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National Academy of Medicine; National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Global Health; Committee on Public Health Interventions and Countermeasures for Advancing Pandemic and Seasonal Influenza Preparedness and Response; Schenk E, García P, Capron A, editors. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington (DC): National Academies Press (US); 2021 Nov 17.

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Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19.

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6Concluding Thoughts

The prediction that a severe respiratory virus outbreak could be “potentially the most devastating global health events with far-reaching consequences” (WHO, 2019a) was confirmed in 2020, which was dominated by the coronavirus disease 2019 (COVID-19) pandemic. Yet, even as parts of the world begin to overcome that pandemic and other parts struggle with surging infection due to variants of concern, the looming threat of seasonal and pandemic influenza remains. That poses the urgent question: what can be learned from the pandemic that might improve national and global response to future influenza events? One lesson is that, even with extraordinary effort and massive resources, vaccines take time to develop, test, and produce and are not a panacea for curbing a pandemic of a novel pathogen. Effective strategies to prepare for and respond to novel respiratory viruses, including influenza, must therefore also include comprehensive and coordinated surveillance to detect, trace, and quantify the virus; non-vaccine interventions to reduce viral transmission; and innovative, international means to discover and test therapeutic agents that can diminish morbidity and mortality and protect health systems and the wider society.

PRIORITIZING NON-VACCINE PUBLIC HEALTH INTERVENTIONS

Based on the study analyses, the committee reached a number of key conclusions that reaffirm the importance of non-vaccine control measures in preparing for and responding to a respiratory virus event. The committee recognized that plans should take into account a range of measures, from implementing early detection of a pathogen of pandemic potential to lessening morbidity and mortality and from mitigating transmission during the outbreak to reducing the personal, social, and economic disruption that can be caused by public health interventions.

The study concluded that countries need to bolster surveillance capacity in order to detect cases, trace contacts, and quantify viral spread during a potential outbreak (see Table 6-1)—especially looking for currently unexpected and typically unobserved pathogens that could signal a pandemic. Many major emerging infectious disease threats—including coronaviruses and influenza viruses—have zoonotic origins at the interface of humans and wild or domesticated animals; others are shaped by environmental conditions (such as vector- and water-borne diseases) or other sources. COVID-19 underscored the need for broader implementation of collaborative and coordinated approaches (e.g., One Health) to conduct expanded surveillance at the nexus of multiple disciplines. Core surveillance capacities could also be broadened to take advantage of technological developments, such as open-access electronic data streams, digital mobility data, and sewage surveillance, all of which can provide early warning signals of disease outbreaks. Ensuring the integrity and validity of surveillance data collection and analysis is also critically important; the committee recognized that such data obtained during COVID-19 sometimes suffered from ascertainment biases and were not always collected or shared efficiently.

Non-vaccine control measures—such as face masks, distancing, and lockdowns–are used to help mitigate the spread of respiratory viruses. This study analyzed scientific evidence for the effectiveness of the most widely used measures, taking into account factors that can affect their population implementation. However, an intervention's overall effectiveness depends on both its ability to reduce virus transmission and population uptake; factors related to both need to be considered when deciding whether to recommend an intervention for a particular setting. The committee favored a layered approach in which measures are combined in a way that reduces harm to lives and livelihoods. For instance, masks are less costly than other interventions and could be recommended prior to other strategies, such as border restrictions, lockdowns, and curfews, that have wider economic ramifications in terms of job losses and disruption of people's lives. The committee recognized, though, that border restrictions and related measures were effective for some countries in holding down transmission early in the pandemic, and countries and global health agencies should consider these alongside their potential economic effects.

The committee noted that many non-vaccine control measures cannot be appropriately studied by methods conventionally considered to be “the gold standard,” such as a randomized controlled trial (RCT). For instance, lockdowns cannot be imposed in a randomized fashion, and RCTs face difficulties in accounting for the myriad contextual factors that ultimately affect the outcomes produced by different measures in diverse communities. For certain measures, science and engineering studies offer the appropriate means of obtaining valuable information about efficacy. Hence, the committee identified the need for a research framework to address the gaps in evidence for non-vaccine public health interventions that take into account the way evidence may best be assessed for each (see Table 6-2).

TABLE 6-1Study Conclusions on Surveillance (Chapter 2)

Detection of potential threatsCOVID-19 has further emphasized the need to use the One Health approach to better target surveillance, including by building on currently existing platforms for influenza surveillance in wild birds, poultry, and livestock. This includes programs for detection of new zoonotic strains with pandemic potential and large antigenic drifts and shifts and research to better understand the pandemic potential of new strains.
One Health programs need to identify new viral strains, assess the risk they pose to people, and analyze where cases are likely to be found and outbreaks are likely to begin. Interdisciplinary collaboration among U.S. agencies, academic institutions, national governments, and multilateral partners has been successful in performing this surveillance in several countries with a One Health approach.
Quantifying the spread of a pandemicData informing public health surveillance, including influenza and COVID-19, are vulnerable to ascertainment biases and therefore may not reflect the true underlying epidemiology; these biases happen particularly as a novel strain is first emerging. When the means used to collect data cannot be changed to avoid these problems, they can be taken into consideration during the analysis and interpretation of data being used in policy decisions. If not corrected, these biases can misinform the public about a disease's impact and the likely effects of public health interventions in general and in particular subgroups.
Within countries, sharing of data collected from community-based surveillance is critical for identifying the likely impact of outbreaks. Inefficiencies in collecting and sharing all types and sources of data among countries and global health agencies hampered the flow of information during the COVID-19 pandemic. The rapid sharing of a wide range of data internationally, including syndromic, epidemiologic, clinical, pathogen specific (e.g., genomic), and other (such as open-source intelligence), can provide early warning of an outbreak of concern, as well as a picture of how it may develop.
Tracing the arrival and community transmission of a virusCOVID-19 showed that countries and intergovernmental bodies need to bolster their surveillance capacities, especially the ability to look for the unexpected and unobserved and sustain surveillance during disease surges. These systems can be strengthened by being repeatedly challenged to assess their ability to detect novel threats. Gaps identified can then be followed through and retested iteratively before an actual incident. Current surveillance approaches and tools are designed and more suitable for monitoring of known pandemics or ongoing surveillance for seasonal influenza than for the early detection of a pandemic-capable pathogen before widespread transmission.
COVID-19 showed that the set of core capacities should be broadened to take advantage of technological developments, including but not limited to, digital mobility data, sewage surveillance, and monitoring of open-access electronic data streams (digital surveillance), as well as to maintain a stockpile of basic supplies (such as nasal swabs) that will be needed to conduct tests.
Full reporting of surveillance data, to both higher authorities within a country and to international agencies, is sometimes impeded by negative political or economic repercussions. For example, disciplining local officials for reporting novel pathogens disincentivizes health surveillance. The first step in eliminating such barriers is to recognize their existence; such recognition can come from the parties involved or from observers. Unless such barriers are removed, reporting structures cannot provide complete, accurate, and timely information about possible disease outbreaks.
Harmonization of information from multiple data sources is essential for quickly identifying the origins and spread of novel agents and strains and for providing useful information for decision makers and the public. Harmonization rests on the development and use of instruments to standardize the data. When diverse data come from many sources and reflect clinical and public health differences at the local level, particularly in the early stages of a pandemic, organizations that collect the data may be able to develop means of standardizing the data after they have been submitted.

In analyzing the ways that responses to COVID-19 may be applicable to influenza, the committee found that face masks are not only relatively simple and inexpensive to make but, when well fitted to the wearer and containing multiple layers of materials with high filtration efficiency, very effective at reducing transmission. On the other hand, the available studies indicate that barriers and face shields worn without face masks are ineffective and hence inadvisable because they give a false sense of security and use resources that could better be devoted to improving the implementation of efficacious measures. Moreover, airflow can play a significant role with respiratory viruses, so proper building ventilation and filtration systems are critical to reducing transmission. In terms of differences in transmission, children—who usually have mild symptoms (or none) when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may not contribute much to the COVID-19 pandemic—are typically major factors in the spread of influenza viruses. School closures may thus be more effective in mitigating an influenza event than COVID-19. However, the ongoing emergence of variants, especially Delta in summer 2021, may change this finding.

While non-vaccine interventions are backed by scientific evidence, their successful implementation requires input from and support by multiple actors. Recommending non-vaccine control measures for a particular setting should take into account not just their effectiveness in reducing virus transmission but also the setting's culture, norms and beliefs, political systems, and other contextual factors. Recommendations should also consider the flexibility to adapt interventions that are effective in one setting but not feasible in another (e.g., physical distancing in high-density urban areas) (see Table 6-3). The COVID-19 pandemic showed the critical influence of the behavior of and communication from leaders—particularly within governments—on the population uptake of public health interventions. In many settings, trust in such elected leaders was undermined when policies did not rest on a strong evidence base or official mandates seemed to run counter to scientific findings. Countries, agencies, and organizations at the national, regional, and global levels will need to reevaluate methods for encouraging populations to adopt and follow public health measures, understanding target populations to encourage intervention uptake, instilling trust in leaders, and strengthening scientific research. The cyclical process of investigating successes and failures to improve implementation of public health interventions necessitates effective collaboration, clear communication, and strong partnerships between leaders in the domains of policy science. Hence, evidence should be generated that can be used across settings to inform, promote, and monitor intervention implementation.

TABLE 6-2Study Conclusions on Effectiveness of Non-Vaccine Control Measures (Chapter 3)

OverarchingIt 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, because some interventions cannot be tested in a 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 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 actionsMultiple 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, masks 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 meters 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 controlsAmong the types of building and environmental controls evaluated during COVID-19 that may have applicability for influenza, ventilation/filtration systems have the most demonstrated effectiveness in reducing viral transmission. The World Health Organization (WHO) and professional organizations need to develop evidence-based guidelines for ventilation 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 controlsStudies 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.
Because the SARS-CoV-2 virus had been spread by travelers to a number of countries before WHO 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 among the main drivers of SARS-CoV-2 transmission, unlike influenza, where children play a major role in community transmissibility, because they shed virus for longer and at higher levels. Hence, school closures may be more effective during an influenza pandemic at reducing 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 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.

If control measures fail and people become infected with a respiratory virus, the focus shifts to mitigating morbidity and mortality with therapeutic agents. COVID-19 exposed a number of critical gaps pertaining to the global capacities to stock, scale up, and allocate such drugs, including supplies needed for their delivery (see Table 6-4). This study reinforced the need to develop a framework to guide allocation of scarce therapeutic resources for patients in a health system in a way that alleviates the decision-making burden on health care providers, such as through the crisis standards of care framing referenced previously. However, these conversations need to happen well before an outbreak begins and cannot be left to chance. They require directed and focused policy shifts in research and infrastructure priorities as well as diverse community and public engagement to inform the prioritization of scarce resources.

The COVID-19 pandemic also emphasized the potential therapeutic benefits of repurposed drugs, initially developed for other diseases, and the advantages of rapid research on the efficacy of therapeutics during a pandemic via adaptive platform trials. Research efforts highlighted the feasibility and necessity of collaborative international platforms and innovative partnerships focused on developing treatments for existing and novel respiratory viruses.

A WAY FORWARD

Besides reaching conclusions and recommendations regarding preparing for future respiratory virus outbreaks, this study also brought to light important areas of work that remain to be explored and that, indeed, go beyond what we are able even to fully enumerate. Any number of reasons account for this gap in knowledge. Foremost among these is that the first response of governments, health care personnel, and scientists alike was to employ public health countermeasures against the novel coronavirus and use available therapies to treat its victims. Given the nature of the pandemic, innovation in both public policies and clinical practices quickly became a necessity, especially give the inadequacy of existing preparedness plans and the shortages in many essential supplies. But, in most settings, it took some time before such trial-and-error attempts to control the spread of the virus and respond to its effects were supplemented by explicit efforts to study what was happening and formally evaluate the effectiveness of alternative measures and policies. As the committee carried out its inquiry and prepared its conclusions and recommendations, increasing numbers of research findings—from physical and implementation scientists, as well as from clinicians and epidemiologists—began appearing in the peer-reviewed literature. These studies have provided answers to some questions but also reveal issues—some not previously perceived—that need to be addressed. This massive amount of data that has emerged throughout the pandemic has also elucidated the need for streamlined health data from across countries that can quickly be tapped to inform decisions and policies, and ensure they are rooted in evidence and equity. Together with private-sector technology partners, the World Health Organization launched the World Health Data Hub1 to transform data and provide a secure, transparent environment for predictive analytics and data visualization. If successful, this collaboration could be tremendously helpful during the next pandemic and help the world to avoid the lags in understanding the big picture of an outbreak, as was the case during the early months of 2020.

TABLE 6-3Study Conclusions on Implementation of Non-Vaccine Measures (Chapter 4)

Optimizing intervention adherenceThe COVID-19 pandemic demonstrated that a number of contextual factors, including political systems and leadership styles, culture, individual norms and beliefs, and the methods used to implement public health policies, influenced the uptake and optimal execution of public health interventions. This suggests a need to conduct research to ascertain how all these factors affected public acceptance.
Leadership and community engagementPublic trust in government officials, community leaders, scientists and other experts, and other people who influence public opinion has affected—both positively and negatively—public response to governmental policy announcements and mandates and the uptake of non-vaccine interventions to slow the spread of COVID-19. Trust in such persons and confidence in what they said about interventions was undermined when the policies were shown not to rest on a strong evidence base, the reasoning behind the policies was not well communicated, and when the personal behavior of such persons did not coherently and consistently adhere to the practices that they had recommended or required.
Data and frameworksThe variety of interventions implemented in response to the COVID-19 pandemic has not always been informed by evidence of effectiveness but, in some cases, has been based on contextual factors and policy makers' individual views. This experience highlights a need to both generate evidence that is relevant across a wide range of settings and use this evidence when implementing non-vaccine control measures.
Historically, investments in research to evaluate strategies and means of implementing non-therapeutic and non-vaccine control measures have not been sustained over the long term. The boom-bust cycle of interest in these topics, which peaks with the onset of an epidemic or pandemic, needs to be replaced by longer-term vision and infrastructure building to enable research on all aspects of prevention and response, including non-vaccine and non-therapeutic measures.

TABLE 6-4Study Conclusions on Therapeutics (Chapter 5)

Global pandemic preparationCOVID-19 illustrated critical gaps in preparation to distribute the therapeutic resources needed to care for infected patients in a respiratory viral pandemic, including antiviral medications, oxygen, and equipment necessary for the delivery of supportive care (e.g., ventilators, personal protective equipment [PPE]). Most documentation on stockpile inadequacies focused on the lack of ventilators and PPE, with less transparency around the adequacy of country stockpiles with regard to other therapeutic supplies.
COVID-19 emphasized a need to take a global view of the preparation for pandemic influenza, including the capacities of countries around the world to manufacture, stockpile, mobilize, and scale up therapeutic resources, as well as to conduct research on the effectiveness of therapeutics.
Pandemic responseCOVID-19 demonstrated the need for a framework to guide distribution of scarce and/or novel therapeutic resources in the most rational and equitable way. That framework needs to allow for adjustment based on disease prevalence, pathogen type, mode of transmission, mortality rates, and impacted populations, but universal principles will help in both insulating frontline providers from difficult resource allocation decisions and preventing health care systems from collapse.
Therapeutics researchResearch during the COVID-19 pandemic has emphasized the potential benefits of “repurposed” therapeutics initially developed for another disease. Going forward, maintaining libraries of drugs that show antiviral effects and that have completed safety testing in humans could serve as a starting point for therapeutic research during a pandemic. It will also be important to test drugs—separately and in combination—that act on targets that respiratory viruses have in common (e.g., possible broad-spectrum inhibitors of RNA polymerase, an enzyme common to both COVID-19 and influenza). COVID-19 has also demonstrated the benefits of therapeutics that target exacerbated host response rather than the virus itself (e.g., steroids, tocilizumab). Continuing to evaluate host factors that might impact the severity of respiratory viral infections, either because they are required for viral replication or because they are involved in exacerbated response, could be beneficial in developing therapeutic approaches with broad applicability.
Open repositories, which include negative research results, need to be maintained and shared in order to identify effective public health measures of prevention and assessment and to ensure resources are effectively used rather than used for repeated assessment studies.
COVID-19 has shown the necessity of ongoing research focused on treatment of both existing and novel respiratory viruses, including those that cause seasonal and pandemic influenza, and has highlighted the success of collaborative efforts and innovative partnerships. Work done during the COVID-19 pandemic, including the Solidarity program, has demonstrated the feasibility of research efforts that integrate government programs, private companies, and public–private collaborations and that involve research institutions cooperating internationally.
COVID-19 has shown the feasibility of performing rapid research on therapeutic efficacy during a pandemic through the use of adaptive platform trials with common global protocols, adding and deleting interventions in light of accumulating evidence. The REMAP-CAP, RECOVERY, and Solidarity platforms all demonstrated that this type of trial platform has many advantages, including the ability to adjust study enrollment, include patients from many countries to achieve sufficient power to make evidence-based treatment recommendations more quickly, react to changing evidence prior to study conclusion, and compare interventions to one another, singly and in combination. Being able to build on this work could also expedite the development of evidence-based treatment guidelines when a novel pathogen is identified. In the COVID-19 pandemic, use of unproven therapeutics in an early evidence vacuum led to patient harm, which can be avoided if professional organizations and health authorities encourage clinicians to emphasize study participation from the beginning of an outbreak when previously validated therapeutic options are lacking.
The ability to perform adaptive trials during future pandemics could be improved by putting infrastructure in place that would allow for accelerated regulatory approvals and access to trials of therapies. This is especially important for therapeutic trials that must be conducted in multiple sites in different countries, since rounds of scientific and ethics review can otherwise take years. Establishing networks of high-quality clinical trial sites and developing and obtaining preapproval for generic study protocols from scientific and research ethics committees across all sites could allow for more rapid study enrollment and results.

A second reason for the gap in knowledge is the uneven availability of scientific and financial resources among the world's nations. It is hardly surprising that most of the early research on the pandemic—and now, the first publications—came from high-income countries, even though knowing what worked well or poorly in low- and middle-income countries (LMICs) is essential. After all, ending a pandemic requires implementing effective responses in all settings around the world. Equally important, careful studies of the public health and clinical interventions used in resource-constrained settings can provide data that are also useful in making policies in wealthier settings. It is worth keeping in mind (as described in Chapter 2) that the countries with the highest health security preparedness scores on the Global Health Security Index had some of the poorest performances during the pandemic in terms of detection response times and mortality outcomes (Haider et al., 2020); this finding is in accord with the results of other preparedness assessments. Researchers should examine this disconnect to improve the ways that preparedness plans are developed and used during a pandemic and strengthen the means used to assess whether such plans are sufficient for a strong response.

The broad nature of this study's Statement of Task naturally produced some recommendations that are similarly broad. Further research is needed to analyze and expand the evidence base for each of the study topics in more detail. For example, with regard to our recommendation that surveillance systems should regularly be challenged and strengthened, more study is required to determine the best methods for doing so. In terms of formulating and executing public health policies and pandemic countermeasures, implementation science can be used to further elucidate the specific public health interventions that are most appropriate in particular settings and consider the logistical, social, and economic needs of specific populations. The variety of means that people use to share information (and misinformation) has challenged countries' efforts to disseminate the most current and scientifically accurate guidance to the public; further research will be needed to explore how governments can best communicate changes in policy and mandates based on the evolving evidence base. Appropriate research methodologies are needed to evaluate both public health interventions and use of new or repurposed therapeutic agents in a pandemic setting. The committee also noted the difficulty in further defining and operationalizing how to rationally and equitably distribute therapeutics; such a question merits further attention and will not have a universal answer.

It will also be important to evaluate which COVID-19-related interventions were both effective and have broader applications, including for future influenza pandemics. It is essential to remember that evidence regarding the effectiveness of many of the novel therapeutics and non-pharmacologic controls employed during COVID-19 is rapidly evolving. While reliable data remain very scarce, it would be premature to recommend interventions other than the few that rest on a solid base of evidence, such as using masks and avoiding crowded indoor spaces when the virus is still being spread widely in the community. This is especially true in settings where individual and collective resources are scarce and need to be used very wisely.

The COVID-19 pandemic has made it clear that vaccines and non-vaccine measures, including surveillance, community mitigation strategies, and communication and public outreach, are required to control transmission. While the 2017 U.S. Centers for Disease Control and Prevention Pandemic Influenza Plan does include research across several non-vaccine-related areas, many prominent research agendas and initiatives for respiratory viruses focus primarily or even solely on vaccines (CDC, 2017). For instance, WHO's 2019–2030 Global Influenza Strategy, which builds on the knowledge gaps identified in the 2010–2011 WHO Public Health Research Agenda for Influenza, does not address nonpharmaceutical interventions, which underlines the dearth of research initiatives that aim to strategically strengthen the evidence base for non-vaccine control measures for respiratory viruses (WHO, 2019b). However, community availability of COVID-19 vaccinations came more than 1 year into the pandemic. Research regarding the effectiveness of other types of interventions is therefore likely to be essential but was largely lacking at the time of this report. Furthermore, most published evidence comes from the United States and other high-income countries, demonstrating the need for similar, published studies in LMIC settings.

Defining the appropriate evidence by which to evaluate non-vaccine interventions is also complex. For instance, Chapter 3 discusses the need to evaluate non-vaccine control measures through nonconventional methodologies, since many such measures cannot be studied in RCTs. There is considerable variation across the different contexts and settings within which public health interventions are implemented, and controlling for all such variables to conduct an RCT is not feasible. Furthermore, evaluating novel or repurposed therapeutics using RCTs during a pandemic may be neither practical nor the best way to gather evidence rapidly, given the advantages (both scientifically and ethically) of directly comparing interventions, singly or in combination, and the need for global enrollment to achieve sufficient power to draw conclusions and to make the results applicable in diverse settings. Therefore, it would be critical to consider how to overcome the challenges inherent in initiating international studies and collecting data in an outbreak or pandemic context by setting up collaborative research platforms in advance.

Around the world, countries are at various stages in the process of halting and recovering from the COVID-19 pandemic, which harshly revealed the extent to which lessons from prior epidemics were not adequately applied in policy or practice. With the devastating health, social, and economic harm wrought by the pandemic fresh in the public's mind comes an unprecedented opportunity to harness the resulting political will and public support, along with the research capacity and technological advances that were created to overcome the pandemic. As officials launch the efforts needed to prepare for the coming epidemics of novel respiratory viruses, this study demonstrates that policy makers, public health authorities, and other stakeholders should not only plan to rely heavily on non-vaccine control measures for seasonal and pandemic respiratory viruses but also support the research necessary to expand and improve such measures and the means by which they are implemented. A framework is also needed to ensure more rapid incorporation of such research results into more regularly evolving guidelines, so that history does not repeat itself with lessons that were never learned.

This report examined the crucial role of non-vaccine public health strategies in rapidly detecting, tracing, and quantifying a novel respiratory pathogen of pandemic potential when it first emerges. It has shown that, as an outbreak or pandemic evolves but before any vaccines are developed, non-vaccine interventions become the first line of defense for mitigating virus transmission. After vaccines are available, such interventions continue to be simple, cost-effective countermeasures, given that not all localities may have access to vaccines and that vaccines are not completely effective. Finally, this report highlights that when vaccines fail to deliver full protection, therapeutics are the last line of defense to avert the effects of a virus. Recognizing that the arrival of the next novel influenza or other respiratory pathogen is imminent, public health strategists at the global, regional, and local levels need both to prioritize and to improve non-vaccine control measures now.

REFERENCES

Footnotes

1

For more on the World Health Data Hub, see https://www​.who.int/news-room​/feature-stories​/detail/fighting-infection-with-information (accessed August 30, 2021).

Copyright 2022 by the National Academy of Sciences. All rights reserved.
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