key: cord-0737620-mxgbwebj
authors: Wilson, Jennie; Garson, Gail; Fitzgerald, Shaun; Llewelyn, Martin J.; Jenkins, David; Parker, Simon; Bois, Adam; Thomas, James; Sutcliffe, Katy; Sowden, Amanda; O’Mara-Eves, Alison; Stansfield, Claire; Harriss, Elinor; Reilly, Jacqui
title: What is the evidence that medical procedures which induce coughing or involve respiratory suctioning are associated with increased generation of aerosols and risk of SARS-CoV-2 infection? A rapid systematic review
date: 2021-07-08
journal: J Hosp Infect
DOI: 10.1016/j.jhin.2021.06.011
sha: 060352f46e5082d6bea4c6e0cf4b52943c56b16b
doc_id: 737620
cord_uid: mxgbwebj

The risk of transmission of SARS-CoV-2 from aerosols generated by medical procedures is a cause for concern. This rapid systematic review aimed to evaluate the evidence for aerosol production and transmission of respiratory infection associated with procedures that involve airway suctioning or induce coughing/sneezing. The review was informed by PRISMA guidelines. Searches were conducted in PubMed for studies published between 1/1/2003 and 6/10/2020. Included studies examined whether nasogastric tube insertion, lung-function tests, nasoendoscopy, dysphagia assessment or suctioning for airway clearance result in aerosol generation or transmission of SARS-CoV-2, SARS-CoV, MERS, or influenza. Risk of bias assessment assessed robustness of measurement, control for confounding and applicability to clinical practice. Eighteen primary studies and two systematic reviews were included. Three epidemiological studies found no association between nasogastric tube insertion and acquisition of respiratory infections. One simulation study found low/very low production of aerosols associated with pulmonary lung function tests. Seven simulation studies of endoscopic sinus surgery suggested significant increases in aerosols but findings were inconsistent, two clinical studies found airborne particles associated with the use of microdebriders/drills. Some simulation studies did not use robust measures to detect particles and are difficult to equate to clinical conditions. There was an absence of evidence to suggest that the procedures included in the review were associated with an increased risk of transmission of respiratory infection. In order to better target precautions to mitigate risk, more research is required to determine the characteristics of medical procedures and patients that increase the risk of transmission of SARS-CoV-2.

rather than actual routes of transmission, while clinical studies can provide evidence of actual transmission although are more difficult to conduct and interpret.

Some medical or patient care procedures are thought to increase the generation of respiratory aerosols. Following the SARS epidemic in 2003, the WHO defined 'high-risk AGP' as medical procedures that 'have been reported to be aerosol-generating and consistently associated with an increased risk of pathogen transmission' and recommended the application of enhanced precautions for staff performing them. 8 The SARS-CoV-2 pandemic has raised concerns about a range of other medical procedures that have the potential to generate respiratory aerosols either as a result of the procedure or because of its propensity to induce coughing or sneezing in the patient.

We undertook this review to evaluate whether medical procedures which induce coughing/sneezing or involve respiratory airway suctioning, generate infectious aerosols and are associated with a risk of transmission of respiratory infection, including SARS-CoV-2.

The procedures under consideration have not been previously defined as high-risk aerosol generating procedure (HR-AGP) but have been highlighted by clinicians as procedures of concern. 9 This review sought to evaluate evidence to determine if these procedures generate infectious aerosols and are associated with a risk of transmission of respiratory infection in order to inform guidance for healthcare professionals caring for patients with SARS-CoV-2. Two main questions were addressed:

Does evidence suggest that medical procedures which induce coughing/sneezing or involve respiratory airway suctioning result in infectious aerosol production?

And if yes, what is the associated risk of transmission of SARS-CoV-2?

As the assessment of evidence was required urgently to underpin guidance for use by healthcare professionals we adopted a rapid review approach, meaning that there was some deviation from standard systematic review procedures. 10 For example, although we produced a protocol, we were not able register it on Prospero as data extraction began before the protocol was finalised (Prospero requires registration before data extraction J o u r n a l P r e -p r o o f commences); the protocol has been published elsewhere for transparency. 11 This rapid systematic review was informed by PRISMA guidelines. However, it should be noted that specific rapid review guidelines are not currently available. 12 Therefore, to ensure transparency we provide a full account of the review procedures below.

Searches were conducted by an information specialist (CS) in PubMed for studies published between 1 st January 2003 and 6 th October 2020. The search terms are detailed in webappendix 1 and included terms reflecting aerosol generation and transmission from droplets and /or aerosols, respiratory secretions, coughing, sputum, and aerosols plus the set of procedures of interest (Table 1 ). In addition, the references of included articles were examined to identify any additional studies.

The population of interest was adults and children with or without clinically suspected or confirmed COVID-19 or other respiratory infection (SARS, MERS, and influenza) or a simulated exposure model (e.g. using human volunteers, cadavers etc). The exposure of interest was one or more of the 'procedures of concern' shown in Table 1 . The outcome of interest was the number and size of respiratory particles generated during the procedure and/or rate of infection with respiratory pathogens among exposed staff.

Study designs eligible for inclusion were case reports, case series, case control, outbreak studies, intervention studies (all designs) and systematic reviews reporting a search strategy Search results were screened using EPPI-Reviewer software. 13 One reviewer (JT) screened all titles and abstracts assisted by machine learning to prioritise potentially relevant papers.

A second reviewer then independently screened the titles and abstracts provisionally included by JT and the excluded titles and abstracts that machine learning identified as most likely to have been erroneously excluded. Disagreements were resolved by discussion. Two reviewers (GC, JW) then independently screened the full reports of included references (n=68) and there was no disagreement. Reference checking of papers flagged by the full-text screeners as potential sources of further evidence was undertaken by KS.

In line with best practice, available time and consistency requirements of a rapid review, one reviewer (KS) extracted all the data and a sample of 20% of papers were checked by a second reviewer (AO). 10, 14 An independent panel reviewed all the papers and evidence tables to check the accuracy of the data and interpretation of the evidence.

Since high quality evidence was unlikely to be available, evidence would be drawn from both experimental laboratory-based studies (such as cadaveric simulation studies) and

observational studies of clinical practice. Therefore, in line with recommendations for rapid reviews the quality assessment for each study was focused on factors most important for decision-making. 10 AO, KS, JT and AS developed a bespoke risk of bias tool to assess each study according to a) the robustness of measurement, b) control for confounding and c) applicability to clinical practice. These dimensions are illustrated in Figure 1 below. Details of the assessment for each study are provided in the Evidence Tables (Tables 2 -6 ) in the column 'Study contribution/limitations'.

J o u r n a l P r e -p r o o f 8 A standardised data extraction form was developed in order to produce a summary of each study. These summaries were then collated in evidence tables for each of the procedures of interest (nasogastric tube insertion, pulmonary lung function testing, suctioning for airway clearance, dysphagia assessment and nasoendoscopic procedures). Data were extracted on the following dimensions:

 Study details: Country, aim, design.

 Procedures and measures: procedures performed (on, by, where, number of repetitions) outcome measure type (e.g. virus transmission, aerosol size, spread, density) and method (e.g. virus transmission confirmed by antibody test, or aerosols captured by photodocumentation, particle sizer).

 Findings: Key conclusions and detailed findings e.g. relative risk of virus transmission with 95% confidence intervals, mean change in particle concentration etc.

 Risk of bias assessment: as described above.

The synthesis of study findings was organised according to each of the procedures of interest. Findings were narratively synthesised to examine if consistent patterns in the direction of effect could be identified. An overview of findings from systematic reviews involved examining the extent of relevant evidence and authors conclusions.

A total of 913 documents were identified in the search of which six were duplicates. A further three papers were identified from reference-checking and a further rapid systematic review published after the search was conducted. Following application of the inclusion criteria, 20 relevant papers were identified; 18 primary studies and two systematic reviews 

Nine of the 18 studies provided evidence on endoscopic sinus surgery [15] [16] [17] [18] [19] [20] [21] [22] [23] , six studies All studies aimed to determine whether procedures put healthcare workers (HCW) at risk, either by examining whether procedures generate aerosols or droplets [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [28] [29] [30] [31] [32] 29 Finally, several studies evaluated whether a range of devices are effective in reducing the spread of aerosols or droplets during procedures.

Devices included masks 23,24,25,29 , drapes 15 , smoke evacuation system 19 and suctioning. 19, 20, 21 Fewer than half of the primary studies were clinically-based involving actual patients 15, 18, [25] [26] [27] [28] 31 ; the remainder were simulations of procedures under experimental conditions and involved volunteers 30,32,22 ; cadavers 17, 19, 20, 21, 22, 23 ; human patient simulators 24,29 or porcine tissue 16 .

Of three studies measuring transmission, one employed a measure of the presence or viral genome (PCR test), one a test for antibodies, and one antibody tests or case definitions. Of the 15 studies measuring aerosols / droplets almost half used an optical particle counter or sizer to capture data 18, 19, 21, 22, 28, 31, 32 . The remainder used a method to enhance visualisation of aerosols or droplets so that they could be captured using video or camera technology, including fluorescein dye 15,17,20 ,23,29 , smoke 17, 24 or green laser 30 . One study used both smoke and fluorescein dye 17 .

Both studies employed a retrospective cohort design and examined the association between performing nasogastric tube insertion and SARS infection among HCW in Canada (Table 2) .

One study 26 A study by Greening et al used a simulation design involving healthy volunteers to examine aerosol / droplet production following pulmonary lung-function tests (tidal breathing, forced expiratory volume, slow vital capacity (SVC) following inspiration from functional residual capacity, and SVC following inspiration from residual capacity) and association with coughing (see Table 3 ). 32 The study found very low particle emission in tidal volume and SVC from functional residual capacity, and low emission during forced expiratory volume.

Coughing resulted in the highest mass of exhaled particles compared with all other manoeuvres, with a 640% (95%CI 230-1570, P < .01) increase compared with SVC following inspiration from functional residual capacity. 32

Whilst the study provides evidence about aerosol / droplet generation from pulmonary lung-function tests there are several limitations. Firstly, the study used 'healthy volunteers'

and it is unclear how aerosol production might be affected in those with lung conditions or with a viral infection. Secondly, in-line filters, which would be routinely used in lung function laboratories, were not used during these tests and these would effectively filter airborne particles. Thirdly, it is unclear how appropriate the Particles in Exhaled Air particle sizer / counter system used in this study was for measuring aerosols / droplets in patients with a virus; the authors note that it registers mostly small droplets from the small airways, and virus are likely to be present in droplets from both upper and lower respiratory tract.

Two studies were observations of clinical practice, examining aerosol / droplet generation among patients whose SARS-Cov-2 infection status is unknown 15 or patients who have received a negative test result. 18 Of the remaining seven studies, most were cadaveric simulations 17, 19, 20, 21, 22, 23 , and one used porcine tissue 16 (see Table 4 ). The findings from these studies were not consistent.

Of the two clinical observations, one 18 Table 4 ).

One study conducted in the USA used a clinical observation design and examined aerosol / droplet generation among patients who have received a negative SARS-Cov-2 test result.

The remaining three studies were simulations (one cadaveric and two healthy volunteers).

The findings from these studies were not consistent. One clinical observation 31 found that J o u r n a l P r e -p r o o f diagnostic nasal endoscopy with a rigid endoscope was not associated with increased particle aerosolization, but that sinonasal debridement, endonasal non-powered and suction instrumentation were associated with increased particle aerosolization compared with pre-procedure levels (mean increase 0.0869 particles/cm 3 , 95%CI 0.029-0.144, p=0.005; 0.105 particles/cm 3 , 95%CI 0.050-0.1599, p=0.001). The three simulation studies 22,23,30 all found evidence of droplet or aerosol formation during nasendoscopy and associated patient behaviours such as sneezing (see Table 5 ).

None of the studies provide evidence in patients with COVID-19 or other respiratory infections and each of the studies had some limitations. The measuring device (an optical particle sizer) used in the clinical observation was not able to detect the smallest particles and this study provided limited information about the experimental setup and sampling location with respect to ventilation. The cadaveric and healthy volunteer simulation studies did not account for patient factors such as nasal secretions, fever etc. and not all used robust measures or accounted for potential confounders (see Table 5 ).

Three studies used a retrospective cohort design, of which one evaluated SARS-Cov-2 bathing, intravenous access, physical examination and no contamination was found on face or face shield during suctioning. 29 Finally, a clinical observation study on H1N1 pandemic patients found an increase in aerosol generation during respiratory/airway suctioning but this was not statistically significant (OR = 4.11 (0.50-34.0). 28 The particle size generated during suctioning were smaller than those collected during baseline but the difference was not significant. 

Two systematic reviews were identified that included primary research and addressed the review questions ( 

We identified and evaluated evidence for the generation of respiratory aerosols during nasogastric tube insertion, cardiopulmonary exercise and lung function tests, nasoendoscopy, swallowing assessment and oral suction and their association with risk of transmission of SARS-CoV-2 and similar respiratory infections.

The evidence is predominantly derived from experimental simulation studies which used optical particle counters or digital photography to measure respiratory particle dissemination or attempted to simulate droplets with fluorescein or aerosols with smoke. Although simulation studies provide some evidence of the potential for airborne respiratory particles to be generated from these procedures, the presence of aerosols does not prove an increased risk of transmission of respiratory viruses. In order to demonstrate a clinically significant risk of airborne infection, aerosols must contain enough infectious virus to enable an infective dose to reach the specific host cell tissue that the virus is able to infect. 36 The evidence needs to demonstrate a significant increase in aerosols compared with background levels and that the aerosols are able to carry virus and transmit infection.

Only one study on oral suctioning 28 set out to detect influenzas virus in respiratory particles but did not attempt culture to establish if the particles could transmit infection.

Epidemiological evidence from studies that explored the risk of developing respiratory infection in personnel who performed the procedure is limited and only found for nasogastric tube insertion and suctioning. These studies did not demonstrate an association between performing these procedures and the risk of SARS, although the risk may be different in relation to SARS-CoV-2.

The potential for respiratory infections to transmit by an airborne route is dependent on a complex set of parameters which influence the generation and behaviour of respiratory particles. Conventionally, airborne particles have been distinguished as droplets which settle rapidly because of their mass, and aerosols which evaporate to form droplet nuclei and travel longer distances. 37,3 Droplets were perceived to be the primary risk of transmission when a susceptible person is in close proximity. 4, 8 However, it is now recognised that the dynamics are more complex and affected by a number of factors including force and volume of exhalation as well as humidity, temperature and airflow in the surrounding environment which affect the rate of evaporation and dissemination of particles. 6 Natural respiratory activities such as breathing and talking can generate a broad range of particle sizes, from submicron aerosols to large droplets. Using an expiratory droplet assessment kit (0.5 μm -20 μm) on healthy volunteers, J o u r n a l P r e -p r o o f Gregson et al (2020) 5 found an association between amplitude of speaking or singing and increased concentration of short-range aerosols but also a significant variation in particle emission between individuals. Indeed, results from different studies on the fluid dynamics of respiratory particles vary by orders of magnitude reflecting both the complexity of the phenomenon and approaches to measurement. 6 One of the concerns related to the procedures included in this review was their tendency to induce coughing. The mechanism by which coughing generates respiratory particles involves high-speed airflow over the mucus lining the airway and this generates a higher concentration of respiratory particles compared with speaking. 7 The initial particle cloud has a high concentration of droplets which settle rapidly. The smaller particles remain in suspension and travel further. The evaporation of smaller droplets into droplet nuclei depends on the ambient temperature and relative humidity. 38 However, given the greater mass of droplets expelled by either coughing or speaking these particles contain a high proportion of the fluid, and therefore virus, expelled. The amount of virus expelled will also depend on the viral load which will vary depending on the severity of the infection and specific regions of the respiratory tract that are affected. 7 The competing risks of more virus in larger droplets at lower concentration versus a higher concentration of smaller droplets with lower viral load have not been well studied for coughing. However, the risk of being exposed to an aerosol containing virus appears to be lower than the risk due to larger droplets at close range. The added risk of being exposed to a virus-containing aerosol particles from an aerosol generating medical procedure appears to be low relative compared with the general risk of exposure to expiration from a patient.

In a light-scattering study the authors estimated that during 1 min of loud speaking at least 1,000 virion-containing droplet nuclei would be generated and remain airborne for more than 8 min. Nevertheless, at a saliva viral load of 7×10 6 copies per millilitre the probability that a 3μm droplet nucleus contains a virion is only 0.01%. 39 Viral emissions associated with coughing are likely to be considerably higher than for breathing 40 with more virus being contained in larger droplets, which present a greater risk during close contact rather than via longer range aerosols. Therefore, the risk of aerosol infection from patients in the There are few other systematic evidence reviews that address these medical procedures.

One was conducted prior to the COVID-19 pandemic. It informed the concepts of high risk AGPs and drew similar conclusions to our review in relation to nasogastric tube insertion and suctioning. 33 There is only one robust review related to SARS-CoV-2, this is focused on nas(o)endoscopy and, although did not identify all the evidence included in this review, drew similar conclusions. 34

Overall, we identified an absence of evidence to suggest that these procedures are The paradigm for AGPs needs further consideration to better combine evidence from aerosol and infection prevention and control science. More research is required to determine the characteristics of both medical procedures and patients that increase the risk of transmission in order to better target precautions to mitigate the risk.

This review was limited in scope and because undertaken within a short timeframe was restricted to publications in PubMed. However, this would be expected to capture the main publications on this topic and references from the included studies and other systematic reviews were assessed to help mitigate this. Findings related to other respiratory viruses may not be comparable with SARS-CoV-2 because of difference in transmission dynamics. J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f Other concerns? Limited evidence re nasogastric tube.

J o u r n a l P r e -p r o o f Most lung function laboratories will use in-line filters which would effectively filter airborne particles during these tests.

Are measurement tools appropriate / robust? Unclear: Authors note that 'the PExA system registers mostly small droplets from the small airways, and virus are likely to be present in both upper and lower respiratory droplets.' The measurement of particle mass means no data about particle size.

Does the study design control for potential confounders? Yes: Manoeuvres were performed using particle free HEPA filtered inspiratory air, but no particle filter between exhalation and sampling.

The authors note that manoeuvres also included a breath hold before exhalation which may result in lower flow rate and particle release. 

Key findings: "In contrast to sole mechanical stress with passive instruments, all active instruments (laser, drilling and electrocoagulation) released particles and aerosols."

Non-powered instrument without suction: No particle or aerosol formation detected.

Non-powered instrument with suction: No particle or aerosol formation detected.

Laser treatment: Droplets -A highly directed ejection of very fine droplets was observed under microscope. Aerosols -Laser-induced aerosol formation "considerable and surpassed all other surgical intervention techniques".

Drilling: Droplets -"clearly detectable particles". Aerosols -"effect represented a spray mist rather than a gaseous aerosol." Cautery: Droplets -"strongest effect in comparison to all other intervention techniques". Aerosols -"considerable aerosol formation".

Is the study a reasonable representation of real-world clinical practice? No: Experimental simulation, influence of breathing and nasal secretions not accounted for. Test chamber does not correspond to the spatial dimensions of an oral or nasal cavity. Experiments undertaken for 3 minutes only -unclear if consistent with real-world procedure duration.

Are measurement tools appropriate / robust? Unclear: Good reliability -"To eliminate inter-and intraobserver variability, measurements were performed fully automatic with different computer based algorithms". But unclear how sensitive video footage will be to capture aerosols, particularly smallest size.

Does the study design control for potential confounders? Yes: External activation of powered instruments: "We activated the drill external to the cadaver but within the mask instrument aperture, both with and without negative pressure. Significant contamination was observed within the mask, but none was evident externally."

if checked with ultraviolet for residual droplets.

Other concerns? Small study. Key findings: Drilling and microdebrider use, but not non-powered instrumentation, were associated with a significant increase in airborne particle concentrations. The increased concentrations were localized to the area of the operating surgeon.

Non-powered instrumentation: Significant increases in airborne particle concentration were not seen for non-powered instrumentation with suction (mean change = 716 p/ft3; p=0.340).

Microdebrider: Significant increases in airborne particle concentration were measured at the surgeon position with the microdebrider (mean change =1825 p/ft3; p=0.001)

Drilling: Significant increases in airborne particle concentration were measured at the surgeon Is the study a reasonable representation of real-world clinical practice? Yes: live patient procedures in standard operating room.

Are measurement tools appropriate / Robust? Unclear: Particle sizer calibrated to national standards; repeated measures, 133 measurements made during 5 surgeries. 73% of particles were near the lower limit of detection (3 um) where counting efficiency of instrument is 50% and the size distributions indicate that a significant fraction is less than 0.3 μm.

Does the design control for potential confounders? Yes: Particle concentrations compared to preinstrumentation levels.

Other concerns? "The localized particle effect described in this study quantifies aerosol concentrations at distinct positions, and therefore is limited in describing exposure risk to staff who move about freely in the operating room, such as the nurse." as compared with FESS with the ring suction (P = .07).

Microdebrider: There was no significant difference in total particle concentration during FESS performed with powered suction microdebrider as compared with baseline (mean difference, -0.025 particles/cm3; P = .83). Both suction interventions resulted in decreased aerosol concentrations at larger particle sizes but increased concentrations at smaller particle sizes as compared with the suctioning microdebrider alone

Drilling: High-speed endonasal powered drilling of the sphenoid rostrum generated a significant increase in total aerosol concentration as compared with baseline (mean difference, 11.44 particles/cm3; P<.001) with significant increases of particles ranging from 0.30 to 2.69 µm. All 3 suction intervention conditions had significantly decreased aerosol concentrations as compared with no suction (P<.001).

Cautery: Needle tip electrocautery of the nasal mucosa along the septum and inferior turbinate without suction demonstrated a significant increase in total aerosol concentration as compared with baseline (mean difference, 1.58 particles/cm3; P<.001). Rigid suction plus the surgical smoke evacuation system resulted in the greatest decrease in aerosol generation, with concentrations significantly lower than rigid suction alone in 10 particle size ranges (P = .015). measured every second for 1 minute. HEPA filtration system used between experiments to return aerosol level to baseline and allow for detection of low particle concentrations. Particle sizer positioned to accurately represent the aerosol risk to the operating surgeon and surgical technologist.

Ultrasonic aspirator: The use of an ultrasonic aspirator on frontal bone resulted in significant increases in total aerosol concentration (mean difference, 4.41 particles/cm3; P < .001).

Conditions from both the rigid suction plus suction ring and the rigid suction plus surgical smoke evacuation system had significantly decreased aerosol concentrations as compared with the rigid suction alone. Surgical evacuation smoke system was used with rigid suction for drilling / cautery but not for the nonpowered instrument FESS and microdebrider. 

-Nasal endoscope -Non-powered instrument -microdebrider -drilling (with and without suction) -external activation of powered instruments -ultrasonic aspirator

-suction used with drilling On: Cadaver head specimen (n=2) Key findings: "Our results indicate that there is very little droplet generation from routine rhinologic procedures. The droplet generation from drilling was mitigated with the use of concurrent suction. Extreme caution should be used to avoid activating powered instrumentation outside of the nasal cavity, which was found to cause droplet contamination."

Nasal endoscope: No observable fluorescein droplets were noted in the measured surgical field in any direction. Microdebrider: No observable fluorescein droplets were noted in the measured surgical field in any direction for septoplasty with microdebrider-assisted turbinoplasty. Limited droplet spread was noted under microdebrider FESS (2 droplets within 10 cm of cadaver head, all less than 1 mm in size).

No observable fluorescein droplets were noted in the measured surgical field in any direction for drilling of the sphenoid rostrum with a cutting burr, drilling of the frontal beak with a diamond burr, drilling of the sphenoid rostrum with a diamond burr with concurrent suction and drilling of the frontal beak with concurrent suction. Limited droplet spread was noted under drilling of the sphenoid rostrum with a diamond burr (8 droplets within 12 cm of cadaver head, all less than \1 mm in size) and drilling of the frontal beak with a cutting burr (5 droplets within 9 cm of cadaver head,\1 mm in size). The use of a concurrent suction while drilling resulted in no contamination.

Limited droplet spread was noted under control condition of the drill placed outside the nose (0.5 cm droplet on chest, 11 spots within 13 cm, largest 2 cm in size).

Measurement of droplets only -no evidence on very small or airborne particles.

Does the study design control for potential confounders? No: Authors do not report assessments preexperiment to ensure any baseline droplets not associated with the procedure are accounted for.

Other concerns? Most procedures only performed once.

Ultrasonic aspirator: No observable fluorescein droplets were noted in the measured surgical field in any direction for ultrasonic aspirator on the left sphenoid sinus, use of the ultrasonic aspirator on the right frontal sinus, and external activation of the ultrasonic aspirator. Key findings: "The use of nasopharyngeal suctioning via the contralateral nostril minimizes airborne particulate spread during simulated sinonasal drilling and cautery."

Drilling without suction: Significant particulate generation in the 1-μm to 10-μm range during drilling of sphenoid rostrum (p <0.001, U = 56, difference between medians = 120.5 particles/L) and anterior nasal septum/anterior medial maxillary wall (p < 0.001, U = 26, difference between medians = 403.6 particles/L, Mann-Whitney U test)

Drilling with suction: With the suction turned on throughout the drilling period, significant 1-μm to 10-μm airborne particulate generation over baseline concentrations was not observed in either posterior or anterior drilling conditions.

Electrocautery without suction: Significant airborne particulate generation in the 1-μm to 10-μm range was observed in the 60-second period following electrocautery (p < 0.001, U = 0, difference between medians = 120.5 particles/L), compared to matched-condition background levels.

Is the study a reasonable representation of real-world clinical practice? No: Cadaveric simulation, influence of breathing and nasal secretions not accounted for.

Are measurement tools appropriate / robust? Unclear: Particle sizer. The methods are appropriate for 1 μm to 10 μm diameter size range. However, droplets (larger particles) are not measured as the authors point out. Especially close to the source larger particles could dry further and reduce in size. Figure 4 suggest particle numbers are nonzero at the upper size range. When scaled by volume of particles, the majority of the volume may be at higher sizes. Key finding: "Transnasal drill and cautery use is associated with significant airborne particulate matter production in the range of 1 to 10 µm under surgical conditions."

Nasal suctioning: Did not produce significant detectable airborne aerosols in the range of 1 to 10 µm.

Non-powered instrument: Did not produce significant detectable airborne aerosols in the range of 1 to 10 µm.

Microdebrider: Did not produce 1-to 10-µm airborne aerosols over 10 sampling periods (5 minutes).

Drilling: 3 separate drilling conditions were performed: Suction drill at 12,000 rpm; Diamond drill at 70,000 rpm; and Cutting drill at 70,000 rpm.

Is the study a reasonable representation of real-world clinical practice? No: Cadaveric simulation of surgery; no accounting for patient breathing / secretions. Volunteer-based clinical simulations do not account for patient characteristics -e.g. fever, increased secretions etc.

Are measurement tools appropriate / robust? Unclear: Optical particle sizer able to measure particles from 1 to 10 µm. However, droplets (larger particles) are not measured as the authors point out. In addition, the lower detection limit of 1um may have precluded measurement of a large number of aerosols given that highest particles

nasendoscopy -see table 5 for details.

Measure: Aerosols

Method: Optical particle counter / sizer (OPS 3330; TSI Inc).

In all 3 conditions, significant airborne aerosol generation in the range of 1 to 10 µm was observed. (P < .001 Mann-Whitney U test).

Electrocautery: Transnasal electrocautery of the inferior turbinate demonstrated significant particle generation in the range of 1 to 10 µm over background in four 30-second samples (P < .001; Mann-Whitney U test).

counts by size (see figure 1c ) are at the lowest end of the scale. Does the study design control for potential confounders? Yes: Baseline aerosols measured, between experiments allow for verification of return to baseline concentrations. Suction utilized to evacuate any retained intranasal particulates following drilling and electrocautery. The clinical examination room (111 sq ft) and the surgical laboratory (726 sq ft) were equipped with air exchangers operating at a rate of 6 total air changes per hour.

Other concerns? The choice of units for the results (particle counts by size over a period of timed data rather than concentration) prevents comparison with other studies and a quantitative assessment of how much aerosol was generated or what the representative concentrations were. Where: Laboratory.

Procedure repetitions: Not reported.

Outcomes measured:

Method: Fluorescein solution (0.2 mg per 10 mL) and quantified using a blue-light filter and digital image processing. Images assessed using ImageJ software Nasal endoscopy: No fluorescein-stained droplets were observed with a 0-degree endoscope.

Suctioning: No fluorescein-stained droplets were observed from nasal suctioning with 8-French Frazier suction.

Non-powered instrument: No fluorescein-stained droplets were observed from through-biting of the middle turbinate.

Microdebrider: No fluorescein-stained droplets were observed from suction microdebrider applied to the posterior septum.

External activation of microdebrider: No fluorescein-stained droplets were observed from external activation after tissue soilage.

Drilling: High-speed drill at 70,000 rpm with a 5mm cutting to remove bone at the sphenoid rostrum and nasal beak resulted in droplets observed in multiple distribution regions between 6 and 30 cm away from the nare. Maximum fluorescence intensity was significantly different in affected areas in the drilling conditions compared with baseline (p <0.01, two-tailed t test).

External activation of drill: External drilling had significantly more distribution regions affected than non-drill surgical conditions (p < 0.05, Fisher's exact test).

Simulated sneeze with mask devices: Our data confirm that a simulated sneezing event can generate aerosols that settle maximally between 30 cm from the nare but can extend up to 66 cm.

that smaller particles of concern for airborne transmission were not formally assessed. There are few details on the atomisation and the provided reference does not provide relevant details.

Are measurement tools appropriate / robust? Unclear: Unblinded review of presence or absence of fluorescent aerosolized droplet contamination verified by 2 separate authors. Authors note that it is possible that the microdebrider was capable of producing aerosols below estimated size detection limit of 20 μm.

Does the study design control for potential confounders? Yes: Background fluorescence from a matched control condition was subtracted.

Other concerns? Limited detail on methodology and appears that each procedure may have been performed only once.

Spread of these aerosols was effectively prevented by both the intact and VENT mask conditions. Outcomes measured:

Measure:

-Aerosol concentration

Key findings: "Diagnostic nasal endoscopy with a rigid endoscope is not associated with increased particle aerosolization in patient for whom sinonasal debridement is not needed. In patients needing sinonasal debridement, endonasal cold [non-powered] and suction instrumentation were associated with increased particle aerosolization."

Rigid endoscope [during diagnostic endoscopy]: Mean particle concentration 6,021 p/ft3. Nonsignificant mean difference of −173 p/ft3 (95% CI −1,139 to 793; P = .698) compared to preprocedure concentrations. Aerosols labelled in one figure appear to come directly from the nasal spray rather than the patient.

Unclear whether nasendoscopy was rigid or flexible. 

Nasal endoscopy: Nasal endoscopy generated significant airborne aerosols (P < .05, U = 10, n = 8; Mann-Whitney U test).

Topical spray: Airborne aerosols comparable to those generated with sneezing (P<.01, U = 0, n = 4; Mann-Whitney U test).

Patient behaviours: Panting and coughing generated detectable 1-to 10-µm aerosols that were not significantly greater than background. Speech generated significant airborne aerosols (P < .01, U = 6.5, n = 10; Mann-Whitney U test). Simulated sneezing generated the most airborne particles per minute by an order of magnitude (P < .01, U = 0, n =4; Mann-Whitney U test).

Surgical mask alone attenuated airborne aerosol generation; however, statistically significant aerosol escape was still detected (P<.05, U = 2, n = Where: Laboratory.

Key findings: "Among outpatient conditions, a simulated sneeze event generated maximal aerosol distribution at 30 cm, extending to 66 cm. Both an intact surgical mask and a modified VENT mask eliminated all detectable aerosol spread."

Nasal endoscopy: No fluorescein-stained droplets were observed with a 0-degree endoscope.

Simulated sneeze: Our data confirm that a simulated sneezing event can generate aerosols that settle maximally between 30 cm from the nare but can extend up to 66 cm.

Simulated sneeze with mask devices: Spread of these aerosols was effectively prevented by both the intact and VENT mask conditions.

Is the study a reasonable representation of real-world clinical practice? No: There are few details on the atomisation (simulated sneeze) such that it is difficult to determine the representativeness of the findings. However, the authors note that because the atomizer produces sprays between 30 and 100 μm smaller particles of concern for airborne transmission were not formally assessed. Outcomes measured:

Method: Fluorescein solution (0.2 mg per 10 mL) and quantified using a blue-light filter and digital image processing. Images assessed using ImageJ software measured droplet size appears to be the size of the droplet when deposited on the surface and there doesn't appear to be a correction for size when airborne.

Does the study design control for potential confounders? Yes: Background fluorescence from a matched control condition was subtracted.

Other concerns? Limited detail on methodology and appears that each procedure may have been performed only once. Where: Not reported.

Procedure repetitions: Not reported.

Outcomes measured:

Measure: Transmission.

Method: Nasopharyngeal and oropharyngeal specimen testing.

Key finding: Airway suctioning was performed by seven HCW exposed to an infected patient; none developed SARS-Cov-2 infection.

Suctioning: Airway suctioning was not performed by any of the 3 HCW with SARS-CoV-2 infection, and was performed by 7 (21%) of the 34 HCW who were exposed but not infected. Where: Hospital ward / room Key findings: Respiratory/airway suctioning "appears to be related to an increased likelihood of viral aerosol generation." Results indicate that respiratory and airway suction "tends to produce aerosols of smaller particle sizes than baseline levels" but the difference was not statistically significant Details:

Particle size: Compared to baseline samples the RNA recovered during respiratory and airway suctioning were smaller. In baseline the majority of RNA (78.7%) were found in particles larger than 7.3 µm. In suctioning Is the study a reasonable representation of real-world clinical practice? Yes: clinicbased evaluation.

Are measurement tools appropriate / robust? Unclear: Authors report that May impinger does not collect particles <,0.86 µm aerodynamic particle size, several studies have reported finding influenza RNA in air particles <,1 µm, thus it is possible that some of the aerosolized RNA was missed.

Does the study design control for potential confounders? Yes: Baseline samples taken when no activity that could be defined as an AGP was taking place. Staff respirators / the majority of RNA (77.6%) were found in particles smaller than 7.3 µm.

Aerosol generation: An increased probability associated with airway suctioning but not statistically significant (OR = 4.11 (0.50-34.0)).

vaccinations mean that it is "unlikely that the influenza aerosols could have been generated by anyone other than the patient on whom the AGP was being performed. Measurements taken at stationary point 1m from procedure and within the personal breathing space Does the study design control for potential confounders? Yes: Blank samples (negative controls) of aerosol sampling devices were used to correct measured values and sample extraction efficiency. For droplets measures are obtained (i) prior to the start of the healthcare activity (as a baseline), (ii) directly after the healthcare activity and (iii) after doffing PPE.

Other concerns? It is difficult to justify comparing the different tasks quantitatively (amount of fluorescein in samples) because of the starting conditions. For example, for intubation 300ml of liquid has been 'poured through mouth to lungs and stomach' compared to 100 ml poured onto two areas of the body for bathing. In the latter case all of the fluorescein will be external, while in the former it may be only a small amount that comes into contact with the endoscope.

*Evidence on suction for reduction of aerosol dispersal can be found in table 3 on nasendoscopy and nasal electrocautery J o u r n a l P r e -p r o o f 

World Health Organization (2020b) Mask use in the context of COVID-19 -Interim guidance

COVID-19: Guidance for maintaining services within health and care settings

Physico-chemical characteristics of evaporating respiratory fluid droplets

Particle sizes of infectious aerosols: implications for infection control. Viewpoint. The Lancet Resp Med

Comparing the Respirable Aerosol Concentrations and Particle Size Distributions Generated by Singing, Speaking and Breathing

Biological fluid dynamics of airborne COVID-19 infection

Modality of human expired aerosol size distributions

Infection prevention and control of epidemic-and pandemic prone acute respiratory infections in health care

Position statement on AGPs/PPE

Cochrane Rapid Reviews Methods Group offers evidence-informed guidance to conduct rapid reviews

A rapid systematic review of medical procedures, which induce coughing to establish if they can produce an increased risk of an infectious aerosol of SARS-CoV-2. Protocol

EPPI-Reviewer: advanced software for systematic reviews, maps and evidence synthesis

Evidence summaries: the evolution of a rapid review approach. Syst Rev

El-Sayed IH Endoscopic skull base and transoral surgery during COVID-19 pandemic: Minimizing droplet spread with negativepressure otolaryngology viral isolation drape

In vitro comparison of surgical techniques in times of the SARS-CoV-2 pandemic: electrocautery generates more droplets and aerosol than laser surgery or drilling. European archives of otorhino-laryngolog 2020

Reducing Aerosolized Particles and Droplet Spread in Endoscopic Sinus Surgery during COVID-19

Quantification of Aerosol Particle Concentrations During Endoscopic Sinonasal Surgery in the Operating Room

With thanks to Jordan Charlesworth, Viviana Finistrella and Kerry Broom at Public Health England for their assistance in handling the administration required to undertake this review.J o u r n a l P r e -p r o o f

Findings Evidence limitations / overlap