19?. Cell Host & Microbe (2020): 863-869.
52. Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clinical Investigation (2020).
53. Smith JC, Sausville EL, Girish V, et al. Cigarette smoke exposure and inflammatory signalling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract. Developmental Cell 53 (2020): 514-529.
54. Leao JC, Gusmao TPDL, Zarzar AM, et al. Coronaviridae-Old friends, new enemy! Oral Diseases (2020): 1-9.
55. Interim Guidance for Dentist Anesthesiologists Practicing in the Office-Based Setting During the COVID-19 Pandemic (2020).
56. Celso Martins Queiroz-Junior, Anna Clara Paiva Menezes Santos, Izabela Galvão, et al. The angiotensin converting enzyme 2/angiotensin-(1-7)/Mas Receptor axis as a key player in alveolar bone remodeling. Bone 128 (2019): 115041.
57. Jiaxue L, Lei C, Lifeng P, et al. Effect of Renin–Angiotensin System on Proliferation of Bone Marrow Mesenchymal Stem Cells and Its Interaction with AKT Signaling Pathway. Journal of Biomaterials and Tissue Engineering 9 (2019): 1398-1402.
58. Guzzi PH, Mercatelli D, Ceraolo C, et al.  Master Regulator Analysis of the SARS-CoV-2/Human Interactome. J. Clin. Med 9 (2020): 982.
59. Tang H, Abouleila Y, Si L, et al. Human Organs-on-Chips for Virology. Trends in Microbiology (2020).