key: cord-0688653-pz95qupr
authors: Fleck, B. A.; Thornton, G. M.; Zhong, L.; Hartling, L. A.; Dandnayak, D.; Kroeker, E.; Fleck, N. J.
title: The impact of heating, ventilation, and air conditioning design features on the transmission of viruses, including the 2019 novel coronavirus: a systematic review of filtration
date: 2021-09-25
journal: nan
DOI: 10.1101/2021.09.23.21264025
sha: bf85224bf2b1bd6ad4fbc1f585cc6f0518e3858b
doc_id: 688653
cord_uid: pz95qupr

Historically, viruses have demonstrated airborne transmission. Emerging evidence suggests the novel coronavirus (SARS-CoV-2) that causes COVID-19 may also spread by airborne transmission. This is more likely in indoor environments, particularly with poor ventilation. In the context of potential airborne transmission, a vital mitigation strategy for the built environment is heating, ventilation, and air conditioning (HVAC) systems. HVAC features could modify virus transmission potential. A systematic review following international standards was conducted to comprehensively identify and synthesize research examining the effectiveness of filters within HVAC systems in reducing virus transmission. Twenty-three relevant studies showed that: filtration was associated with decreased transmission; filters removed viruses from the air; increasing filter efficiency (efficiency of particle removal) was associated with decreased transmission, decreased infection risk, and increased viral filtration efficiency (efficiency of virus removal); increasing filter efficiency above MERV 13 was associated with limited benefit in further reduction of virus concentration and infection risk; and filters with the same efficiency rating from different companies showed variable performance. Increasing filter efficiency may mitigate virus transmission; however, improvement may be limited above MERV 13. Adapting HVAC systems to mitigate virus transmission requires a multi-factorial approach and filtration is one factor offering demonstrated potential for decreased transmission.

Filtration and Virus Transmission 5 2016 in Europe, ISO 16890 replaced EN779 which classified filters as G1-G4; M5-M6; F7-F9. 10 EN779 had replaced Eurovent 4/9 which superseded Eurovent 4/5. 10 In ASHRAE Standard 52. , filter efficiency is based on particle size removal efficiency (PSE). 11 In other words, filter efficiency is the fraction of particles removed from air passing through the filter. 12 Particles fall into three size ranges: E1 0.30-1.0 µm; E2 1.0-3.0 µm; and E3 3.0-10.0 µm. The PSEs in these size ranges are used to determine the MERV rating, which ranges from MERV 1 to MERV 16. Another common filter is a High Efficiency Particulate Air (HEPA) filter; the filter efficiency of a HEPA filter is better than MERV 16. 12 Based on these dates, studies and recommendations may report a variety of filter efficiencies from EU, F, MERV, and HEPA.

In January 2021, ASHRAE 5 made recommendations for reducing airborne infectious aerosol exposure, which included the use of MERV 13 or higher filters for air recirculated by HVAC systems. When accessed in April 2021, the ASHRAE website indicated that MERV 13 is recommended but MERV 14 or better is preferred. 13 In March 2021, the WHO released a roadmap concerning indoor ventilation during COVID-19. 14 Based on a scoping review that identified six studies specific to SARS-CoV-2 and review of technical guidance by leading international HVAC organizations, the roadmap presents standards for healthcare, non-residential and residential environments based on type of ventilation (natural vs. mechanical). In specific situations (e.g., depending on ventilation rate and airflow patterns, system designs with air recirculation modes or heat recovery), HEPA or MERV 14 filters are recommended. 14 This systematic review considered whether virus transmission is affected by HVAC design features, particularly, filtration. In this review, an extensive and comprehensive search of the literature was conducted to identify and synthesize published research evaluating the effectiveness of filtration in reducing virus transmission. The insight drawn from this review could help answer . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

This systematic review addressed the research question: is virus transmission affected by HVAC design features, particularly, filtration? The current review was part of a larger research program to review literature on HVAC design features (ventilation, filtration, ultraviolet radiation, and humidity) and virus transmission. Results for other HVAC design features of interest are reported separately due to the volume and heterogeneity of the research. The systematic review is registered. 15 An a priori protocol was developed and is publicly available. 16 The standards for the conduct of systematic reviews defined by the international Cochrane organization 17 were followed with modifications for questions of etiology. 18 The review is reported according to accepted reporting standards. 19 Search Strategy. From inception to June 2020, three electronic databases (Ovid MEDLINE, Compendex, Web of Science Core) were searched by a research librarian (GMT) using concepts related to virus, transmission, and HVAC. The Ovid MEDLINE search strategy is detailed in Table 1 . Prior to implementing the searches, the strategies were peer-reviewed by two librarians (TL, AH). In January 2021, the search was updated. Reference lists of all relevant papers were screened, in addition to relevant review articles. Conference abstracts were identified through Compendex and Web of Science and were not included, but literature was searched to see whether any potentially relevant abstracts had been published as complete papers. Limits by year or language of publication were not placed on the search; however, only English-language studies . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 25, 2021. ; https://doi.org/10.1101/2021.09.23.21264025 doi: medRxiv preprint were included due to the volume of available literature and resource constraints. EndNote was used to manage references with duplicate records removed prior to screening.

Study Selection. Study selection had two stages. First, two reviewers independently screened titles and abstracts of references identified by electronic database searches. Relevance of each record was classified as Yes, Maybe, or No. Any conflicts between Yes/Maybe and No were resolved by one reviewer. To ensure consistency among the review team, pilot testing was conducted with three sets of studies (n=199 each). The review team met to discuss discrepancies and develop decision rules after each set of pilot screenings. Second, two reviewers independently reviewed full text articles and applied inclusion and exclusion criteria. Reviewers classified studies as Include or Exclude. Any conflicts between Include and Exclude were resolved by consensus of the review team. One reviewer resolved conflicts between different exclusion reasons. The second stage of screening was pilot tested with three sets of studies (n=30 each). The review team met to resolve discrepancies after each pilot round. The review team conducted screening using Covidence software.

Inclusion and Exclusion Criteria. Inclusion and exclusion criteria are listed in Table 2 . This systematic review was part of a larger effort to examine different HVAC design features and virus transmission. While all design features were included in the search and screening process at once, only studies evaluating filtration were synthesized here. A variety of agents were included in the search; however, studies of viruses or agents that simulated viruses were prioritized. Other agents (e.g., bacteria, fungi) would be included only if studies were not available that were specific to viruses. Studies using bacteriophages, which are viruses that infect bacterial cells, 20 were included. This review is interested in studies of the indoor built environment (e.g., office, public, residential buildings) which had mechanical ventilation. Primary research that provided quantitative results . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint (where available) were extracted, including any filter efficiency ratings or classifications (such as MERV and EU ratings or HEPA) or filter efficiencies expressed as percentages, where applicable. More recent filter efficiencies are based on ASHRAE Standard 52.2-2017 and represent particle size removal efficiencies (PSE) with particles falling into three size ranges: E1 0.30-1.0 µm; E2 1.0-3.0 µm; and E3 3.0-10.0 µm. 11 Efficiency of particle removal is usually represented by conventional filter . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 25, 2021. ; https://doi.org/10.1101/2021.09.23.21264025 doi: medRxiv preprint efficiency ratings, such as MERV, EU, F, and HEPA. Quantitative data were extracted, as well as results of any tests of statistical significance related to filtration features. The primary outcome of interest was quantitative measures of the association between filtration and virus transmission. As such, data on actual transmission were extracted where available (i.e., infections), as well as information regarding viruses, filters, setting and experimental test set-up, and outcomes. The distinction between the efficiency of particle removal described above and the efficiency of virus removal is important. The efficiency of virus removal is calculated as the difference between the virus concentration upstream of the filter and the virus concentration downstream of the filter divided by the virus concentration upstream of the filter expressed as a percentage. Only one aerosolized virus study used terminology that referred explicitly to virus, viral filtration efficiency, 26 while the remaining studies on virus removal used a variety of terms typical for particle removal: removal efficiency, 27 filtrating efficiency, 28 filter efficiency, 29 and filter reduction efficiency. [30] [31] European ratings were presented with MERV rating conversions. 32 Using a data extraction form spreadsheet to ensure comprehensive and consistent capture of data, one reviewer extracted data and a second reviewer verified data for accuracy and completeness. Any discrepancies were discussed by the review team.

Data Synthesis. As anticipated, meta-analysis was not possible due to heterogeneity across studies in terms of study design, filtration features examined, outcomes assessed, and reporting of results.

Evidence tables were developed to describe the studies and their results, as well as a narrative synthesis of the results. To allow for meaningful synthesis and comparison across studies, the studies are presented and discussed in three groups: animal studies (Table 3) , aerosolized virus studies (Table 4) , and modelling studies (Table 5) .

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Animal Studies (n=7). Six studies evaluated the influence of filtration on PRRSV in pigs [33] [34] [35] [36] [37] [38] and one study examined NDV in chickens. 39 Of the seven studies, three were performed using experimental test set-ups ups [33] [34] 39 and four were performed in the field (i.e., pig barns). [35] [36] [37] [38] Five of the seven studies found that filtration was associated with decreased virus transmission (Table 3) . 33, [35] [36] [37] 39 Pitkin et al 35 also found that filtration was associated with decreased daily risk of infections for PRRSV. One study found the use of filtration was associated with decreased . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. situations. As well, two studies found that filter performance varied by manufacturer when testing similarly rated filters from different companies. 34, 39 Aerosolized Virus Studies (n=7). Five of seven aerosolized virus studies found that filtration was associated with virus removal using PRRSV, 30 equine arteritis virus (EAV), 30 bovine enterovirus (BEV), 30 human adenovirus, 29 and the bacteriophages T7 27-28 and MS2. 31 One study found that increasing MERV rating was associated with decreasing virus concentration for bacteriophage T4 40 at different locations within an apartment unit, and another found that increasing MERV rating was associated with increasing viral filtration efficiency using bacteriophage MS2 26 in a test duct set-up (Table 4) .

Like the animal studies conducted by Dee et al 33 and Hopkins and Drury, 39 two aerosolized studies found increasing MERV ratings to be associated with increased virus removal efficiencies. 26, 40 Zhang et al 26 noted that the filter efficiency associated with E1 (i.e., 0.30-1.0 µm; the smallest particle size range for MERV classification) was a good approximation of the viral filtration efficiency. In addition, Washam et al, 27 prior to the use of MERV ratings as developed in 1999, identified cost differences between filters of similar efficiency.

Modelling Studies (n=9). Nine of the filtration studies were modelling, employing the following models: one-dimensional analytical model, 41 Wells-Riley model, 42-45 CONTAM multi-zone IAQ . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint From the nine modelling studies, five studies found that increasing filter efficiency associated with decreased virus concentration 41,46 and decreased risk, including absolute risk and relative risk of infection, 42 transmission risk, 44 and infection risk 48 (see Table 5 ). One study found that the use of filtration was associated with decreased attack rate. 43 Of the nine modelling studies, four evaluated the use of a single filter 43,45,48-49 ; all agreed that installing a filter is more beneficial than not installing a filter. Like the experimental studies of Dee et al 36 and Spronk et al, 37 and three modelling studies comparing single filters 41-42,46 agreed that there is a threshold beyond which increasing filter efficiency may not affect the probability of infection. One study using a MERV 8 prefilter was able to model a difference in virus . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (Table 6 ). Two experimental studies had low risk of bias for selection bias and confounding but had unclear risk of bias for information bias because of a lack of clarity in the methodological details. [28] [29] Seven of the nine modelling studies had low risk of bias for all three domains: definition, assumption, validation (Table 7) . Two modelling studies had low risk of bias for assumption and validation but had unclear risk of bias for definition because of a lack of clarity about the HEPA filter efficiency 45 and contribution of fresh air. 49

While there is substantial literature on the use of filters to remove particles, this review was designed to consider the use of filters to remove viruses. The 23 articles that satisfied our strict criteria revealed several important findings. First, filtration was associated with decreased virus transmission. Second, filters removed viruses from the air. Third, increasing filter efficiency . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 25, 2021. ; https://doi.org/10.1101/2021.09.23.21264025 doi: medRxiv preprint (efficiency of particle removal) was associated with decreased transmission, decreased infection risk, and increased viral filtration efficiency (efficiency of virus removal). Fourth, increasing filter efficiency above MERV 13 was associated with limited benefit in further reduction of virus concentration and infection risk. Fifth, filters with the same filter efficiency rating from different companies had varied performance regarding transmission in animal studies.

Implications for Research. The modelling studies spanned from 2009 to 2020 and the aerosolized virus studies spanned from 1966 to 2021; some of the more recent studies were motivated by the COVID-19 pandemic. Many viruses were examined; however, it is particularly interesting that there were only two coronavirus studies (both SARS-CoV-2) for filtration, both modelling, and only one aerosolized study that used MS2 as a potential surrogate for SARS-CoV-2 based on size. 26 Additionally, one of the studies 49 discussed the implications of filtration in relation to SARS-CoV-2 but used influenza to set relevant infectivity parameters. The limited number of coronavirus (and specifically SARS-CoV-2) studies suggests a potential research gap to be addressed in the future.

There is a very rich body of literature of engineering or laboratory studies which focuses on collecting physical metrics expected to affect transmission; these were not considered in this search as our focus was on connecting transmission itself with installed equipment. The trade-off between isolating specific parameters related to filtration physics or analysing more combined links in the chain of transmission is an important consideration and we stress that the literature gaps tend to be in studies which consider systems holistically. This points to a need for interdisciplinary studies which combine knowledge of well controlled filter experiments with less well controlled "real world" situations which inherently capture combined synergies in the transmission chain as well as possible "unknown unknowns" in that chain.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint Interestingly, the animal studies only spanned from 1971 to 2013. Furthermore, no field studies examining potential mitigation of virus transmission in humans using filtration were found. This suggests a research opportunity to investigate the use of filtration on mitigating virus transmission in "real-world" built environments occupied by humans, as well as epidemiological studies during disease outbreaks. Taken together, these findings identify an opportunity for more research that investigates HVAC filtration mitigation of human viruses and, specifically, human coronaviruses.

More recent aerosolized virus studies use the ASHRAE Standard 52.2 test duct. 26, 31 This establishes an important level of consistency for future research. The aerosolized virus studies that state an explicit interest in SARS-CoV-2 used the bacteriophage MS2, which has a smaller size than SARS-CoV-2. Future research could explore the ramifications, if any, of this size differential on virus transmission given the size of droplet or droplet nuclei in which the virus itself is suspended.

Implications for Practice. Some findings are straightforward to address in practice. For example, proper installation is required for a filter to be effective in removing virus and preventing transmission. 39 Other findings are challenging to address in practice. Two studies documented variations in the performance of similarly rated filters that were purchased from different manufacturers. 36, 39 Variations in performace can occur in filters with the same MERV rating from the same manufacturers, not just different manufacturers. This alone implies that within the broad criteria of MERV ratings, there is enough variation in performance to point to a need for more filter sub-ranges or more stringent testing methods of MERV value.

A practical benchmark emerging from this review was, from the findings of Zhang et al, 26 that a conservative estimate of the viral filtration efficiency could be approximated by the E1 efficiency used to determine MERV rating in ASHRAE Standard 52.2-2017.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint Not surprisingly, increasing filter efficiency, whether based on increasing filter efficiency before MERV ratings were established, 39 increasing MERV rating, 42 or increasing from MERV to HEPA, 34 was associated with mitigation of virus transmission. An important practical consideration is that the improvement is limited above the filter efficiency MERV 13. This concept of diminishing returns was documented in both animal studies [36] [37] and modelling studies. [41] [42] 46 Spronk et al 37 Diminishing returns are not limited to MERV ratings as Washam et al, 27 prior to the use of MERV ratings, found that similar efficiency can be achieved using a lower cost option. In addition, the cost increases with increasing MERV rating and HEPA filtration relative to the cost for MERV 13; however, the cost of filtration for these filters remains less than the cost of outdoor air ventilation with the equivalent transmission reduction. 42 This finding is consistent with current ASHRAE recommendations for reducing airborne infectious aerosol exposure. 12 Interestingly, ASHRAE indicates that MERV 13 is recommended but MERV 14 is preferred. 13 The use of MERV 14 is supported by WHO in the context of COVID-19. 14 Installing or upgrading an air filtration system can sometimes be an expensive intervention.

However, illness costs money as well and there is considerable research available showing simply how improved indoor air quality (IAQ) infrastructure investment is profitable when building . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Some studies have shown that there can be a plateau in effectiveness for filters past MERV 13 in typical situations 42,46 . Mazumdar and Chen 41 found that a 94% efficiency filter would not be able to protect passengers sitting far away from the infectious source in an airliner cabin and that a 99.9% filter was needed for their application. They go on to state that further increase in filter efficiency might be difficult and its effectiveness not clear. All filters with the same rating are not equal either. Differences in the filter media or frame design across companies and inconsistency in the filter rating systems across countries can contribute to discrepancies in filter efficiency 34 .

The source of the raw material of the filter media can also impact filter quality 35 . Zhang et al 26 found that the viral filtration efficiency (VFE) is generally correlated with the MERV rating but they are not the same. They found that the VFE is always higher than E1, but lower than E2 or E3 efficiencies. This is all to say that choosing the right filter for the right application is important.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The location, use case, existing system, budget, and acceptable level of risk should be taken into account when considering air filtration systems 33, 36, 37 .

When considering scientific testing of filters, the size of the aerosol challenge should be considered very carefully. Many studies have stated that the level of contamination in their experiments was probably much larger than what would be expected in their respective typical situations 27, 34, 39, 40 .

This could lead to certain interventions being wrongfully deemed inadequate. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted September 25, 2021. ; https://doi.org/10.1101/2021.09.23.21264025 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint Transmission -Transmission in 0/10 pigs in HEPA filtration group significantly lower than transmission in low-cost filtration group (4/10 pigs) and no filtration group (9/10 pigs).

-Transmission in low-cost filtration group significantly lower than no filtration group.

-Filtration associated with decreased transmission.

-Increasing filter efficiency associated with decreasing transmission. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. HEPA filtration is associated with decreased risk of infection . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 25, 2021. ; https://doi.org/10.1101/2021.09.23.21264025 doi: medRxiv preprint 27 low low low Hopkins (1971) 39 low low low Dee (2006) 33 low low low 34 low low low 35 low low low Malaithao (2009) 28 low unclear low Spronk (2010) 37 low low low Dee (2011) 36 low low low Alonso (2013) 38 low low low Kunkel (2017) 40 low low low Wenke (2017) 30 low low low Bandaly (2019) 29 low unclear low Zhang (2020) 26 low low low Vyskocil (2021) 31 low low low * Confounding assessed for our comparison of interest. 45 unclear low low . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 25, 2021. ; https://doi.org/10.1101/2021.09.23.21264025 doi: medRxiv preprint Figure 1 . Flow of studies through the selection process (note: search was conducted for all HVAC design features but only studies of filtration are included in this manuscript)

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 25, 2021. ; https://doi.org/10.1101/2021.09.23.21264025 doi: medRxiv preprint

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