key: cord-0293623-ejc1iwax
authors: Thornton, G. M.; Fleck, B. A.; Kroeker, E.; Dandnayak, D.; Fleck, N.; Zhong, L.; Hartling, L. A.
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 ventilation and coronavirus
date: 2021-10-11
journal: nan
DOI: 10.1101/2021.10.08.21264765
sha: e3077d464fda74b4f2e44034cc24e3c94c1f88b5
doc_id: 293623
cord_uid: ejc1iwax

Aerosol transmission has been a pathway for virus spread for many viruses. Similarly, emerging evidence regarding SARS-CoV-2, and the resulting pandemic as declared by WHO in March 2020, determined aerosol transmission for SARS-CoV-2 to be significant. As such, public health officials and professionals have sought data regarding the effect of Heating, Ventilation, and Air Conditioning (HVAC) features to control and mitigate viruses, particularly coronaviruses. A systematic review was conducted using international standards to identify and comprehensively synthesize research examining the effectiveness of ventilation for mitigating transmission of coronaviruses. The results from 32 relevant studies showed that: increased ventilation rate was associated with decreased transmission, transmission probability/risk, infection probability/risk, droplet persistence, virus concentration, and increased virus removal and virus particle removal efficiency; increased ventilation rate decreased risk at longer exposure times; some ventilation was better than no ventilation; airflow patterns affected transmission; ventilation feature (e.g., supply/exhaust, fans) placement influenced particle distribution. Some studies provided qualitative recommendations; however, few provided specific quantitative ventilation parameters suggesting a significant gap in current research. Adapting HVAC ventilation systems to mitigate virus transmission is not a one-solution-fits-all approach but instead requires consideration of factors such as ventilation rate, airflow patterns, air balancing, occupancy, and feature placement.

Increasing ventilation, whether through ventilation rates (ACH, m 3 /h, m 3 /min, L/min) or as determined by CO2 levels (ppm), is associated with decreased transmission, transmission probability/risk, infection probability/risk, droplet persistence, and virus concentration, and increased virus removal and efficiency of virus particle removal. As well, professionals should consider the fact that changing ventilation rate or using mixing ventilation is not always the only way to mitigate and control viruses as varying airflow patterns and the use of ventilation resulted in better outcomes than situations without ventilation. Practitioners also need to consider occupancy, ventilation feature (supply/exhaust and fans) placement, and exposure time in conjunction with both ventilation rates and airflow patterns. Some recommendations with quantified data were made, including using an air change rate of 9 h -1 for a hospital ward; waiting six air changes or 2.5 hours before allowing different individuals into an unfiltered office with ~2 fresh air changes (FCH) and one air change for a high-efficiency MERV or HEPA filtered laboratory; and using a pressure difference between -2 and -25 Pa in negative pressure isolation spaces. Other recommendations for practice included using or increasing ventilation, introducing fresh air, using maximum supply rates, avoiding poorly ventilated spaces, assessing fan placement and potentially increasing ventilation locations, and employing ventilation testing and air balancing checks. Coronavirus has emerged as an infectious agent of great concern for potential airborne transmission.

HVAC systems can reduce airborne virus exposure through dilution or removal of contaminated air inside the building envelope where humans breathe. 7, [9] [10] [11] Virus transmission can be influenced by various HVAC design features, including ventilation, filtration, ultraviolet radiation, and humidity. Previous systematic reviews that examined HVAC systems and airborne transmission of infectious agents highlighted the need to quantify the HVAC parameters to minimize transmission. Li et al 9 found sufficient evidence to demonstrate an association between transmission of infectious agents and ventilation rate and/or airflow pattern. However, Li et al 9 found insufficient evidence to specify and quantify the minimum ventilation requirements in buildings in relation to the airborne transmission of infectious agents. Similarly, Luongo et al 7 demonstrated an association between increased infectious illness and decreased ventilation rate; however, insufficient data were found to quantify how mechanical ventilation may affect the airborne transmission of infectious agents. Furthermore, a recent review by Shajahan et al 12 reinforced the need to quantify the optimum range for HVAC parameters considering airborne exposure. At this time, what remains unknown is the specific quantity of any particular HVAC design feature that is effective in reducing virus transmission.

The current systematic review examined whether virus transmission is affected by HVAC design features, particularly, ventilation. In this review, published research evaluating the effectiveness . 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 preprint this version posted October 11, 2021. ;  https://doi.org/10.1101/2021. 10 .08.21264765 doi: medRxiv preprint of ventilation in reducing coronavirus transmission was examined. The insight drawn from this review could help answer questions of the utility of ventilation to mitigate the transmission of SARS-CoV-2 in mechanically ventilated indoor environments. Further, understanding effectiveness relative to ventilation rate and airflow patterns could inform control measures.

As an integral part of a larger research program to identify and synthesize the scientific literature on airborne virus transmission and HVAC design features, this systematic review focused specifically on the impact of ventilation on coronavirus transmission. Owing to the volume and heterogeneity of the published research, results for the impact of the other HVAC design features of interest on virus transmission are reported elsewhere. The a priori systematic review protocol is publicly available 13 and the systematic review is registered. 14 The review adheres to the standards for the conduct of systematic reviews defined by the international Cochrane organization 15 with modifications for questions related to etiology, 16 and the accepted standards for reporting. 17 

Using concepts for virus, transmission, and HVAC, a research librarian (GMT) searched three electronic databases (Ovid MEDLINE, Compendex, Web of Science Core) from inception to April 2020 with an update in January 2021. Search strategies were peer reviewed by two librarians (TL, AH) prior to implementing the searches; for example, the search strategy for Ovid MEDLINE is provided in Table 1 . Screening of reference lists of all relevant papers as well as relevant review articles was undertaken. Conference abstracts, identified through Compendex and Web of Science, . 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)

The copyright holder for this preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint were not included but searches were conducted to identify whether any potentially relevant conference abstracts had been published as peer-reviewed journal articles. Year and language limitations were not used in the search. Due to the volume of available literature and resource constraints, in the end, only English language studies were included. EndNote was utilized to manage records and duplicate records were removed prior to screening.

Title and abstract screening and full text review were the two stages of study selection. First, the titles and abstracts of all references identified by the electronic databases searches were screened by two reviewers independently. Each record was classified based on relevance as Yes, Maybe, or No. One reviewer resolved conflicts between Yes/Maybe and No. After each round of pilot testing using three sets of studies (n=199 each), the review team met to discuss discrepancies and develop decision rules. Second, the full text articles were reviewed and the inclusion and exclusion criteria were applied by two reviewers independently. Each study was classified as Include or Exclude.

Consensus of the reviewers resolved conflicts between Include and Exclude. One reviewer resolved conflicts between different exclusion reasons. After each round of pilot testing with three sets of studies (n=30 each), the review team met to resolve discrepancies. These two stages of study selection were conducted using Covidence software.

The inclusion and exclusion criteria used in this review are provided in Table 2 . Given that this systematic review was part of a larger research program to examine virus transmission and different HVAC design features, searching and screening for all HVAC design features was conducted at once; however, only studies evaluating ventilation were synthesized in this paper.

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The copyright holder for this preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint Likewise, searching and screening considered a variety of agents (e.g., bacteria, fungi) but prioritized studies of viruses or agents that simulated viruses. For this specific review, the synthesis was further narrowed from viruses to coronaviruses. Studies of the indoor built environment (e.g., office, public, residential buildings) with mechanical ventilation were of interest. Primary research with quantitative results of correlation or association between ventilation and coronavirus transmission was included. English-language, peer-reviewed publications were included with no limitation on year of publication.

Different risk of bias assessments were used for experimental and modelling studies. Risk of bias for experimental studies considered three domains: selection bias, information bias and confounding. 18, 19 Each domain was assessed as low, high, or unclear risk of bias using signaling questions 20 from guidance documents for the different study types, e.g., animal studies, laboratory experiments, epidemiological studies. [18] [19] 21 Risk of bias for modelling studies considered three domains: definition, assumption, and validation. 21, 22 For the modelling studies, definition evaluated model complexity and data sources, assumption evaluated the description and explanation of model assumptions, and validation evaluated model validation and sensitivity analysis. 22 Each domain was assessed as low, high, or unclear risk of bias using signaling questions. [21] [22] [23] After pilot testing among three review authors, the risk of bias was assessed by three reviewers (EK, DD, NF) independently and discrepancies were resolved by the review team.

General information was extracted regarding the study (authors, year of publication, country of corresponding author, study design) and methods (setting, population [as applicable], agent . 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)

The copyright holder for this preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint studied, intervention set-up). Details on ventilation parameters were extracted, including ventilation rate and airflow pattern. Ventilation rate may be expressed as air changes per hour (ACH), ventilation flow rates (m 3 /h, m 3 /min, L/min), ventilation usage (ventilation versus no ventilation), or as determined by CO2 levels (ppm). Quantitative data were extracted as well as results of relevant tests of statistical significance related to ventilation. The primary outcome of interest was quantitative measures of the association between ventilation and coronavirus transmission. Data were extracted on actual coronavirus transmission where available (i.e., infections), as well as virus removal, virus concentrations, particle dispersion, and particle persistence, probability of transmission and transmission risk (referred to as transmission probability/risk) and infection risk, infection transmission probability, infection probability, probability of infection, individual risk, and infection index (referred to as infection probability/risk) as applicable. Information regarding ventilation feature placement, supply/exhaust ratios, occupancy, filtration usage (as provided), and air balancing was also extracted. Employing a data extraction form spreadsheet to ensure comprehensiveness and consistency, one reviewer extracted data and a second reviewer verified data for accuracy and completeness. Discrepancies were discussed by the review team.

Due to heterogeneity across studies in terms of study design, ventilation features examined, outcomes assessed, and results reported, meta-analysis was not possible as anticipated. Evidence tables describing the studies and their results were developed. Narrative synthesis of the results of relevant studies was provided alongside evidence tables describing the studies and their results.

To facilitate meaningful synthesis and comparison across studies, studies were separated into three groups: ventilation use, airflow pattern, and ventilation rate and airflow pattern.

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The copyright holder for this preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint Results 12,177 unique citations were screened, where 2,428 were identified as potentially relevant from the title and abstract screening and 568 met the inclusion criteria ( Figure 1 ). Of the 568, 332 were relevant to ventilation. Of the 332 relevant to ventilation, 217 were relevant to viruses and, of those, 32 were relevant to coronaviruses ( Figure 1 ). Two of these relevant studies were related [24] [25] and are considered as one in the following syntheses. Attempts were made to divide studies into tables examining ventilation rate or airflow pattern. Most studies examining both ventilation rate and airflow pattern were challenging to separate into either individual category and a third (Table 4) , and five investigated the combined effect of ventilation rate and airflow patterns (Table 5) 

Twenty studies, including modelling (n=16), experimental (n=3), and observational (n=1) studies, analyzed the effect of ventilation rate on SARS-CoV-2/COVID-19 (n=16), SARS-CoV/SARS (n=3), and MERS-CoV (n=2) (see Table 3 ). Scenarios in the studies represented a wide range and variety of settings, including hospitals, 27-33 schools, 27,34 dental . 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)

The copyright holder for this preprint this version posted October 11, 2021 Of the 16 modelling studies analyzing ventilation rate, six studies found that increased ventilation, i.e., increased ACH, was associated with decreased transmission, 27 virus concentration, 31 probability of infection, 36 infection risk, 29,37 and risk of cross infection. 44 Two modelling studies found that increased ACH increased the efficiency of particle and virus removal. 26,28 Shao et al 26 also found that increasing ventilation by using increased ventilation settings (i.e., more ventilation sites) was also effective in particle removal. Additionally, four modelling studies found that increasing ventilation rate (m 3 /h and m 3 /min) was associated with decreased infection probability, 34,39 risk of airborne transmission, 42 and infection index ƞ. 33 Sun et al 39 also found that reduced occupancy was associated with lower minimum ventilation requirements. Kennedy et al, 45 when comparing no ventilation scenarios to ventilation scenarios, found that increased ventilation rate, through the use of ventilation systems, was associated with decreased infection risk.

Similarly, Miller et al, 41 although not using a specified metric, determined that increased ventilation rate, which led to a subsequent decrease in viral aerosol loss rates, was associated with decreased probability of infection.

Two modelling studies analyzed ventilation rate using CO2 levels as an indicator of ventilation rate. Both studies found that increased ventilation rate was associated with decreased CO2 levels and, as a result, decreased infection transmission probability 35 and transmission. 27 Two other modelling studies explored the impact of ventilation rate on individual risk and exposure times. 32, 34 Both found that increasing ventilation rate (measured as ACH or m 3 /h) was associated with longer . 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)

The copyright holder for this preprint this version posted October 11, 2021 . 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. Two studies that retroactively analyzed separate COVID-19 outbreaks in restaurants found that airflow pattern was an essential factor in the transmission of the virus. [24] [25] 47 Only one study provided quantified recommendations 49 ; four studies provided recommendations without quantification. 24 In addition, Li et al 51 found that downward ventilation provided a greater reduction in the . 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 preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint dispersion of the virus particles compared to mixing ventilation in the imbalanced airflow case.

Lim et al 52 found that air supplied from the room boundary and exhausted in the center of the room provided a greater reduction in the dispersion of the virus particles compared to the inverse case in both balanced and imbalanced airflow cases. In agreement with Li et al, 51 who found a small effect of airflow balancing on virus particle concentration and dispersion, Chen et al 53 similarly determined that airflow balancing had a relatively small to no effect on the dispersion of virus particles in the hospital ward, which was simulated using multi-zone modelling.

Satheesan et al 54 found that increasing the ventilation rate greatly reduced the infection risk for patients situated farther away from the corridor within the ward. However, increasing the ventilation rate also resulted in an increase of the infection risk of corridor users and its connected amenities. Installing exhaust grilles close to each patient reduced infection risk within the ward as well as the corridor. Vuorinen et al 55 found that increasing exhaust flow rates and decreasing air mixing was the most effective intervention to reduce infectious particle concentrations.

Two studies analyzing both ventilation rate and airflow patterns provided recommendations. 51, 55 Recommendations included designing ventilation systems so that cross-infection was minimized, with regular ventilation testing and air balancing checks. 51 Additionally, Satheesan et al 54 recommended exhaust placement near patients, ideally above the head of the patient.

Twenty of the 23 modelling studies had low risk of bias for all three domains: definition, assumption, validation (Table 6 ). Two modelling studies had low risk of bias for assumption and validation but had unclear risk of bias for definition as there was a lack of clarity regarding contribution of fresh air in Augenbraun et al, 36 as noted in the differences between Table 2 and . 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 preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint Figure 1 , and regarding the HEPA filter efficiency in Kennedy et al. 45 All eight experimental studies had low risk of bias for all three domains: selection bias, information bias, confounding (Table 7) .

A review of 32 ventilation and coronavirus studies offered several crucial observations. Firstly, increased ventilation, whether through ventilation rates (ACH, m 3 /h, m 3 /min, L/min) or as determined by CO2 levels (ppm), was associated with decreased transmission, transmission probability/risk, infection probability/risk, droplet persistence, and virus concentration, and increased virus removal and efficiency of virus particle removal. Secondly, increased ventilation rate was associated with decreased risk for longer exposure times. Thirdly, the use of ventilation was associated with better outcomes than no ventilation scenarios. Fourthly, airflow patterns were associated with transmission cases. Fifthly, HVAC ventilation feature (supply/exhaust or fans) placement was associated with varied particle distribution. As well, changing ventilation rate or using mixing ventilation is not always the only way to mitigate viruses. Finally, while some studies 

Ventilation is an HVAC feature that incorporates and considers many factors such as ventilation rate, airflow patterns, and air balancing. Additionally, ventilation is affected by outside factors such as room size, airflow rates and volume, filtration usage, exhaust and supply ratios, and number of occupants, to name a few. As such, quantitative recommendations with quantified data can be hard to provide. As Li et al 9 noted in their review, insufficient evidence was found to specify and quantify the minimum ventilation requirements in buildings in relation to the airborne . 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. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint

In practice, ventilation should be used, i.e., something is better than nothing. 30, 40, 45 The ventilation requirements of the HVAC system should consider the occupancy of the space 34,39 and the interplay between ventilation rate, exposure time, and infection risk. 32,34,42 While a variety of settings were addressed, a major portion of the studies (15 of 32) discussed hospitals and/or healthcare facilities. As such, it is important to keep in mind that the portion of studies discussing health care settings (in particular hospitals), with their associated relatively high indoor air quality (IAQ), is not representative of typical filtration and ACH in other identified high risk-oftransmission buildings of concern. Considering diminishing return on improving ACH, practical efforts should be directed at the most high-risk sites (low ACH, crowded, and high risk occupants or activities).

Interestingly, mixing ventilation might not always be the best and other airflow patterns should be considered to lower virus transmission. 46,51,55 These three studies found that alternative airflow patterns were better at negating transmission than mixing ventilation. An important point in most ventilation pattern studies is that they generally require location and characterization of the source, which in practical situations is difficult to ascertain. The decrease in risk available as an outcome is an essential factor to know if innovation and ventilation design are headed in the direction of "smart ventilation" using continuous sensing of occupancy (or even temperature of room occupants) to create control strategies for air supply flow rate and direction. More knowledge of how airflow patterns alone affect risk could lead to systems with real-time feedback control on airflow pattern.

. 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. . 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 preprint this version posted October 11, 2021. . 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 preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 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.

The copyright holder for this preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint Unpublished, not peerreviewed CFD = computational fluid dynamics; HVAC = heating, ventilation, and air conditioning; MERV = minimum efficiency reporting value; UVGI = ultraviolet germicidal irradiation . 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 preprint this version posted October 11, 2021 -"the daily risk of infection for Increased ventilation rate (ACH) 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.

The copyright holder for this preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint healthcare workers was significantly higher than the one for the other patients or the family visitors" (p.2617) -"comparing nurses and other healthcare worker, the result is not significant" (p.2617) -"Other patients in the same room had a statistically significant lower risk of infection compared to nurses . . . but had nonsignificant statistical differences in risk with family visitors" (p,2617) -"For the other patients, mean daily risk of infection could be reduced by about 30% or 58% through increasing the air ventilation from 6 to 9 or 12 ACH" (p.2619) -"For the nurses, healthcare workers, and family visitors, only up to about 2% reduction in mean daily risk could be achieved by increasing the ACH from 6 to 12." (p.2619) . 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 preprint this version posted October 11, 2021 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 preprint this version posted October 11, 2021 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 preprint this version posted October 11, 2021 "We find that for environments with HVAC systems typical of laboratories and offices, it is safe to operate when a room (or section of a room with an isolated airstream) is left vacant for one (high-circulation HVAC with HEPA filtration) to six (low-circulation with no filtration) air exchange times before a new worker enters." (p.453)

Office: "For a typical office room with 2 fresh air changes per hour, this will be approximately 2.5 hr (5 hr) for 3 weeks (26 weeks) of total exposure over 6 months." (p.453)

Lab: "For a typical HEPA filtered lab this would be one air change (for either 3 or 26 weeks of exposure in a 6-month period). For shared lab resources (e.g., electronics rooms, storage cabinets, chemical rooms, etc.) without HEPA filtration, a wait time of at least four air changes will be required (SM Sec. For the mean value E = 970 q/h, increasing the loss rate coefficient from a nominal baseline value of 0.6 to 5h −1 would reduce the probability of infection by a factor greater than two, from 91% to 42%.

For the full range of loss rates plotted in Figure 1 , the infection risks span a factor of eight: from 98% to 13%.

For durations ranging from 0.5 to 2.5 hours, and total loss rates ranging from 0.6 to 12h −1 , the predicted Increased ventilation (loss rate) associated with decreased probability of infection; loss rate due to ventilation increase from 0.3-1.0h -1 percentage infected spanned a broad extent, from 4% to 91%.

At an emission rate of 960q/h probability of infection is reduced from 91% to 42% when loss rate (a factor including deposition, ventilation and inactivation) is increased (Fig 1) Harrichandra Increased ventilation risk (ACH) associated with decreased infection risk . 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 preprint this version posted October 11, 2021 Increased ventilation rate (L min -1 ) associated with lower log reduction and removal efficiencies of viable virus in combination with UV . 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 preprint this version posted October 11, 2021 Hospital room (exposed subject-medical staff): 39 min is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 11, 2021 ventilation rate (ACH) and ventilation location vs risk of particle encounters/ efficiency of particle removal Elevator 30 ACH: infection risk is extremely low in most of the space 2 ACH: little risk to the people who are not standing near the emitter but two orders of magnitude higher risks for some local hot spots Increased ventilation rate (ACH) and increased ventilation settings "(e.g., adding more sites of ventilation)" (p.7) associated with increased efficiency of particle removal Increased ventilation rate associated with less infection index to a particular subject in the room Increased ventilation associated with increased turbulent transport and enhanced dispersion of infectious agent throughout the room . 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 preprint this version posted October 11, 2021 "it is necessary to assess the seating arrangement and operation and location of fans (including ceiling fans) or air conditioners with wind direction and velocity. It is also necessary to ventilation frequently for management of indoor air or to apply a ventilation system or forced ventilation method if natural ventilation is not possible. Furthermore, the distance between tables at an indoor restaurant or cafeteria should be greater than 1-2 m, or installation of a wind partition should be considered based on airflow." (p. 6) Shao (Jan 2021) 26 USA (see also Table 3) Modelling; Classroom, supermarket SARS-CoV-2 Ventilation location vs particle dispersion and risk of infection Classroom:

Ventilation in back corner, far away from the emitter: ventilation spreads particles to the back half of the classroom, student sitting in a hot spot near the vent could inhale several times more particles than a student near the front, increasing their infection risk Ventilation on the same side, near the emitter: spread of particles mostly confined to the front of the classroom before the students. Infection risk significantly reduced compared to ventilation in the back Ventilation and exhaust located near the infectious particle emitter associated with decreased spread of particles which decreases risk of infection

"our results suggest that optimizing ventilation settings (e.g., adding more sites of ventilation) even under the current ventilation capacity can significantly improve the efficiency of particle removal." (p.7)

. 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) 1 weakly positive air sample for SARS-CoV-2 out of 5 was obtained from the corridor close to the patient's isolation rooms (a total of 46 air samples were taken)

Airflow leakage from the isolation rooms to the corridor associated with one weakly positive SARS-CoV-2 air sample AC or A/C = Air-conditioning; HVAC = Heating, ventilation, and air conditioning; ICU = Intensive care unit; SARS = severe acute respiratory syndrome . 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 preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint Air supplied from the room boundary and exhausted in the middle of the room associated with greater efficiency of isolating polluted air.

. 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. Exposure Risk -patients in beds located at 1.625 m away from the corridor: E > 0.05 -patients located at 5.875 m away from the corridor: E < 0.025 Increased ventilation rate (ACH) associated with significant reduction in infection risk for patients in the ward located farther away from the corridor.

Increased ventilation rate (ACH) associated with increase in infection risk of corridor users and its connected amenities.

Installation of exhaust grilles in close proximity to each patient associated with significantly reduced individual patient exposure in the ward.

Installation of exhaust grilles in close proximity to each patient associated with considerably reduced risk of infection transmission to corridor users and its connected amenities.

"it is recommended to provide exhaust grilles in close proximity to a patient, preferably above each patient's bed." (p.8)

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The copyright holder for this preprint this version posted October 11, 2021 Mixing ventilation device on + 0.18 or 1.8m 3 s -1 ceiling exhaust: effective dilution which decreased the normalized concentration to 10 -4 -10 -3 further away from the cough Mixing ventilation device off + 1.8 m 3 s -1 ceiling exhaust: most effective reduction of particle concentration Increased exhaust ventilation rate and less air mixing associated with greater dilution of airborne particles. ACH = air changes per hour; EA = Exhaust airflow; SARS = severe acute respiratory syndrome . 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)

The copyright holder for this preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint 27 Low Low Low Lim (Jan 2010) 52 Low Low Low Chen (Oct 2011) 53 Low Low Low Yu (2017) 28 Low Low Low You (Sept 2019) 46 Low Low Low Adhikari (Sept 2019) 29 Low Low Low Satheesan (Feb 2020) 54 Low Low Low Zemouri (Jul 2020) 35 Low Low Low Riediker (Jul 2020) 31 Low Low Low Dai (Aug 2020) 34 Low Low Low Anghel (Sept 2020) 48 Low Low Low Augenbraun (Sept 2020) 36 Unclear Low Low Miller (Sept 2020) 41 Low Low Low Harrichandra (Oct 2020) 42 Low Low Low Vuorinen (Oct 2020) 55 Low Low Low Zhang (Oct 2020) 37 Low Low Low Sun (Nov 2020) 39 Low Low Low Melikov (Nov 2020) 44 Low Low Low Buonanno (Dec 2020) 32 Low Low Low Shao (Jan 2021) 26 Low Low Low Borro (Feb 2021) 33 Low Low Low Kennedy (Mar 2021) 45 Unclear Low Low 40 Low Low Low Somsen (May 2020) 30 Low Low Low Lu (July, Nov 2020) [24] [25] Low Low Low Miller (Oct 2020) 49 Low Low Low Kwon (Nov 2020) 47 Low Low Low Ding (Jan 2021) 50 Low Low Low * Confounding assessed for our comparison of interest.

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The copyright holder for this preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 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 ventilation and coronavirus 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)

The copyright holder for this preprint this version posted October 11, 2021. ; https://doi.org/10.1101/2021.10.08.21264765 doi: medRxiv preprint

American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE)

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