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Aerosol Generating Procedures Research Prioritisation Report


Executive Summary

Uncertainties about infective risk associated with Aerosol-Generating Procedures (AGPs) and broader questions about airborne transmission of SARS-CoV-2 in healthcare settings continue to impact negatively on provision of care in the NHS and other care facilities. In response to a relative lack of interdisciplinary research addressing key questions about AGP risk and its mitigation, the NIHR Clinical Research Network AGP Research Group and Independent high-risk AGP Panel convened a Research Prioritisation Exercise involving experts from Aerosol Science, Engineering, Virology and Aerobiology, Infection Prevention & Control, as well as multiple medical and dental disciplines.

The five most important areas for research prioritisation and funding were highlighted by the multidisciplinary group:

Fundamental aerobiology, including virus distribution and viability in airborne particles.

● Understanding risk factors for transmissibility in order to quantify risk taking into account multiple domains (patient, procedure, place [environment], pathogen [to include SARS-CoV-2 variants of concern], and the healthcare professional).

● Identifying which mitigating precautions and their components are important:
To include clinical efficacy testing of Personal Protective Equipment (PPE), environmental measures (eg. ventilation, filtration), and other barrier devices.

● Investigation of the contribution of inhalation (across the particle size spectrum) versus inoculation (fomites) for transmission of SARS-CoV-2 and other pathogens related to AGPs and other healthcare interventions.

Understanding infective risk perception, behaviours and acceptability of mitigation strategies of healthcare workers, patients and the public.

The Expert Group also made several research methodology recommendations including the absolute need for standardisation of methodology for physical and biological measurements of aerosols, which would facilitate comparative studies and infection modelling, and the need for core infrastructure to enable experimental and clinical airborne transmissibility research.

The framework provided by these research priorities and research methodology recommendations will support commissioning and funding of AGP and broader airborne transmissibility research across the translational research spectrum from basic science to applied health research.


The National Institute for Health Research (NIHR) has played a critical role in the fight against COVID-19, funding and delivering ground-breaking research that is already helping to save lives in the UK and around the world.

Aerosol Generating Procedures (AGP) are considered to be any medical, dental or patient care procedure that results in the production of an aerosol (a suspension in air of liquid particles of varying size [typically <20 micron]). The World Health Organisation (WHO) has defined medical procedures that have been reported to be aerosol-generating and consistently associated with an increased risk of pathogen transmission as ‘high-risk’ AGPs.

Categorisation of procedures as a high-risk AGP has impacted on NHS delivery and costs during the COVID-19 pandemic with the requirement of additional ‘airborne’ Personal Protective Equipment (PPE) and implementation of fallow time post-procedure. Lack of clarity about infective risk associated with AGPs and the best way to mitigate risk continues to impact negatively on waiting lists and clinical outcomes. Perceived infective risk associated with AGPs has created uncertainty and anxiety in healthcare workers and patients. The contribution of high-risk AGPs to nosocomial infections remains unclear.

The current UK Four Nations COVID-19 Infection Prevention and Control guidance includes a list of procedures classified as AGPs, the evidence for which is largely based on limited clinical evidence from previous respiratory virus outbreaks, with little underpinning good-quality science.

The NIHR AGP Research Group was convened in 2020 by the NIHR Urgent Public Health (UPH) Group in order to scope ongoing clinical AGP research, bring together individual projects and teams across basic science, medical and dental disciplines, as well as facilitate research delivery and ensure a pathway to impact, in the context of the COVID-19 pandemic.

In January 2021, the UK Independent High-risk AGP Panel published a summary of recommendations on a restricted number of healthcare interventions that had been suggested as high-risk AGPs, highlighting the dearth of evidence with which to define individual procedures as aerosol-generating and/or high risk.

The NIHR AGP Research Group and Independent High-risk AGP Panel have both concluded that rapid advances in understanding of risk and mode of transmission of SARS-CoV-2 infection from AGPs (and other interventions in healthcare settings), leading to meaningful impact on clinical outcomes and delivery, would need commissioning of a dedicated multidisciplinary effort to coordinate research across the translational research spectrum from basic physical and biological studies through to applied health research.

This Research Prioritisation Exercise, which was hosted by the NIHR Clinical Research Network (CRN) on Thursday 22nd April 2021 and convened by the NIHR AGP Research Group and the Independent High-risk AGP Panel, represents the first step in increasing interdisciplinarity and highlighting the gaps in the evidence base to research commissioners and policy-makers. Experts from the full range of underpinning scientific disciplines, including aerosol science, fluid dynamics, environmental engineering, virology and aerobiology, joined colleagues from Infection Control and multiple medical/dental disciplines, in order to align research priorities and define research gaps.

Delegate numbers were restricted in order to facilitate detailed discussion between attendees in a virtual one-day format, in the expectation that the output would subsequently be available for wider consultation.

Five AGP Research Priorities

The following are the five most important specific research priorities that emerged from the two-stage, multidisciplinary, small-group breakout sessions and a subsequent plenary discussion.

Fundamental Aerobiology

Attendees felt that a detailed understanding of the aerobiology of the SARS-CoV-2 virus underpinned all other aspects of research targeted at reducing the risk associated with healthcare interventions, and also remained key to delineating the contribution of airborne (particularly short-range) transmissibility to SARS-CoV-2 infectivity. Although the Exercise focussed on SARS-CoV-2, the importance of fundamental aerobiology research for known and future infectious diseases was recognised.

In parallel, the attendees recognised that, historically, aerobiology research has lagged behind other basic and applied aerosol research work, perhaps related to the technical demands of air sampling, especially in ‘real life’ healthcare settings, and relative lack of model systems.

The breakout groups highlighted a series of specific key questions about:

● virus distribution and viability (dose) across the spectrum of airborne particle sizes.
● decay in pathogen viability over time in different environmental conditions.
● the natural history of virus emission before and during the COVID-19 illness and in asymptomatic individuals.
● how virus emission (and transmissibility) compares between healthcare interventions, including named AGPs, and respiratory activities such as cough and talking.

Risk Factors for Transmissibility

The need to determine clinically applicable risk factors for transmissibility/infective risk related to healthcare interventions in order to develop a multivariate model to stratify risk for appropriate mitigation was considered a key research priority. The attendees highlighted multiple factors across several domains that likely contribute to infectious risk and outcomes associated with AGPs (and with wider applicability to other environments and behaviours) including the five Ps: Patient; Procedure; Place (environment); Pathogen; Healthcare Professional.

The attendees emphasised that much basic research was still required in order to quantify risk in each domain but that appropriate multidisciplinary expertise should be in place to develop and evolve a clinical risk model for immediate validation and effectiveness testing.

Which Mitigating Precautions and their Components are Important?

The need for immediate research into effective mitigation of infective risk associated with AGPs was prioritised by the Exercise. The paucity of clinical efficacy and effectiveness testing for Personal Protective Equipment (PPE), environmental measures (eg. ventilation, filtration), and other barrier devices, to date, was noted. Groups felt that ‘mechanistic’ research into how individual mitigations reduce airborne particles (including aerosol), and into which components of equipment/devices are critical for protection, is important (for example, do FRSMs protect against aerosol emission/exposure?). The relative lack of research on environmental interventions such as High Efficiency Particulate Air (HEPA) filtration and UltraViolet (UV) exposure in healthcare settings needs addressing.

The attendees also highlighted the importance of a parallel stream of implementation research about interventions proven to mitigate infective risk in healthcare settings (see below).

Transmission of SARS-CoV-2 and other Pathogens

Attendees acknowledged that major questions about the contribution of inhalation (aerosol versus droplets) versus inoculation (fomites) for COVID-19 risk associated with AGPs and other activities/behaviours continue to hamper correct stratification of procedures as ‘high risk’ and their mitigation in different healthcare settings. Gaps in the evidence base have been highlighted even more by recent findings, which suggest that some AGPs do not generate physical aerosols in excess of those generated by respiratory activities such as cough, blurring the established distinction between defined ‘high-risk’ AGPs and risk in other non-procedural healthcare settings.

The relative lack of experimental methods with which to quantify aerosols and other particles (particularly in the 10-100 micron range) across the continuum of airborne particle size in healthcare environments was highlighted.

Understanding Infective Risk Perception, Behaviours and Acceptability of Mitigation Strategies

This research area, which includes widespread engagement and consultation with patients and the public, as well as multiple constituent healthcare professional groups (and their professional organisations), and the behavioural science of risk perception, was not represented in the framework seventeen questions that delegates were given. However, the critical importance of this research area was consistently highlighted throughout the exercise.

It was widely recognised that patients/public and multiple healthcare professional groups in different healthcare settings will have widely different priorities about procedure-related risk, which would require a complex and detailed piece of work to capture and understand in order to design and deliver the best clinical AGP research.

It is noted that these research priorities overlap with the AGP research needs highlighted by the WHO COVID-19 IPC R&D Expert Group in 2020 and the German Association for Aerosol Research.

Research Methodology Recommendations

Research feasibility and methodology questions

  1. Is core research infrastructure (eg. bioaerosol chambers/procedure models) required?
  2. In the absence of SARS-CoV-2-infected patients, what is the best model system for studying aerobiology?
  3. Is standardised methodology for physical and biological measurement of aerosols desirable and deliverable in clinical settings?
  4. What complementary methods can be used simultaneously to measure particles across the size spectrum?
  5. Are traditional randomised controlled trials acceptable and feasible for high-risk AGP research, particularly mitigation approaches?
  6. What approach(es) can be used to harness the power of genomic viral sequencing to assess exposure and infective risk in healthcare settings?
  7. Is a systematic review of AGP IPC evidence worthwhile given the paucity of evidence to date?
  8. How do we avoid duplication of effort, particularly from an international standpoint?

Multidisciplinary group responses to the eight research feasibility and methodology questions are noted below. Questions #3 and #4 were combined by three of the four groups. Although viral genomic sequencing has played a key role in understanding and managing the COVID-19 pandemic, the Groups felt that it would currently have only an indirect role in AGP research (question #6) at the present time, but it could become a key AGP research tool if genomic analysis of healthcare infection outbreaks could be mapped to individual healthcare worker exposures.

Standardisation of methodology for physical and biological measurements of aerosols

This was considered the key overarching priority to advance the research field, allowing comparison of data across different procedures and settings (experimental models and ‘real life’ healthcare settings) from different research groups. The critical importance of combining physical measurements with aerobiology endpoints was highlighted. Standardisation of methodology would enable data merging for clinical risk model development. The importance of an agreed methodological framework and collaboration between scientific disciplines to translate findings to computational fluid dynamic models was highlighted.

A consensus definition of key measurable parameters, with reference to calibration events (for example, tidal breathing or cough), was felt to be integral to establishing standardised methods.

The artificial distinction between aerosol and droplet particles was considered. A framework of complementary methods is needed for accurate sizing and capture of particles, with good temporal resolution, using complementary physical measurements that can be applied to the
clinical setting.

The need for core infrastructure to enable experimental and clinical airborne transmissibility research

The importance of experimental modelling in a dedicated bioaerosol chamber and other carefully controlled experimental settings was acknowledged. However, attendees considered that the establishment of one or more ‘AGP rooms’ should be considered strongly, to allow ‘real-life’ aerosol measurements and air sampling with minimal disruption to clinical activity during healthcare interventions. Attendees with experience of physical aerosol measurements and air sampling in clinical settings during the COVID-19 pandemic, to date, highlighted the haphazard nature and practical difficulty of identifying cases and then
setting up equipment, in real-time, even when linked to other clinical intervention trials.

A network of one or more experimental chambers and clinical infrastructure would facilitate parallel physical and aerobiology studies, as prioritised above.

Model systems for studying the aerobiology of transmissibility

Workshop attendees discussed the requirement for experimental models and surrogate endpoints with which to study infectivity relevant to healthcare environments, in the absence of SARS-CoV-2-infected patients, and for future preparedness. This enabling technology could allow prospective development of strategies to mitigate airborne infectious risk in advance of future outbreaks. Several options were discussed including ‘challenge’ studies, use of non-pathological ‘tracers’ (e.g bacteriophage) or respiratory tract commensal organisms as a surrogate biomarker of viable virus, all of which need experimental validation.

Randomised clinical trial evaluation of mitigation approaches

Although attendees acknowledged the large evidence gaps in the underpinning science about airborne infection risk and mechanism of action of mitigating devices and behaviours in healthcare settings, it was felt that high quality pragmatic clinical trials, which test efficacy and effectiveness of interventions, should occur without delay. These could include evaluation of PPE items, ‘environmental’ interventions including air filtration and ventilation, as well as other barrier devices. The major interest of, and opportunities to work with, the commercial sector was noted. The need for methodological expertise in device evaluation, as well as in adaptive and complex intervention trial design, was highlighted, allowing
ongoing studies to be responsive to new insights into transmissibility, risk modelling and variable infection rates.

The critical role of healthcare workers, patients and the public in design, acceptability and delivery of clinical research studies was highlighted.

Living systematic review of AGP evidence

Attendees identified the need to perform rigorous, systematic review of the existing data on procedures currently listed as AGPs, without delay. This should include aerosol characterisation work and aerobiology considerations, in parallel with the clinical and epidemiological evidence, in order to provide even more focus on the gaps in the evidence, to re-consider definition of procedures currently listed as ‘aerosol-generating’ and ‘high risk’, as well as assess risk associated with other healthcare interventions.

Continuous update was felt to be mandatory.

The importance of careful framing of the questions to be addressed by research synthesis was highlighted, as was the need for a multi-disciplinary approach to include a broad range of clinical expertise in parallel with methodologists.

Coordination of the national and international research effort on airborne transmissibility and infective risk for COVID-19 and future pathogens

This was felt to be essential to enable the multi-disciplinary research and subsequent clinical translation necessary for maximum clinical impact. There is no formal national or international registry of AGP research, with which to understand who is doing what. Although some duplication of research is desirable to allow confirmation and validation, particularly in different healthcare settings and systems, it was considered that better coordination is required to share methodology and protocols at national and international level.

Concluding Remarks

The recommendations expressed in this report are based solely on those that emerged during the Research Prioritisation Exercise and do not necessarily represent the opinion of the organisations, to which attendees are affiliated. This report is expected to support dialogue with NIHR and DHSC regarding future research opportunities.

Subsequently, the NIHR AGP Research Group has begun work with the NIHR CUE-TIP Panel to develop a framework to facilitate high quality consultation on airborne transmissibility in healthcare settings with diverse healthcare professional groups, patients and the public.

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