3

Effectiveness of Non-Vaccine Control Measures

During epidemics and pandemics of respiratory viruses, non-vaccine public health control interventions have been implemented in diverse settings across the world to reduce viral transmission and curb the spread of disease. This chapter provides a high-level overview of the available evidence regarding the effectiveness of such interventions during the coronavirus disease 2019 (COVID-19) pandemic. The aim is to analyze lessons that can be applied toward strengthening influenza preparedness—including individual-level actions, building and environmental controls, and government and public health controls—rather than offering an exhaustive or comprehensive review. The overview highlights relevant findings and scientific evidence gleaned from research conducted on various measures primarily during COVID-19 and on related types of respiratory virus events. Based on expert guidance, this overview draws from a range of different research domains and methodologies but predominantly relies on studies that show reduced basic reproduction number (R₀), such as randomized controlled trials (RCTs) and systematic reviews, and on laboratory and physical modeling studies that quantify the extent to which specific interventions (e.g., masks, portable air filtration units) can prevent the spread of a virus. It also includes evidence from natural experiments that produce data on interventions being used at varying rates in different settings.

The research strategy for this analysis accounts for the wide variability in the optimal way to assess the evidence available for each type of non-vaccine control measure that was evaluated. For medical and public health research, evidence generated from RCTs is typically considered the gold standard (Greenhalgh, 2020; Pearson, 2021). However, some relevant pub-

lic health interventions cannot be tested using RCTs because it is unfeasible (e.g., national border closure) or unethical in contravening the core tenets of public health, warranting ecological or observational studies to evaluate their effectiveness. Certain fields, such as aerospace engineering, maintain a very low tolerance for error yet rely on laboratory and modeling tests and systematic experimentation. The COVID-19 pandemic has not allowed for many RCTs or trials of any kind, so many policies have had to be based on modeling predictions. For instance, many of the most informative analyses of the impact of face masks, ventilation, and airflow on aerosolized virus transmission come from fundamental principles and research in science and engineering. This pandemic has also illustrated the importance of multidisciplinary study and incorporating lessons and understanding from other fields that do not conduct RCTs, such as industrial hygiene and aerosol science, previously not often included in pandemic planning and response. This is an opportunity to open the framework of public health policy to the broader set of tools of the scientific method from both the medical and biological perspective and rigorous and error-averse classes of physical sciences. This chapter defines evidence for effectiveness as a measure’s ability to reduce virus transmission and primarily explores effectiveness in this regard. Chapter 4 will explore the various contextual factors that can affect the population’s implementation and optimization of such measures and thereby play into whether particular measures should be recommended for certain settings.

ECONOMIC IMPLICATIONS OF NON-VACCINE CONTROL MEASURES

The economic implications of implementing non-vaccine measures alone to control the COVID-19 pandemic remain largely unquantified. However, a study examined the potential health and economic impacts of mass vaccination in the United Kingdom and showed that with lower-efficacy vaccines, non-vaccine measures will be required long term (over 10 years) (Sandmann et al., 2021). In the best-case scenario, mass immunization with a 95 percent efficacious vaccine, coupled with physical distancing measures, was predicted to yield incremental net monetary values of £12.0–£334.7 billion. Furthermore, community transmission would be minimized without the need for future increases in physical distancing measures. An economic evaluation indicates that lockdowns and physical distancing reduce economic losses, contrary to a prevailing view that such public health pandemic-control measures necessarily undermine economic protection and recovery efforts (MacIntyre, 2021). A modeling study in Australia found the economic costs of an early, mandated lockdown in March 2020 to be multiple times less compared to no interventions (Kom

pas et al., 2021). An analysis of Portuguese data found that the costs of scaling up COVID-19 testing would be lower than hospitalization costs in most scenarios (Sousa-Pinto et al., 2020), while another study determined that for every euro spent on testing, seven euros would be returned in terms of saved health care expenditures (González López-Valcárcel et al., 2021). A Ugandan cost–benefit analysis found the per capita compounded cost of providing face masks to be around USD 1.34 per Ugandan versus USD 4.00 for medical treatment per individual who becomes infected, possibly due to not wearing a mask (Nannyoga et al., 2020). While the evidence is limited, non-vaccine measures, particularly masks, likewise have been suggested to be cost-effective for seasonal and pandemic influenza (Howard et al., 2021; Mukerji et al., 2015; Tracht et al., 2012).

EVIDENCE FOR INDIVIDUAL-LEVEL ACTIONS

A number of non-vaccine interventions rely on individual actions that have played a pivotal role in reducing the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Such actions have included face masks, appropriate hand hygiene, and different physical distancing measures. However, a discussion of these measures without supportive effective risk communication, health education, and community engagement is likely to achieve suboptimal impacts regardless of the intervention proposed. Chapter 4 discusses more on these important contextual factors.

Face Masks

Laboratory studies, RCTs, and observational studies have demonstrated the effectiveness of face coverings in reducing the transmission of SARS-CoV-2; this impact is believed to apply to influenza as well (Cowling et al., 2009). However, in a real-world setting, the effectiveness of different types of masks varies widely and is largely dependent on the wearer ensuring an appropriate fit. During COVID-19, the World Health Organization (WHO) issued guidance and standards for face masks to achieve appropriate filtration, breathability, and fit (WHO, 2020a) and recommended that masks should have three layers of fabric, including an inner layer of absorbent material, a middle layer of nonwoven nonabsorbent material, and an outer layer of nonabsorbent material (WHO, 2020a).

The National Academies conducted a Rapid Expert Consultation on the Effectiveness of Fabric Masks for the COVID-19 Pandemic in April 2020; despite limited experimental studies available at the time, it highlighted important considerations. Studies showed that a variety of masks reduced emissions of droplets generated by speech (NASEM, 2021), cloth and surgical masks reduced exhaled particle emissions (by one-fifth and

one-half, respectively) (van der Sande et al., 2008), and homemade masks and surgical masks reduced the number of large-sized microorganisms expelled while coughing (Davies et al., 2013). Authors of the rapid expert consultation acknowledge the limited real-world evidence for different types of homemade fabric masks, but laboratory evidence suggests they can reduce transmission of larger respiratory droplets, although the level of protection will be influenced by the user’s behavior.

Laboratory and Modeling Studies

A laboratory study of 32 materials used in cloth masks (i.e., cotton, wool, synthetic, synthetic blends, synthetic/cotton blends) with nanometer-sized aerosol particles, found that the five best-performing materials, in terms of filtration efficiency and differential pressure, were three woven 100-percent cotton samples with high-to-moderate yarn counts and two woven synthetics with moderate yarn counts (Zangmeister et al., 2020). In another laboratory study of 44 homemade face-mask materials, decent filtration efficiencies were achieved over a large range of particle sizes by stacking an adequate number of fabric layers and ensuring good fit to reduce leak flows (Drewnick et al., 2021). Similarly, a laboratory evaluation of 11 face coverings determined that a well-fitting three-layer mask with an outer layer of flexible, tightly woven fabric and an inner fabric layer designed to filter particles could provide a minimum of 70 percent filtration efficiency against the most penetrating particles (~0.3 μm) (Pan et al., 2021). Likewise, a study of different fabrics for source control of a human-generated sneeze found that a three-layer mask could outperform a surgical mask and that machine washing did not significantly affect performance; hydrophilicity/wettability of the materials should also be considered (Bhattacharjee et al., 2021). Moderate evidence from laboratory studies with patients suggests that surgical masks also reduce aerosol shedding of seasonal influenza virus (Leung et al., 2020; Milton et al., 2013).

A spate of recent studies from the perspective of fluid dynamics has also demonstrated the efficacy of masks. Computational fluid dynamics simulations have shown that masks can limit the spread of respiratory emissions while also offering some protection to the wearer (Dbouk and Drikakis, 2020; Khosronejad et al., 2020). Visualization using laser sheets has shown that well-fitted masks with multiple layers and those with extra space in front of the nose and mouth were more effective than loose masks in limiting droplet dispersal (Verma et al., 2020).

Together, these studies show that a mask’s fit is critical to its performance. Good design (choice of material, configuration and number of layers, antimicrobial activity) can greatly improve performance (Brooks et al., 2021; Pan et al., 2021; Rothamer et al., 2021). The best-performing masks

feature multiple layers of material, excellent filtration capabilities of at least one of the layers, and a tight fit with no leaks. Other factors to consider include breathability, durability, cost, and reuse.

Randomized Controlled Trials and Observational Studies

A meta-analysis of 10 RCTs on community-based use of masks in reducing influenza transmission found no evidence of substantial effect, although it did recommend that masks be worn by symptomatic and uninfected persons during severe epidemics and pandemics (WHO, 2019). However, a systematic review of 172 observational studies across 16 countries and 6 continents that looked specifically at the risk of infection with beta-coronaviruses (e.g., SARS, SARS-CoV-2, Middle Eastern respiratory syndrome-related coronavirus [MERS-CoV]) found that physical distancing of greater than or equal to 1 meter was associated with a substantial reduction in infection, with additional benefit conferred by face masks and eye protection (Chu et al., 2020). Moreover, according to a rapid systematic review of 19 RCTs, community-based mask use appeared effective in reducing the risk of respiratory virus infection even without appropriate hand hygiene, although the combination of measures would likely be more effective (MacIntyre and Chughtai, 2020). Although a Danish RCT conducted early in the COVID-19 pandemic found no statistically significant difference in infection rates between users randomly assigned to a recommendation of face masks and controls (Bundgaard et al., 2020), the results were met with debate. It was argued that the study did not account for the role of mask use in reducing transmission to others (Abbasi, 2020) and only examined the effect of recommending mask use, rather than actually wearing masks (Laine et al., 2021).

Mask Mandates

The COVID-19 pandemic has featured increasing calls to implement national- or local-level mask mandates. Modeling has suggested that requiring mask use by the entire public, not just symptomatic individuals, could achieve a median effective R₀ of below 1, even with mask effectiveness of just 50 percent (Stutt et al., 2020). These findings are supported by a mathematical modeling study in Victoria, Australia, that illustrated how rates of mask use greater than 50 percent can substantially improve epidemic control, even without other measures (e.g., lockdowns) and with masks offering low-to-moderate protection (Costantino et al., 2020). In the United States, implementation of mask mandates has been linked to decreases in daily COVID-19 case and death growth rates within 20 days (Guy et al., 2021b). Thirteen U.S. states that reopened with mask mandates in spring

2020 prevented an estimated 50,000 excess deaths within 6 weeks; excess cases and excess deaths could have been reduced from 576,371 to 63,062 (about 90 percent) and from 22,851 to 4,858 (about 80 percent), respectively, within 6 weeks had other states implemented mask mandates before reopening (Kaufman et al., 2020). An analysis of mask use in the United States, the United Kingdom, and Australia found mandates to be predictors of mask wearing (MacIntyre et al., 2021), and a study of U.S. states with the lowest mask adherence were found to have the highest COVID-19 rates (Fischer et al., 2021), further suggesting that mask mandates may be effective in reducing virus transmission.

Mask mandates have also been found to reduce transmission amidst restaurant reopening during COVID-19: an increased risk of cases was attenuated by up to about 90 percent and deaths up to 80 percent in U.S. states that implemented statewide mask mandates prior to reopening restaurants for indoor dining (Guy et al., 2021a). An analysis in Hong Kong during a mask mandate found that most COVID-19 transmission occurred in mask-off settings, such as households and restaurants, supporting the effectiveness of masks (Martín-Sánchez et al., 2021).

Face Shields

Face shields are infection control measures widely used during the COVID-19 pandemic, often in lieu of face masks. Although face shields are designed to be worn over a mask in health care settings, they are not meant to serve as sole respiratory protection. However, they are often used under the mistaken presumption that SARS-CoV-2 and other respiratory viruses spread through ballistic strikes with large droplets rather than inhalation of aerosols. Face shields can protect the eyes from ballistic strikes, but they will not reduce inhalation exposure. In addition, evidence suggests they are not effective. These findings are valid for aerosols of any type, so they are expected to apply to influenza viruses carried in small aerosols. In laboratory studies, a face shield blocked the emission of just 2–4 percent of total cough aerosols, much less than other types of face coverings (Li, L. et al., 2020a; Lindsley et al., 2020). A study with coughing patient and breathing worker simulators found that although face shields can be useful adjuncts, they cannot substitute for respiratory protection (e.g., face masks) against influenza-laden aerosols (Lindsley et al., 2014), which is the general guidance for health care workers (Roberge, 2016).

Hand Hygiene

Hand hygiene is another frequently used intervention against respiratory viruses, despite relatively little evidence of its effectiveness. A

systematic review of RCTs found that hand hygiene did not appear to have a substantial effect on the transmission of laboratory-confirmed influenza—based on a moderate quality of evidence—although mechanistic studies have shown that it can deactivate or remove influenza virus from hands (WHO, 2019). An evaluation of Taiwan’s early response to the COVID-19 pandemic suggests that universal hygiene—including handwashing—and mass masking contributed to a 50 percent decline in infectious respiratory illnesses, including COVID-19, influenza, and influenza-like illnesses (ILIs) (Hsieh et al., 2020). The results of a randomized trial in university residence halls during influenza season suggest that the combination of hand hygiene and face masks significantly reduced the incidence of ILI in shared living spaces (Aiello et al., 2010). In Hong Kong, masks plus hand hygiene were protective if used early, but hand hygiene alone was not (Cowling et al., 2009). During the 2009 influenza A (H1N1) outbreak in Bangkok, Thailand, a study of influenza virus contamination in homes with an infected child found that increased handwashing was not associated with protection, despite an earlier study showing that the hands of children with influenza were contaminated with the virus (Simmerman et al., 2010). However, like masks, it is important to track the details of hand hygiene, as these impact its effectiveness. More research is needed to assess the efficacy of interventions such as handwashing, coupled with ventilation of common facilities, such as restrooms, where handwashing takes place.

Physical Distancing Measures

Physical distancing reduces the risk of respiratory virus transmission by positioning people beyond the range of large, ballistic respiratory droplets and away from high concentrations of aerosol particles in a freshly emitted respiratory plume. The optimal distance remains a matter of debate, although the emerging scientific view is that no universal safe distance is applicable to specific pathogens, especially when considering physical activity, occupancy level, and characteristics of the built environment. During the COVID-19 pandemic, guidance from WHO and many national governments recommended physical distancing of 1.5–2 meters to reduce airborne transmission. However, a narrative review has proposed that recommendations of 1–2 meters are premised on outdated assumptions about respiratory droplet size and may neglect factors that affect the distribution of viral particles, such as airflow, ventilation, and the means and frequency of expulsion (Jones et al., 2020). A range of 1–2 meters is also impractical, as it is not specific enough. Respiratory droplets of up to 60 μm in size have been shown to travel a horizontal distance of more than 2 meters, suggesting that SARS-CoV-2 could

achieve such distances during coughing or shouting (Bahl et al., 2020). Aerosols, of course, can travel much farther, carried by air currents. Other research has supported the hypothesis that SARS-CoV-2 can be transmitted beyond a distance of 2 meters, due to its higher aerosol and surface stability (Setti et al., 2020). A systematic review of 172 observational studies from 16 countries suggests that physical distancing greater than 1 meter was associated with a lower beta-coronavirus transmission than distancing less than 1 meter; protection increased up to 3 meters, which was the longest distance for which data were available (Chu et al., 2020). However, these evaluations did not account for local airflow patterns; distancing without doing so cannot evaluate the role of distancing as a control measure beyond 1 meter.

A Rapid Expert Consultation on Social Distancing During the COVID-19 Pandemic conducted by the National Academies in March 2020 also highlighted the effectiveness of physical distancing (NASEM, 2021). Much of the evidence was based on previous influenza experience and found that it is not always well defined but is generally most effective when implemented early. A study in Wuhan noted that the reproductive number dropped from 3.86 to 1.26 following the introduction of several physical distancing measures (Wang et al., 2020). However, implementation matters. Additional modeling exercises from Imperial College London suggested that a 3-month period of intervention stressing distancing could reduce deaths by half and health care demand by two-thirds. But if only half measures were put into place (i.e., only elderly people versus the whole population), the epidemic could overwhelm health systems in the United States and lead to more than 1 million deaths (Ferguson et al., 2020).

A natural experiment across 149 countries and regions found that implementing any type of physical distancing intervention was associated with a 13 percent overall reduction in COVID-19 incidence in the pandemic’s early months (Islam et al., 2020). However, an observational study in the United Kingdom suggests that current physical distancing measures in schools are insufficient to combat the spread of rhinovirus, influenza, and potentially SARS-CoV-2 (Poole et al., 2020). Drawing largely from observational and simulation studies, a systematic review of physical distancing measures found that they could be effective during a pandemic in terms of reducing transmission and mitigating overall impact (Fong et al., 2020).

A summary of the evidence of various individual measures explored in this chapter (see Table 3-1) and a list of potential research topics that need additional study in this area (see Box 3-1) are outlined below.

TABLE 3-1 Individual-Level Measures: Evidence Supporting Efficacy/Effectiveness* in Reducing Transmission of Respiratory Viruses

* “Efficacy” refers to data from RCTs; “effectiveness” refers to data from experimental or observational epidemiologic studies.

EVIDENCE FOR BUILDING AND ENVIRONMENTAL CONTROLS

Buildings have been associated with the spread of infectious diseases, such as of influenza and COVID-19, which has highlighted the role of building and environmental controls in reducing transmission during epidemics and pandemics. Measures have included plexiglass barriers, ventilation and filtration systems, ultraviolet (UV) inactivation, ionization, and surface cleaning, but the availability and quality of evidence for their effectiveness varies widely.

Barriers

The effectiveness of barriers, such as clear plastic, as infection control measures has not yet been investigated directly, but a 2013 study of physical partitions between beds in a hospital ward found that airborne pathogen infection risk was not reduced; it merely shifted to different rooms (Gilkeson et al., 2013). Desk shields in schools have been found to be associated with increases in the risks of COVID-19-related symptoms (Lessler et al., 2021). In some situations, barriers, whether plexiglass or otherwise, could be helpful in mitigating transmission, such as clinical or other visits where there are just two people in a room. However, for this to be effective, proper ventilation is correspondingly required to remove aerosols that are diverted by the barriers. A study measuring barrier efficiency for worker protection found that a barrier that blocked an initial cough from a simulator was effective at reducing particle counts, but the height of the barrier was more significant than the width in determining efficiency (Bartels et al., 2021). However, barriers can create “hot spots” in a room and increase exposure to those who may be nearby, so it is important for airflow in the room and ventilation to be considered as well.

Ventilation and Filtration

Science and engineering research has linked poor ventilation with increased risk of transmission of respiratory pathogens. Similarly, observational and modeling studies of tuberculosis (TB) over previous decades have also shown the influence that ventilation can have on outbreaks. For example, modifications to improve cross-ventilation and open air in hospitals in Peru resulted in a median 72 percent reduction in calculated TB transmission risk (Escombe et al., 2019). A study in Taiwan measured the effect of improving ventilation rate on a TB outbreak in less ventilated university buildings and found that levels with carbon dioxide less than 1,000 ppm was associated with a 97 percent decrease in TB incidence among contacts (Du et al., 2020).

Most outbreaks of COVID-19 involving at least three people have been associated with time spent indoors, highlighting the importance of good ventilation (Allen and Ibrahim, 2021). SARS-CoV-2 can be spread through “far-field” airborne transmission within the same room but over distances greater than 2 meters (Allen and Ibrahim, 2021). In March 2020, poor ventilation was implicated in the superspreading event for the Skagit Valley chorale in the U.S. state of Washington, which was likely exacerbated by generating large volumes of respiratory aerosolized virus during singing (Miller et al., 2021). Similarly, airborne spread of SARS-CoV-2 was also shown to be likely in a church outbreak involving singing in Australia, despite physical distancing; cases occurred in people who were up to 15 meters away from the index case with no close physical contact (Katelaris et al., 2021). As all secondary cases were seated in a certain section behind the singer, this study illustrated the importance of airflow direction.

Inadequate ventilation has also been regarded as contributing to outbreaks within nursing homes (de Man et al., 2020) and restaurants (Li, Y. et al., 2020; Lu and Yang, 2020). An analysis of an incident in which three individuals caught SARS-CoV-2 in a restaurant in South Korea found that with direct airflow from a person who is infected, droplet transmission can occur over distances greater than 2 meters (Kwon et al., 2020). An investigation of 169 schools in the U.S. state of Georgia found that improved ventilation by opening windows and doors or using fans was associated with a 35 percent lower incidence of COVID-19 among students and staff (Gettings, 2021).

In health care, office buildings, apartments, and other high-occupancy settings, routes of airflow and ventilation should be considered in strategies to mitigate risk of airborne transmission of respiratory viruses. In a randomized human-challenge influenza transmission study, the secondary attack rate was significantly lower than expected based on the preceding proof-of-concept study, with mechanical building ventilation in the follow--

on study being the main variable (Nguyen-Van-Tam et al., 2020). A study examining building ventilation and laboratory-confirmed acute respiratory infections was conducted in two U.S. university residence halls, one with high ventilation—via a dedicated outdoor air system supplying 100 percent of outside air to each room—and one with low ventilation relying on infiltration (Zhu et al., 2020). Residents in the former were found to have much lower incidence of acute respiratory infection during the study period (1 case versus 47 cases). Opening both windows and doors in the low-ventilation building increased ventilation rates roughly to the level of the high-ventilation building.

Air cleaners, when properly installed to account for space and airflow, represent a simple, cost-effective intervention for reducing aerosol transmission. In a COVID-19 ward at a hospital in Melbourne, Australia, a study of the transmission of aerosols from a patient room into hallways and a nurses’ station found that aerosols traveled rapidly. However, air cleaners (i.e., portable high-efficiency particulate air [HEPA] filters) increased the clearance of aerosols from the air and reduced their spread: two small air cleaners can clear 99 percent of aerosols from a patient room within about 5 minutes (Buising et al., 2021). Similarly, an analysis of the use of four HEPA-filter air purifiers (air exchange rate 5.5 h^–1) in a high-school classroom in Germany found that they reduced the aerosol number concentration by greater than 90 percent within 30 minutes in a room with doors and windows closed, thus substantially reducing the risk of SARS-CoV-2 transmission (Curtius et al., 2021). In a study of schools in the U.S. state of Georgia, HEPA filtration in addition to ventilation improvements were associated with a lower incidence of COVID-19 compared to ventilation improvements alone (Gettings, 2021). Filtration and ventilation with outdoor air are complementary tools. Optimizing their application depends on the specifications of the heating, ventilation, and air conditioning (HVAC) system, outdoor air quality, and other factors. For example, when areas are impacted by wildfire smoke, people should not rely on ventilation with outdoor air. On the other hand, increasing the quality of filters in an HVAC system can lead to reduced ventilation rates or place strain on the equipment. HEPA filters should be maintained and replaced in accordance with the system’s guidance to ensure optimal system function and reduce strain (Zhao et al., 2020).

Ultraviolet Inactivation and Ionization

UV germicidal air disinfection is an engineering method that can be used to control the transmission of airborne pathogens in high-risk environments (Walker and Ko, 2007). A laboratory study demonstrated that 254-nm ultraviolet germicidal irradiation (UVGI) may be an effective measure

to prevent the transmission of respiratory viral diseases (Walker and Ko, 2007). Furthermore, research has shown SARS-CoV-2 specifically to be inactivated by UV (Heilingloh et al., 2020). The design of a UVGI system is critical in optimizing its performance. A simulation study reported that both ceiling height and mounting height of UVGI fixtures in hospital rooms can contribute to variation in upper-zone fluence rate of up to 22 percent (Hou et al., 2021). The study also demonstrated that interreflections within a room should be considered when designing UVGI fixture placement in the upper part of a room, to avoid creating “hot spots” where a room’s occupant could be in danger of being overexposed to UV in the lower part. Effective application of UVGI also requires adequate analysis of airflow and flow dynamics of the room to avoid creating areas with high pathogen concentrations.

Claims for the efficacy of ionization have not been independently verified (Zeng et al., 2021). Furthermore, ionization may cause harmful byproducts and has not been recommended by the U.S. Centers for Disease Control and Prevention (CDC) or the American Society of Heating, Refrigerating, and Air-Conditioning Engineers.

Surface Cleaning

Evidence is weak to nonexistent that measures such as surface cleaning are effective in reducing the transmission of SARS-CoV-2. According to U.S. CDC, the risk of fomite-mediated transmission considered relatively low compared to direct contact, droplets, or airborne transmission (CDC, 2021b). Quantitative microbial risk assessment studies on the relative risk of SARS-CoV-2 fomite transmission suggest that the risk from coming into contact with a contaminated surface is just 1 in 10,000 (CDC, 2021b). A study conducted in intensive care units (ICUs) treating COVID-19 patients found that basic cleaning with standard disinfection measures was sufficient to eliminate SARS-CoV-2 RNA from surfaces (Hofmaenner et al., 2021). However, during biweekly virus monitoring in four U.S. primary school classrooms, greater than 20 percent of the school desks sampled had detectable DNA and RNA from respiratory viruses and norovirus. Based on the occurrence patterns, if more than five desks were occupied per day, the room occupants had a greater than 60 percent chance of encountering any virus, most commonly rhinoviruses and adenoviruses (Zulli et al., 2021). Additionally, the relation between surface type and property matter remain poorly understood (Otter et al., 2016).

A summary of the evidence of various building and environmental control measures explored in this chapter (see Table 3-2) and a list of potential research topics that need additional study in this area (see Box 3-2) are outlined below.

TABLE 3-2 Building and Environmental Control Measures: Evidence Supporting Efficacy/Effectiveness* in Reducing Transmission of Respiratory Viruses

* “Efficacy” refers to data from RCTs; “effectiveness” refers to data from experimental or observational epidemiologic studies.

EVIDENCE FOR GOVERNMENT AND PUBLIC HEALTH CONTROLS

Governments and public health agencies have instituted a number of restrictions and mandates to control the spread of COVID-19. Although these controls have demonstrated effectiveness in reducing virus transmission overall, they have other potential implications that could have bearings on future influenza preparedness efforts. These measures have included travel restrictions, lockdowns, and mandates for curfew, school and business closures, testing, and quarantine. However, instituting and enforcing these measures without supportive and effective risk communication, health education, and community engagement in advance is bound to achieve suboptimal impacts. Adding to the complexity is the ongoing learning curve regarding household transmission for initial COVID-19 strains and emerging variants. Regardless of the type of measure, it is important for researchers and policy makers to understand the mode of transmission to be able to best inform when certain measures are implemented and in what settings. When the pandemic began in early 2020, a study of the wild-type SARS-CoV-2 found that patients had the highest viral load in throat swabs at the time of symptom onset, with an estimated 44 percent presymptomatic transmission (He et al., 2020). This helped fuel policies such as temperature checks and ensuring people stayed home when sick. However, in a study in summer 2021 examining the transmission dynamics of the Delta variant in an outbreak in southern China, researchers found that those infected with the variant had a more rapid symptom onset (incubation period of 5.8 days) and higher viral load and that nearly 74 percent of the transmissions occurred before symptom onset (Kang et al., 2021). Understanding how the virus spreads from person to person should guide how public health measures are implemented.

Currently, sufficient evidence is lacking for most effective interventions within a household, especially in poorer, crowded environments where

people are more densely living. However, screening programs or free testing may not be successful if there are no guarantees of payment or a safety net if a person tests positive and needs to quarantine for a longer period. Evidence is also lacking on whether the entire household needs to quarantine, and for how long, if one person tests positive. Careful study on this would be helpful in understanding the epidemiology and informing policy decisions and guidance. More on the critical importance of these various contextual factors is also discussed in Chapter 4.

Travel Restrictions

Many countries have enacted non-vaccine control measures related to international travel in response to the COVID-19 pandemic, such as inbound/outbound traveler screening, quarantines, and other travel restrictions. Some countries have even imposed border closures or other stringent border controls, such as banning entry by all non-nationals and, in the case of Australia, even Australian nationals returning to the country from India in May 2021. Such policies can be contentious because they run contrary to International Health Regulations (IHR) advice that nations should avoid closing their borders to avert restrictions on international travel and trade. Because of this, WHO has not recommended border closures during the COVID-19 pandemic (WHO, 2020b). However, some advocates have called for modifying the IHR to be more flexible to allow for limiting international travel and trade at early points in epidemics, where this action could positively influence the outbreak direction (von Tigerstrom and Wilson, 2020). This would ideally be coupled with a fund to support countries that are economically affected by the restrictions and strategies to effectively reopen when appropriate. As various countries have enacted different levels of travel restrictions, it has been clear that some interventions are more successful in certain locations depending on geography, culture, or population. This section outlines the evidence for different types of restrictions on the case count or levels of community transmission, but the contextual factors for where and when these interventions are most successful can be difficult to distinguish, and more understanding is needed.

Evidence for the effectiveness of travel-related restrictions to halt the spread of viral transmission is mixed (Burns et al., 2021; Kang et al., 2020), and it is ecological or observational by necessity. However, evidence around the emergence of variants of SARS-CoV-2 in early 2021 appears to provide some justification for border restrictions from an epidemiological stance (Mallapaty, 2020; Pham et al., 2021). Evidence for reducing virus transmission stands apart from considerations about whether such policies are sustainable and equitable, able to isolate the disease but not the people in the countries with such restrictions, taking into account many factors, such

as ensuring that such measures do not hamper the medical/supply chain and international medical staff supporting countries in the epidemic and pandemic response.

Geography and timing are critical considerations in travel-restriction measures. Countries such as Australia and New Zealand implemented travel bans combined with hotel quarantine of all incoming travelers early in 2020—before community transmission was established—and were able to largely avert the deleterious impacts of COVID-19 experienced by countries that did not do so quickly (Huang et al., 2021). This suggests that island nations may have more success with travel measures than countries with porous national borders, as evidenced by the success of New Zealand’s strict border control strategies. As of January 2021, the country had just 2,262 probable and confirmed cases—and 25 deaths—in its population of 5.1 million (Baker et al., 2020). Furthermore, travel bans are only effective before substantial community transmission is established (Cumming, 2021). Modeling studies suggest that Australia’s first travel ban for China reduced imported cases by 79 percent, delayed widespread transmission by about 1 month (Adekunle et al., 2020), and averted a larger-scale epidemic by restricting incoming passengers from China when COVID-19 was largely localized in Wuhan (Costantino et al., 2020).

A rapid systematic review of 29 studies reported a high degree of consensus that travel-restriction measures contributed substantially to changes in the dynamics of the COVID-19 pandemic, particularly when implemented during the early phases (Grépin et al., 2021). For instance, immediate restrictions in Wuhan were associated with a 70–80 percent reduction in cases exported to other countries and reductions in transmission within mainland China. Restrictions on flights in and out of China also likely contributed to further reductions in the volume of exported cases. A caveat is that most studies only evaluated international travel measures and did not account for domestic travel measures, potentially biasing their estimates of effectiveness. Moreover, a systematic review of 15 studies found no evidence suggesting that screening inbound travelers would substantially reduce the spread of pandemic influenza; no studies reviewed had evaluated the effect of screening outbound travelers (Ryu et al., 2020).

A rapid review of 40 experimental, observational, and modeling studies on travel-related control measures in response to COVID-19, SARS, and MERS-CoV found a low certainty of evidence for their effectiveness based on cases detected or averted. However, the authors posited that travel restrictions could have a positive impact on certain outcomes. For instance, although evidence for separate measures, such as symptom screening and quarantine, was not sufficient to draw conclusions about their effectiveness when implemented alone, combinations of measures (e.g., screening, observation, testing) would likely improve effectiveness. Evidence from this

study was insufficient to draw conclusive findings about the effectiveness of a quarantine related to travel as a stand-alone control intervention. However, they noted that effects probably depend on factors such as epidemic phase, countries’ interconnectedness, and local-level measures to contain transmission (Burns et al., 2020).

Public health measures against COVID-19, particularly border closures, may also reduce transmission of other types of respiratory viruses. In Australia, stringent restrictions on movement within and into the country may have temporarily eliminated influenza in March 2020, when winter approached for the southern hemisphere and Australia was expected to experience high, concurrent levels of SARS-CoV-2, influenza, and other seasonal respiratory viruses. Influenza notifications, hospitalizations, and deaths were substantially lower compared to influenza seasons in previous years, based on national ILI sentinel surveillance and national sentinel hospitalization data (Sullivan et al., 2020). Another study found that Western Australia had huge reductions in the number of cases of respiratory syncytial virus (98.0 percent) and influenza (99.4 percent) among children through winter 2020, despite schools reopening (Yeoh et al., 2020).

Lockdowns and Curfew

Some evidence suggests that government-imposed lockdown and curfew measures may reduce the transmission of SARS-CoV-2 and potentially influenza (Sullivan et al., 2020) but with wide-ranging implications. An evaluation of French Guiana’s COVID-19 control strategy found that a combination of interventions, including curfews and targeted lockdowns, was associated with a decline in R₀ from 1.7 to 1.1 (Andronico et al., 2021). A systematic review evaluated the effectiveness of lockdown with or without mass testing in controlling COVID-19 (Johanna et al., 2020). Ten of the studies suggested that lockdowns reduced incidence, onward transmission, and mortality rate, with limited evidence that combining lockdown and mass screening was more effective in reducing incidence and mortality rates than lockdown alone. Insufficient evidence was available to evaluate the effectiveness of mass screening, however.

Stay-at-Home Orders

An evaluation of U.S. physical distancing policies found that statewide stay-at-home orders and limits on restaurants and bars were linked to reductions in out-of-home mobility (15.2 percent and 8.5 percent, respectively) early in the pandemic, but the other policies studied—such as nonessential business closures, limited stay-at-home orders, school closure mandates, and bans on large gatherings—were not, perhaps due to the

benefits of voluntary physical distancing (Abouk and Heydari, 2021). Another study looked at the relationship between confirmed COVID-19 cases and U.S. state or local social distancing measures, including (1) large social gathering bans; (2) school closures; (3) entertainment venue, gym, bar, and restaurant dining area closures; and (4) shelter-in-place orders. The analysis suggests that in March and April 2020, without shelter-in-place orders or any of the four interventions, COVID-19 would have had 10-fold or 35-fold greater spread, respectively (Courtemanche et al., 2020). A natural experiment found that as England transitioned from national lockdown to localized interventions and tiered mitigation strategies, survey respondents tended to report fewer social contacts after each measure was introduced, albeit with small and variable magnitudes of change (Jarvis et al., 2021).

Children/School Closures

School closures have demonstrated effectiveness in curbing community outbreaks of influenza (Bin Nafisah et al., 2018; Jackson et al., 2013; Stebbins et al., 2010), and this strategy has been frequently part of national and local COVID-19 pandemic response. However, it is not likely that sustained school closures are as effective in preventing community spread of COVID-19 as they are for influenza, due to important differences in the age profiles of infectivity and susceptibility (Heald-Sargent et al., 2020). Research has demonstrated that children less than 10 years old tend to have lower levels of infectivity than adults and thus are unlikely to be primary drivers of SARS-CoV-2 community transmission (Bullard et al., 2021; Kim et al., 2020).¹ In contrast, young children represent a major source of influenza transmission because they tend to shed the virus for longer than adults, in both the pre- and post-symptomatic periods (Heald-Sargent et al., 2020; Ng et al., 2016). The age profile of students within a school is another consideration relevant to decisions about school and university closures. For example, emerging evidence suggests that young adults of university age have higher levels of infectivity and susceptibility to COVID-19 than children under age 18. However, with variants, such as Delta, influencing these factors, this may not continue to be accurate. A preprint from the United Kingdom demonstrated that younger groups were driving much of the latest surge in cases, with fivefold higher rates of swab positivity among younger children (5–12 years) and young adults (18–24 years) (Riley et al., 2021). Generally, older adolescents and young adults are thought to represent

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¹ As mentioned in Chapter 1, this report reflects the state of the science when it was written in summer 2021. As new strains emerge and data on children’s infectivity or susceptibility are obtained, especially related to the Delta variant circulating widely in August and September 2021, that new information may be more accurate.

major vectors of spread for COVID-19, given their greater propensity for social mixing and risky behavior in terms of respiratory pathogen spread (Li, X. et al., 2020; Viner et al., 2021; Wu et al., 2020).

A validated mathematical model of school outbreaks demonstrated that shortening the school week significantly reduced the lengths of both influenza and COVID-19 outbreaks, while post-fever isolation policies were less effective (Burns and Gutfraind, 2020). For influenza, a 1- or 2-day post-fever isolation policy reduced the median attack rate substantially (29 percent and 70 percent, respectively), while shortening the school week reduced the rate by 93 percent for a 3-day week and 73 percent for a 4-day week. For COVID-19, the post-fever isolation policy was much less effective in reducing the attack rate (2 days: 10 percent; 14 days: 14 percent) than a 4-day (57 percent) or 3-day (81 percent) week.

A decision-analytical modeling study attributed most COVID-19 cases in schools to community acquisition rather than within-school transmission. Furthermore, changes in case numbers associated with school reopening were smaller than those linked to community-based non-vaccine control interventions (Naimark et al., 2021). However, at the time of this report, many countries have only just reopened in-person schooling, so evidence is insufficient on the impact of that choice, whether schools are a driver or dominant environment for transmission, and whether children are now bringing home the virus and transmitting to family members. More research in this area is warranted, especially on multigenerational households with certain individuals who may be more susceptible. As many countries begin grappling with how to reopen schools and resume in-person classes, it will be necessary to ensure they have the physical capabilities to do so safely, including water, sanitation, and hygiene services and flexible learning environments. In Senegal and Niger, only 22 and 15 percent, respectively, of schools have access to basic handwashing (UNICEF, 2020). However, while keeping schools closed may keep them safer from the virus, development experts highlight the negative consequences for children’s learning in low- and middle-income countries. The longer children are out of school, the more likely they are to drop out and the higher their risk of recruitment by armed groups or early marriages for young girls. It will be important for governments to consider these needs in their pandemic response, including the economic consequences that families face due to business closures. Many families may have trouble finding the money for school fees, so even when reopened, schools may have fewer students to support teachers and other staff. Better understanding of whether schools are driving transmission as they reopen, and what interventions are most effective, especially in low-resource contexts, will be critical to maintaining safe education for millions of children.

Non-School Venue Closures

The impact of closing non-school venues (e.g., bars, restaurants, gyms, entertainment venues) on respiratory virus transmission is difficult to quantify. However, both COVID-19 and influenza are statistically overdispersed—with large proportions of their caseloads attributable to a number of large clusters—which makes communal settings places where substantial numbers of infections could potentially occur. For instance, indoor dining at restaurants is associated with greater risk of transmission, because people eat and drink without masks. U.S. CDC has reported that in March–December 2020, U.S. counties permitting on-premises restaurant dining experienced increases in daily COVID-19 case growth and death growth rates 41–100 days and 61–100 days afterward, respectively (Guy et al., 2021b). A study in Hong Kong showed most transmission occurred in mask-off settings, such as restaurants (Martín-Sánchez et al., 2021). Similarly, a modeling study compared real-time trends in movement patterns based on cell-phone data with the rate of new COVID-19 infections in 25 high-incidence U.S. counties, finding that reduced mobility (i.e., physical distancing) was strongly correlated with decreased case-growth rates in most of the counties (Badr et al., 2020). The overall efficacy of measures such as business closures depends highly on whether the facilities have indoor versus outdoor or combined outdoor-indoor settings. Full closure may not be necessary for those with an outdoor option, but then the season and geographical location will play a role in successful implementation.

Testing

Molecular tests can be effective diagnostics during a pandemic, but they are limited by production capacity and the time needed to obtain results—which is problematic in the context of a highly transmissible virus—although antigenic tests may be able to overcome those challenges. This underscores the need to strengthen testing preparations before a pandemic by considering community-specific factors, such as determining which types of tests to use, ensuring they are available and affordable, and reducing the time from testing to result (Peeling and Olliaro, 2021; Peeling et al., 2021). A meta-analysis of studies on influenza diagnostic tests showed that in adults and children, both novel digital immunoassays and rapid nucleic acid amplification tests had substantially higher sensitivities for influenza A and B—with similarly high specificities—than traditional rapid influenza tests (Merckx et al., 2017). The correlation between the results for rapid influenza diagnostic tests and molecular tests for H1N1 influenza is relatively poor, but the Winthrop-University Hospital Infectious Disease Division’s Diagnostic Swine Influenza Triad of nonspecific laboratory indicators can

be used to make a rapid clinical diagnosis in hospitalized, symptomatic patients with negative rapid test results (Cunha et al., 2010).

During the COVID-19 pandemic, testing asymptomatic individuals at high risk (e.g., residents of aged care or skilled nursing facilities, passengers on cruise ships, personnel on military ships) has had a high positive yield (Kasper et al., 2020; Kimball et al., 2020; Oran and Topol, 2020). Despite little evidence to support mass testing without risk-based targeting, testing in combination with tracing and travel-related quarantine can be effective. A probability model theorized that testing on both entry and exit from quarantine can reduce the duration of 14-day quarantine by 50 percent and yield the greatest reduction in post-quarantine transmission events (Wells et al., 2021). South Korea, China, and Singapore have used digital contact tracing to control the spread of COVID-19, although this strategy raises privacy concerns and can be hampered by technical issues (Lancet Digital Health, 2020).

A modeling study estimated the impact of school reopening under various testing and tracing scenarios in the United Kingdom in September 2020, finding that a comprehensive test-trace-isolate strategy would be needed to avoid a second wave of COVID-19 (Panovska-Griffiths et al., 2020). If schools reopened full time and 68 percent of contacts were traceable, avoiding the second wave would require testing an estimated 75 percent of symptomatic cases and isolating positive cases. If only 40 percent of contacts were traced, 87 percent of symptomatic cases would need to be isolated. The authors posit that without such widespread testing and contact tracing, school reopening coupled with relaxing the lockdown measures would likely engender a second wave with an R that exceeds 1. However, other modeling research suggests that test-trace-isolate strategies alone have been insufficient without complementary measures, such as distancing and improved hygiene (Contreras et al., 2021). Lastly, modeling has shown that 62 percent of simulated transmissions occur in the presymptomatic phase for SARS-CoV-2, compared to 10 percent for influenza (Goyal et al., 2021), suggesting that testing asymptomatic individuals may have less applicability to influenza.

Case Isolation and Quarantine

If implemented early, isolation and contact tracing can be effective in controlling the spread of COVID-19, although these strategies may be less effective for influenza given its shorter incubation period. A mathematical modeling study estimated that in most scenarios, the combination of highly effective case isolation and contact isolation (supported by contact tracing) is sufficient to bring a new outbreak of COVID-19 under control within 3 months (Hellewell et al., 2020). However, another study modeled

the impact of case isolation and contact tracing in combination with other measures and found that adding moderate physical distancing measures would be more likely to achieve control; otherwise, achieving an Rt less than 1 would require isolating and contact tracing for very high proportions of cases (Kucharski et al., 2020). The findings of a rapid review of 29 studies indicate that quarantine contributes importantly to reducing COVID-19 incidence and mortality when implemented alone but is even more effective in combination with other measures, such as school closures, travel restrictions, and physical distancing (Nussbaumer-Streit et al., 2020). However, quarantines are logistically difficult to impose and can have adverse mental and physical health effects on individuals required to isolate for extended periods.

A summary of the evidence of various governmental and public health measures explored in this chapter (see Table 3-3) and a list of potential research topics that need additional study in this area (see Box 3-3) are outlined below.

* “Efficacy” refers to data from RCTs; “effectiveness” refers to data from experimental or observational epidemiologic studies.

EVIDENCE FOR COMBINATIONS OF MEASURES

Evidence from a large-scale review and other sources suggests that combinations of non-vaccine control interventions are more effective in curbing the spread of infectious respiratory viruses than single interventions in isolation. Furthermore, U.S. CDC recommends a layered approach of deploying public health measures for different thresholds of community transmission (CDC, 2021a). A review that quantified the impact on the effective reproduction of COVID-19 of more than 6,000 non-vaccine control

interventions across 79 territories suggests that no single intervention alone can halt the spread of SARS-CoV-2; instead, an appropriate combination is needed. The authors identified several interventions that significantly contributed to reducing Rt to less than 1, including curfews, lockdowns, and closing or restricting settings where people gather in smaller or larger groups for extended periods (Haug et al., 2020). This has been underscored by other studies showing that non-vaccine control interventions (e.g., moderate physical distancing measures, self-isolation, contact tracing) need to be used in combination for maximal effectiveness (Kucharski et al., 2020). Similarly, a hospital in Australia reported that diagnoses of SARS-CoV-2 and other respiratory viruses plunged after travel bans in conjunction with physical distancing (Marriott et al., 2020). In Taiwan, infectious respiratory diseases declined by 50 percent during the early phases of the COVID-19 pandemic compared to historical data from past influenza seasons. This decline has been attributed to a combination of universal hygiene interventions (e.g., handwashing, cleaning high-touch surfaces, ensuring access to medical-use alcohol) and mass masking policies that were complemented by strategies to educate the public about masks, ensure access to masks, and strongly encourage mask wearing in public (Hsieh et al., 2020).

OVERARCHING EVIDENCE

Most non-vaccine interventions currently have limited, mixed, or low levels of RCT evidence (WHO, 2019), although many have non-RCT evidence. Evidence for many of these interventions is by necessity ecological or observational, as it would not be possible or ethical to test some of them (e.g., lockdown, border closure) by RCTs. Furthermore, the science required for understanding of human respiratory emissions is experimental and has generated a body of robust evidence that is not well captured by evidence-based medicine frameworks. Some such evidence for respiratory aerosols is rooted in basic physical principles, which are as predictable as the effect of gravity, and does not require validation by RCTs. Additionally, the scientific community has found great success with the scientific method and laboratory experimentation for certain fields with a notoriously low tolerance for error. This pandemic has highlighted the interdisciplinary nature of infectious disease outbreaks, so the available overarching evidence guiding policy decisions and recommended interventions should also reflect that multi-sectoral influence. However, current research funding and opportunities remain largely siloed and are limited to efforts within certain fields. Without more integration, progress in understanding the intersection of these critical fields might not occur. This type of detailed development and quality evaluation research must occur between pandemics, not once they have already begun.

Some relatively robust studies provide overarching evidence about the synergistic effects of certain combinations of non-vaccine control measures in curbing the spread of both COVID-19 and pandemic influenza. Using longitudinal regression, a review of the literature found strong evidence for an association between school closures, internal movement restrictions, and reduced Rt (Liu et al., 2021). Workplace closure, income support, and debt/contract relief had strong evidence of effectiveness if levels of intensity were not taken into account. Cancellations of public events and restrictions on gatherings had strong evidence of their effectiveness but only when implementation at maximum capacity was evaluated—for instance, restrictions were not effective for gatherings of greater than 1,000 people but were effective for less than 10 people. The focus of effectiveness in this chapter is measures’ abilities to reduce virus transmission; the next chapter explores social, economic, and other contextual factors that can affect the implementation and overall population optimization of these measures.

A systematic review of pandemic influenza mitigation literature reported that vaccination appears to confer significant protection against infection but evidence was insufficient to identify appreciable protection from antiviral prophylaxis, seasonal influenza cross-protection, or various non-vaccine control interventions in isolation. The authors propose that an optimal strategy would likely feature a layered combination of interventions (Saunders-Hastings et al., 2016).

According to a modeling study based on daily data from 175 countries, public event cancellations, private-gathering restrictions, and school and workplace closures significantly reduced the number of COVID-19 infections, even after controlling for additional lockdown policies that were in place (Askitas et al., 2021). Restrictions on internal movement and public transport had no such effects—likely due to lockdown policies—while less-stringent restrictions on international travel imposed early in the pandemic had a short-lived effect.

CONCLUSIONS

Overarching

It is important to introduce public health interventions in combination as a layered preventive approach to maximize the reduction in the risk of transmission. A number of factors should be considered when determining the approach that is best for a particular setting to reduce harm to livelihoods, including the effectiveness of measures in reducing viral transmission as well as economic and other contextual factors.

There is a need for a research framework to address the gaps in evidence for particular public health interventions that takes into account

that the way evidence is best assessed for each measure may differ, since some interventions cannot be tested in a randomized controlled trial (RCT) that assesses measures in combination as well as separately and that tests mandates for influenza. This should consider that some science, such as aerosol and physical sciences and engineering, provides the best evidence for specific questions and that in some cases interventions (e.g., national border closure) cannot be tested in RCTs because doing so is not feasible or ethical, so that ecological or observational studies would be required. Better integrating research in these different fields can inform not only various methodologies but also more complete understanding of interventions and impacts.

Individual-Level Actions

Multiple lines of evidence show that face masks are effective in reducing COVID-19 transmission, and face masks should also be effective for influenza. For seasonal influenza, jurisdictions could consider a mandate depending on the setting and the incidence and severity of circulating strains. For example, masks could be mandated in hospitals during the influenza season. During a pandemic, appropriate types of masks and their use should be mandated, in part because they are less costly and less disruptive than other interventions and may avert the need for a costly lockdown. The best-performing masks consist of suitable materials with high filtration efficiency, fit well with no leaks, and have a low pressure drop for ease of extended use and breathability.

Face shields are intended to be worn over masks and are used in medical settings to avoid splatter. They do not reduce exposure to aerosols. They are not a substitute for masks in the community, businesses, mass gatherings, or modes of transportation, including cars, buses, trains, ships, and airplanes. Their effectiveness when used alone is limited at best.

Physical distancing measures, overall, have some evidence for effectiveness. Distancing of 1–2 m reduces but does not eliminate transmission. Factors such as airflow direction, duration of exposure, and use of masks and other interventions influence the efficacy of physical distancing.

Building and Environmental Controls

Among the types of building and environmental controls evaluated during COVID-19 that may have applicability for influenza, ventilation/filtration systems have the most evidence of demonstrated effectiveness in reducing virus transmission. The World Health Organization and professional organizations need to develop evidence-based guidelines for ventila

tion and filtration during a pandemic, and the relevant authorities in each country around the world need to incorporate these into their building standards. Short-term mitigation measures, such as air purifiers and information on proper use to avoid negative airflow patterns, should also be made available.

Transparent barriers alone are effective only in the specific scenario of a brief, face-to-face interaction involving two people; in fact, barriers may be harmful because they can create “hot spots” where particles accumulate and impede proper ventilation in a room. Masks are preferred because they remove particles, whereas barriers simply divert them.

Government and Public Health Controls

Studies during the COVID-19 pandemic produced evidence that highly restrictive, mandated measures, such as curfews and lockdowns, were effective in reducing virus transmission. They can be expected to produce similar results for influenza, but any decision to impose such measures would need to take into account their disruptive effects on personal life and the economy during the current pandemic.

Since the SARS-CoV-2 virus had been spread by travelers to a number of countries before the World Health Organization recognized the novel coronavirus as a Public Health Emergency of International Concern—and even more so, before it declared COVID-19 a pandemic—there is little evidence that the restrictions on cross-border travel that many countries imposed were effective in reducing viral transmission during COVID-19, as is likely to be true in an influenza pandemic as well. Nonetheless, border closures—for example, by island nations—can be effective when imposed before community transmission is established, provided that any persons allowed to enter are quarantined, as should be true for all entrants who have recently been in countries where the virus is known to be present.

There is some evidence during COVID-19 that children are not the main drivers of SARS-CoV-2 transmission, unlike influenza, where children play a major role in transmissibility in the community because they shed virus for longer and at higher levels. Hence, school closures may be more effective during an influenza pandemic at reducing virus transmission compared with during COVID-19; however, given the continued emergence of COVID-19 variants, such as Delta, vigilance in monitoring the transmissibility among children is needed.

Evidence from the COVID-19 pandemic suggests that closing indoor venues, such as restaurants and churches, where people do not wear masks all the time (i.e., while eating, drinking, singing) may reduce virus transmission, but the emergence of recent variants of concern may influence the effectiveness of this intervention.

For mask mandates to be effective, public health agencies need to communicate clearly with the public about the value of particular types of masks, how to use them correctly, and when and where they should be worn.

The combination of testing, case isolation, and contact tracing has documented effectiveness for reducing transmission of COVID-19, especially when implemented early, but this strategy may be less effective for influenza due to its short incubation period. Although the evidence is incomplete, mass testing that is not targeted to groups at highest risk has not been shown to be effective in reducing viral transmission.

RECOMMENDATIONS

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