key: cord-0883918-8s3bcyo8
authors: Marshall, Steve; Duryea, Michael; Huang, Greg; Kadioglu, Onur; Mah, James; Palomo, Juan Martin; Rossouw, Emile; Stappert, Dina; Stewart, Kelton; Tufekci, Eser
title: COVID-19: What do we know?
date: 2020-09-21
journal: Am J Orthod Dentofacial Orthop
DOI: 10.1016/j.ajodo.2020.08.010
sha: 44e229a99c548d73218c89d1bed9b0a71a0ab6e7
doc_id: 883918
cord_uid: 8s3bcyo8

Evidence regarding provision of orthodontic care during COVID-19 pandemic is examined.

droplets (e.g. from sneezing, AGPs) tend to settle on surfaces, or unprotected mucosa of close contacts, and may be the source of direct or indirect virus transmission (also termed droplet transmission). 43 In experimentally simulated aerosolization of SARS-CoV-2, the virus maintains viability on surfaces for up to 72 hours indicating indirect (droplet) transmission can occur long after droplets establish contact with surfaces. [44] [45] [46] In contrast, small droplets (e.g. from coughing, talking, exhaling, or AGPs) produced by similar experimental aerosolization can evaporate into "droplet nuclei" and remain in the air for many hours. 44, 45, [47] [48] [49] The amount of viable SARS-CoV-2 in droplet nuclei remains unclear, but in subjects infected with other respiratory viruses, such as influenza, experiments comparing coughing and breathing suggest an equivalent production of viral RNA and replication-competent virus, detected at close range (< 12 inches). 50, 51 Although this has not been adequately studied for SARS-CoV-2, similar findings might be anticipated. [52] [53] [54] Moreover, saliva can be aerosolized during AGPs and is a known source of SARS-CoV-2 in infected individuals. 55 A timeline suggesting when infected individuals are most contagious has been informed by studies assessing viral shedding of COVID-19 patients by two methods: Detection of SARS-CoV-2 RNA and SARS-CoV-2 replication in cultured cells. 56 Viral RNA can be detected 1-3 days prior to the onset of COVID-19 symptoms, with the highest viral load in the upper respiratory tract occurring near the onset of symptoms followed by a decreasing viral load that is time-dependent based on disease severity. Viral RNA is shed for 1-2 weeks in asymptomatic cases and 3 or more weeks for mild to moderate cases of COVID-19. [57] [58] [59] [60] [61] [62] [63] [64] [65] [66] More severe symptoms require a longer time to reduce viral load. 57, 59, 60, [67] [68] [69] [70] [71] Reduction in viral load is accompanied by increases in neutralizing antibodies. 57 The findings from a limited number of studies evaluating virus viability during the course of COVID-19 illness suggest it is rare to find infected symptomatic individuals shedding viable virus after 9 days of symptom onset. 57, 61, [72] [73] [74] [75] A study of nursing home residents found viral RNA and viable virus in pre-symptomatic and asymptomatic subjects. 73 Taken together, these data suggest viral shedding, detected by viral RNA, may be an indicator of SARS-CoV-2 transmissibility prior to the onset of COVID-19 symptoms, but not later in the course of COVID-19 illness. However, measuring virus viability is more complex and may not be as sensitive as RNA detection. 57 includes AGPs and medical care without AGPs (non-aerosol generating procedures, non-AGPs) have not revealed a clear consensus on the risk of airborne transmission of SARS-CoV-2. 78 Airborne transmission of viable SARS-CoV-2 virus during medical AGPs on infected patients is suggested from previous studies of SARS-CoV-1, but has not been confirmed. 78 In situations where healthcare workers wearing personal protective equipment (PPE) attend to patients with COVID-19 and do not perform medical AGPs, direct airborne transmission of replicationcompetent SARS-CoV-2 has not been confirmed. 79 The results of hospital studies evaluating aerosolization of body fluids and respiratory droplets of SARS-CoV-1 infected patients generated during certain medical AGPs (tracheal intubation, non-invasive ventilation, bronchoscopy, etc.), suggest that airborne transmission of SARS-CoV-2 may be possible during these procedures. 79 However, the "possibility" is not clearly defined. High quality studies using consistent methodology to assess virus transmissibility during medical AGPs are lacking. 78 A 2012 systematic review of five case-control studies and five retrospective cohort studies on the transmissibility of SARS-CoV-1 during medical AGPs found a weak association with tracheal intubation across multiple studies and could draw no conclusions regarding other medical AGPs. 80 Subsequent studies on SARS-CoV-1 transmissibility during medical AGPs produced variable results. 43, 81 Similar controversial findings were found for Influenza A H1N1. 82 To date, although there is evidence suggesting that SARS-CoV-2 is likely transmitted via bioaerosol, 83 there is no direct evidence of airborne transmission of SARS-CoV-2 during medical AGPs when healthcare workers are wearing appropriate PPE, the risk of airborne transmission is not clearly defined. 78 Using precaution as the guiding principle in risk management, the CDC and WHO have adopted guidelines for barrier and environmental protection based on the hypothesis that airborne transmission can occur, even though a detailed understanding remains to be elucidated. From the CDC guidelines:

Development of a comprehensive list of AGPs for healthcare settings has not been possible, due to limitations in available data on which procedures may generate potentially infectious aerosols and the challenges in determining if reported transmissions during AGPs are due to aerosols or other exposures.

There is neither expert consensus, nor sufficient supporting data, to create a definitive and comprehensive list of AGPs for healthcare settings. 84 Scientific consensus on the transmission of SARS-CoV-2 during medical non-AGPs is not yet available. Results from studies designed to sample air for SARS-CoV-2 RNA, in hospital rooms where infected patients were cared for without medical AGPs, produced variable results. [85] [86] [87] [88] [89] [90] [91] [92] [93] [94] [95] [96] The studies finding the presence of viral RNA reported very low amounts. [85] [86] [87] [88] [89] [90] This experimental design assesses the presence of SARS-CoV-2 RNA but does not assess virus viability. Currently there are no studies reporting airborne viable (replication-competent) SARS-CoV-2 virus J o u r n a l P r e -p r o o f in hospital settings where infected patients are cared for, but not subjected to medical AGPs, by healthcare workers wearing surgical masks. 81 

In contrast to medical procedures in hospital and clinical settings, the risk of airborne SARS-CoV-2 infection during treatment of orthodontic patients has not been studied. Additionally, there are no reports of transmission of the virus in an orthodontic setting to elucidate clues regarding risk and transmission. Guidelines to mitigate the risk of SARS-CoV-2 airborne transmission during orthodontic treatment must be inferred from studies of SARS-CoV-2 infected patients during AGPs and non-AGPs in other healthcare settings. However, the extent to which AGPs and non-AGPs differ between the practice of medicine and the practice of orthodontics, and the impact of these differences on the risk of SARS-CoV-2 transmission has not been adequately addressed.

As potential SARS-CoV-2 transmission from pre-symptomatic and asymptomatic individuals remains a possibility, COVID-19 screening procedures will not prevent the unintentional treatment of some contagious individuals.

This poses an unknown risk of airborne transmission for both AGPs (mechanically-generated bioaerosol) and non-AGPs (patient sneezing, coughing, talking, exhaling) in orthodontic practice.

In orthodontic practice, AGPs include the use of rotary instruments (high-speed and slow-speed hand piece), airwater syringes (produce both splatter and aerosol), ultrasonic scalers, or air abrasion/polishing instrumentation on the tissues within the oral cavity. Use of these instruments generates aerosolized particles including particulates from dental materials and bioaerosol from aerosolized saliva and respiratory droplets. The particles/droplets generated range from 0.1-50 µm. The bioaerosol contents include live bacteria, fungus and viruses that increase the contamination of the air and surfaces in the area of patient treatment. [97] [98] [99] [100] Many reports have characterized the bacterial content of this bioaerosol, but there is a lack of research characterizing the production of viable airborne virus from AGPs used in orthodontic practice. 99, 101 Of particular importance is the size difference between viruses and bacteria. For example, Bennett et al. 102 found that bacteria (oral streptococci) in aerosols generated during dental AGPs dissipate within 30 minutes of their peak concentration.

However, streptococci are 10 -fold larger in diameter compared to SARS-CoV-2, which may limit their maintenance in aerosol compared to that seen for coronaviruses. 44, 45, [47] [48] [49] 103 How much aerosol is generated during orthodontic debonding?

Although the composition of particulates and bioaerosol generated during debonding of fixed orthodontic appliances has been widely studied (viruses excluded), the amount of bioaerosol generated during orthodontic debonding is not exactly known, and remains unknown for virus and virus particles. [98] [99] [104] [105] [106] [107] [108] [109] (For a J o u r n a l P r e -p r o o f comprehensive review, see Zemouri et al. 99 Eliades et al. 101 ). Evaluating various dental procedures in situ, Polednik 98 established that compared to background levels, airborne particulates increase approximately 6-fold for composite grinding, compared to a 2.5-fold increase for ultrasonic scaling. Composite grinding produced the most particulate aerosol of any dental AGP tested. Levels of bacterial aerosolization compared to background were ~1.5 -fold greater across dental AGPs tested.

Does aerosol generation differ when debonding is performed with a slow-speed vs. high-speed hand piece, or when debonding is performed with water vs. without water?

There are no studies addressing this question in situ, and no studies quantifying the amounts of bioaerosol generated during orthodontic debonding. The production of aerosol containing bonding adhesive and enamel particulates has been measured during removal of orthodontic adhesive from human teeth under laboratory conditions. 104, 105, 107, 109 One study suggests particle size differs between slow-speed and high-speed hand pieces, and the addition of water spray to the procedure results in a reduction of particle size generated during debonding. Slow-speed handpieces, with or without water spray, produced particles ~5-15 µm. High speed handpieces without and with water spray produced particles ~3 µm and ~0.5-1.3 µm respectively. 105 A second study by the same research group suggests debonding with a high-speed hand piece and water spray generates approximately 2-fold more adhesive and enamel particulates compared to debonding with a slow-speed hand piece without water spray. 107 Results from another research group evaluating smaller diameter particulates suggests the addition of water spray during slow-speed hand piece reduction of bulk composite reduces, by onehalf, the amount of airborne particulates smaller than 0.1 µm in diameter. 110 Taken together, these studies suggest that slower speed and water spray may reduce the amount of particulate aerosol produced. Additional studies are needed to confirm this.

It has been proposed that the use of water spray during orthodontic debonding improves debonding efficiency and thereby reduces the time that bioaerosol is produced. 101 Additional studies are needed to confirm this hypothesis.

At the present time, we cannot extrapolate from these laboratory studies to understand the amount of viable SARS-CoV-2 present in bioaerosol produced by various permutations of hand piece use during orthodontic debonding.

By and large, the clinical evidence for reduction of aerosols by the use of high volume extra-oral evacuation (HVE) comes from studies detecting the bacterial load produced during ultrasonic scaling. 111 Results from these studies have not been consistent. Significant bacterial load reductions (83-94%) 112, 113 or no reduction 114 Laboratory studies generating aerosol by various dental AGPs have suggested aerosol is reduced by the use of HVE. 107, 115, 116 However, the generalizability of findings from laboratory ultrasonic scaling studies to orthodontic debonding in situ is not fully understood.

Additionally, a recent meta-analysis of randomized and non-randomized trials assessing interventions to reduce bacterial aerosolization during dental AGPs suggests the use of HVE is not more effective than pre-procedural rinses with chlorhexidine or chlorine dioxide. 111 However, it is uncertain how this pertains to aerosolized viable virus.

At present, no studies have assessed the effectiveness of HVE during orthodontic debonding on the reduction of transmissible SARS-CoV-2. The use of HVE should be considered an prudent adjunctive measure to reduce the risk of virus transmission via bioaerosol during orthodontic debonding, but the efficacy of HVE use remains unclear. New evacuation instrumentation (e.g. high-flow extractor 117 ) are being developed and studied for their efficacy in reducing mechanically generated bioaerosol. Ongoing research will determine the benefit of their use during dental AGPs. 114 Currently, CDC recommendations for reducing the risk during AGPs in a dental setting include: 37

• Four-handed dentistry • Use of HVE • Dental Dams when practical • PPE including N95 mask, face shield, gown, gloves • Portable HEPA air filtration system properly situated Are air filtration/air purification systems effective in reducing aerosols generated during orthodontic debonding? Are HEPA filters required in air filtration/air purification systems for effective reduction of aerosols generated during orthodontic debonding?

To lessen the risk of airborne transmission of SARS-CoV-2 from the bioaerosol produced during dental AGPs, portable HEPA filtration systems (known as high-efficiency particulate air, high-efficiency particulate absorbing and high-efficiency particulate arrestance systems), are recommended by the CDC as a supplement to the barrier protection of PPE. 37 There is ample evidence that HEPA air purification reduces the concentration of airborne particles in the size range associated with airborne SARS-CoV-2, 118-121 but direct evidence for reduction of viable virus has not yet been reported. CDC guidelines suggest best practices for the positioning and use of portable HEPA systems in the operatory during dental AGPs, which is a subject of ongoing research. 37, 122 The use of PPE during orthodontic procedures J o u r n a l P r e -p r o o f As previously discussed, the infective potential of patient bioaerosol is not fully understood. Bioaerosol generated from coughing, sneezing, exhaling, or by mechanical aerosolization of saliva during patient procedures occurs as a range of drop and droplet sizes, all of which are potentially infective, by direct or indirect droplet contact with uncovered mucosal surfaces, or by inhalation of droplets or droplet nuclei. PPE is an important part of a system protecting doctors, staff and other patients by reducing the spread of viral respiratory infection. Other parts of that system are equally important: patient pre-screening, patient isolation from other patients, minimizing the number of staff caring for a patient, appropriate donning, doffing, and disposal of PPE, appropriate decontamination of surfaces and equipment, and appropriate biohazard waste management. 123 The WHO and CDC have recommended the use of PPE to match the potential mode of SARS-CoV-2 transmission during patient care. 37, 124 High-filtration masks (N95 or equivalent) are recommended as protection during aerosol generating procedures because of their barrier capability. However, in practice, uncertainty remains regarding the effect mask training, mask type and the re-use of masks and gowns on the true nature of protection . 123, 125, 126 Reports of headache among healthcare personnel during prolonged use of N95 respirators 127, 128 has prompted investigation of powered air-purifying respirators as a possible improvement in potential side effects of N95 respiratory use. 129

There is a lack of high-quality research comparing the effectiveness of the N95 respirator and the surgical mask in preventing transmission of SARS-CoV-2 to a healthcare worker under conditions of varying transmission risk.

A recent systematic review and meta-analysis of 4 randomized trials compared protection from respiratory illness for surgical masks vs. N95 respirators in healthcare workers potentially exposed to patients with acute viral respiratory illness (influenza). 130 Due to the heterogeneity of methods and outcome measures, the findings of no difference between surgical masks and N95 respirators are weakly supported with low or very-low levels of evidence. Comparing surgical masks and N95 respirators for protection from other respiratory viruses have produced similar findings. 126, 131 No trials have tested N95 respirator protection against SARS-CoV-2 transmission directly.

This evidence should be interpreted with caution. Laboratory studies indicate N95 respirators are far superior in blocking penetration of 10 -80 nanometer virions compared to surgical masks. 132 Trials conducted in healthcare settings suffer from variation in mask training, mask fitting, mask use, and mask removal that is absent in wellcontrolled laboratory studies. 125, 133 It is not yet clear that surgical masks offer equivalent protection to N95 respirators in situ.

What PPE is most appropriate during aerosol generating procedures vs. non-aerosol generating procedures?

The CDC recommends the use of face shields, gowns, and gloves during both AGPs and non-AGPs. 37 The CDC recommends the use of an N95 respirator, or a respirator offering equivalent or greater barrier protection to the inhalation of bioaerosol, during dental AGPs, and a surgical facemask during dental non-AGPs. 37 N95 respirators are recommended to limit inhalation of potentially infectious aerosol. Surgical facemasks offer a more limited "protection for the wearer against exposure to splashes and sprays of infectious material from others." 134 When should PPE be discarded and replaced during patient care?

The CDC recommends discarding gloves, gowns, surgical masks between each patient. 135 The CDC recommends N95 respirators be disposed after each use, but have provided guidance for extended use, or re-use after decontamination, during periods of reduced N95 availability. 135 Limited re-use is defined as using the same N95 respirator for multiple patients, but removing (doffing) after each patient encounter. The respirator is stored between encounters. Extended use is defined as using the same N95 respirator continuously during encounters with multiple patients. There are strict guidelines for extended use and limited re-use of N95 respirators. 135

The CDC has issued strategies for dealing with supply shortages of PPE that include decontaminating NIOSHapproved N95 filtering facepiece respirators (FFRs) without exhalation valves. Although knowledge gaps remain in the efficacy of FFR decontamination, moist heat, ultraviolet germicidal irradiation, and vaporous hydrogen peroxide, appear to be appropriate decontamination methods. However, FFR decontamination is meant to be implemented under strict guidelines. These guidelines should be thoroughly understood prior to implementing this strategy. 135

Two recent meta-analyses of randomized controlled trials, studying the effect of pre-procedural mouth rinses (PPMRs) on bacteria produced during dental AGPs, concluded there is moderate evidence that PPMRs (chlorhexidine, cetylpyridinium chloride, providone-iodine, or essential oils) significantly reduce aerosolized bacteria. 115, 136 There is no direct evidence for a similar effect of these oral antiseptics on aerosolized viruses. According to the CDC, "There is no published evidence regarding the clinical effectiveness of PPMRs to reduce SARS-CoV-2 viral loads or to prevent transmission. Although SARS-CoV-2 was not studied, PPMRs with an antimicrobial product (chlorhexidine gluconate, essential oils, povidone-iodine or cetylpyridinium chloride) may reduce the level of oral microorganisms in aerosols and spatter generated during dental procedures." 37 A number of narrative reviews suggest selected oral antiseptic rinses, including 1.0% hydrogen peroxide, have antiviral activity in vitro, but this indirect evidence requires well-designed trials to evaluate clinical efficacy in situ. [137] [138] [139] [140] [141] J o u r n a l P r e -p r o o f How much time should be allocated between patients when aerosol generating procedures are performed?

Currently, there is not enough information to answer this question directly. CDC guidelines for performing AGPs on patients known to be infected with SARS-CoV-2 require treatment in an airborne infection isolation room with a minimum of 6 air changes per hour and a minimum waiting time of 69 minutes to reduce potentially infectious aerosol by 99.9% 35, 142 Aerosol-generating treatment of asymptomatic or pre-symptomatic orthodontic patients poses a risk that is not quantifiable. The CDC has suggested evaluating HVAC systems for airflow patterns, rates of air exchange, and increased filtration, and the addition of portable HEPA filtration systems to reduce this risk. 37

There is no direct evidence for the efficacy of physical partitions reducing the risk of SARS-CoV-2 transmission in and open operatory facility. As part of Engineering Controls to reduce the risk of transmission associated with the potential treatment of asymptomatic or pre-symptomatic orthodontic patients, the CDC recommends floor to ceiling barriers between open operatory chairs to enhance the effectiveness of portable HEPA filtration units dedicated to each operatory chair. 37

Epilogue COVID-19 is a novel disease. Evidence for COVID-19 management and best practices is being generated rapidly.

While we have assembled the best available current evidence to this series of questions, it must be considered interim information and guidance. As the safe practice of orthodontics is our collective responsibility, the AAO task force on COVID-19 will continue to update our understanding of this disease and the impact of new information on the provision of orthodontic care.

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