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Suggested Citation:"Summary." National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2021. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington, DC: The National Academies Press. doi: 10.17226/26283.
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Suggested Citation:"Summary." National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2021. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington, DC: The National Academies Press. doi: 10.17226/26283.
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Page 2
Suggested Citation:"Summary." National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2021. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington, DC: The National Academies Press. doi: 10.17226/26283.
×
Page 3
Suggested Citation:"Summary." National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2021. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington, DC: The National Academies Press. doi: 10.17226/26283.
×
Page 4
Suggested Citation:"Summary." National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2021. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington, DC: The National Academies Press. doi: 10.17226/26283.
×
Page 5
Suggested Citation:"Summary." National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2021. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington, DC: The National Academies Press. doi: 10.17226/26283.
×
Page 6
Suggested Citation:"Summary." National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2021. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington, DC: The National Academies Press. doi: 10.17226/26283.
×
Page 7
Suggested Citation:"Summary." National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2021. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington, DC: The National Academies Press. doi: 10.17226/26283.
×
Page 8
Suggested Citation:"Summary." National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2021. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington, DC: The National Academies Press. doi: 10.17226/26283.
×
Page 9
Suggested Citation:"Summary." National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2021. Public Health Lessons for Non-Vaccine Influenza Interventions: Looking Past COVID-19. Washington, DC: The National Academies Press. doi: 10.17226/26283.
×
Page 10

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Summary The coronavirus disease 2019 (COVID-19) pandemic has challenged the world’s preparedness for a respiratory virus event, with more than 180 million people infected and an estimated 3.916 million deaths by the end of June 2021 (WHO, 2021). While the world has been combating COVID-19, seasonal and pandemic influenza remain imminent global health threats. Seasonal influenza causes 250,000 deaths on average worldwide each year (Madhav et al., 2017), and influenza remains the circulating pathogen most likely to cause a pandemic. In a given year, the probability of pandemic influenza causing 6 million pneumonia and influenza deaths globally is 1 percent (Madhav et al., 2017). Coronaviruses and influenza viruses have a number of similarities and differences that merit consideration when drawing lessons from the COVID-19 pandemic for influenza events: for example, influenza has a shorter incubation time, and children are usually greater drivers of com- munity transmission (Brownstein et al., 2005). Both before and after a vaccine is available, public health control mea- sures—such as face masks and improved physical distancing—can combat emerging and ongoing influenza outbreaks by mitigating transmission. Non-vaccine measures during the COVID-19 pandemic contributed to shortening the 2019–2020 influenza season by 4–7 weeks in the Northern hemisphere (Stojanovic et al., 2021) and dramatically reducing influenza activity globally (Karlsson et al., 2021), although increased coverage of influenza vaccines and virus–virus interactions may also have contributed. Efforts to combat the effects of seasonal and pandemic influenza can be 1 PREPUBLICATION COPY—Uncorrected Proofs

2 NON-VACCINE INFLUENZA INTERVENTIONS strengthened by drawing on lessons from the COVID-19 pandemic on the need for effective research on, and implementation and sustained use of, non-vaccine interventions. With these issues in mind, an ad hoc committee of experts under the auspices of the National Academies of Sciences, Engineering, and Medicine examined the COVID-19 experience for lessons on the efficacy and imple- mentation of non-vaccine public health interventions and countermeasures to strengthen preparedness for, and response to, future influenza events (see Box 1-1 in Chapter 1). After its deliberations, the committee concluded that a comprehensive, coordinated approach to preparedness and response is required. KEY FINDINGS AND CONCLUSIONS Event Preparedness • Preparedness should include investments to expand holistic strate- gies, such as the One Health approach, to build surveillance capac- ity, improve the accuracy of data collection through defining critical data elements, and develop and maintain data integration platforms to ensure the timely detection of zoonotic pathogen strains with pandemic potential and large antigenic drifts and shifts. • Preparedness efforts should consider the capacities to research, produce, and stockpile therapeutic drugs for respiratory viruses, including any supplies needed for their delivery. • Methods for data collection, monitoring, and adjustments for re- sponse plans should be included in preparedness efforts. • Preparedness efforts should include research into non-therapeutic mitigation strategies and supplies. Event Response • When sociocultural, economic, and other contextual factors are taken into account, non-vaccine control measures offer an effec- tive means of responding to future seasonal and pandemic influ- enza events. To minimize the harm to lives and livelihoods, these measures should be deployed simultaneously in a layered fashion, accompanied by rigorous data collection, monitoring, and adjust- ments to the combination of measures in light of the evidence accumulated. • For non-vaccine control measures to be effective, people must be able and willing to use them, which means that necessary resources PREPUBLICATION COPY—Uncorrected Proofs

SUMMARY 3 and support are distributed equitably and the value that they pro- vide to individuals and the public is communicated clearly. • A critical part of responding to a pandemic is conducting adaptive platform trials and rigorous research of therapeutics. Surveillance and Data Collection Despite the need for proactive efforts to detect a pathogen with pan- demic potential, such as coronavirus, before its widespread transmission, current surveillance tools and strategies are primarily designed to monitor known pandemics and ongoing seasonal influenza. A holistic One Health approach is required to target surveillance more effectively across the do- mains of human, animal, and environmental health. Knowledge gleaned from this type of collaborative, transdisciplinary approach could strengthen the abilities to detect, test, study, and monitor existing and novel zoonotic pathogen strains for antigenic drifts, shifts, and pandemic potential. Suc- cess with this strategy as a part of harmonized and coordinated pandemic preparation and response will depend on countries and intergovernmental bodies adopting a shared commitment to bolstering national and interna- tional surveillance capacities. Contemporary public health surveillance, including testing and contact tracing, uses cutting-edge technologies, such as leveraging mobility data, conducting sewage surveillance, analyzing crowdsourced data streams, and building collaborative tools, including data-sharing platforms and entities. Survey design is key for producing accurate data upon which policy deci- sions are made. It is important to avert biases in designing surveillance, collecting data, and analyzing and interpreting the data in order to provide accurate information to decision makers. Recommendation 2-1: The World Health Organization, the World Bank, and regional public health organizations should work collabora- tively with countries (particularly for low- and middle-income countries and those with extensive animal–human interfaces) to build sustainable capacity for routine surveillance in animals (wildlife, livestock, and domestic), and develop and support interagency One Health platforms. Recommendation 2-2: Countries should institute surveillance as the backbone of their health care systems, which should include submitting aggregated clinical data feeding into public health agencies. To ensure that policy makers have access to accurate, timely, and comprehensive risk assessments, national authorities—with the advice and assistance of regional and global public health agencies—should establish more robust surveillance systems, involving public hospitals and academic PREPUBLICATION COPY—Uncorrected Proofs

4 NON-VACCINE INFLUENZA INTERVENTIONS medical centers, manufacturers of diagnostics, and social network plat- forms. Epidemiologists should be alert to potential ascertainment biases regarding sampling frames and other methodological pitfalls, account for such biases during analysis and interpretation of the data and should notify authorities to take these biases into account and seek support for improving surveillance methods to better achieve represen- tativeness and sufficient geographical coverage. Recommendation 2-3: National public health agencies should both strengthen the capabilities of local and provincial authorities to ac- curately, rapidly, and transparently report data about novel agents and strains and improve their own reporting of data to such regional orga- nizations and global bodies as the World Health Organization and the One Health Tripartite. The global bodies should develop methods to harmonize data from multiple sources, to enable prompt dissemination of useful, comprehensive data, especially to the national and regional organizations that have contributed to the data pool. Organizations to which data are submitted at all levels should work toward removing barriers and disincentives to making full and accurate reports. Recommendation 2-4: The World Health Organization and regional disease control agencies (e.g., European Centre for Disease Preven- tion and Control, Africa Centres for Disease Control and Prevention) should work with countries, and national governments should work with subnational entities (counties, states, provinces), to harmonize, coordinate, and optimize surveillance activities, data collection, and sharing. EFFECTIVENESS OF NON-VACCINE CONTROL MEASURES According to available evidence, when correctly fitted to the wearer, face coverings such as respirators, surgical/procedural masks, and multi- layer woven cloth face masks are the most effective non-vaccine control measure in reducing the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); face shields alone are not effective. Addi- tionally, physical distancing measures have some evidence for effective- ness, but the current recommendations of 1–2 meters do not account for physiology and physics of exhalation flows, their interaction with airflows, and viral particle distribution in droplets and the exhalation cloud. These considerations highlight the importance of ventilation for reducing virus transmission in closed indoor public places where people do not typically wear masks (e.g., restaurants) and the need to integrate the various non- vaccine intervention measures into a more holistic framework, including PREPUBLICATION COPY—Uncorrected Proofs

SUMMARY 5 both individual and community actions. In addition to ventilation, evidence suggests that air filtration may mitigate transmission by reducing virus concentrations in the air in closed indoor places. However, little evidence exists for the effectiveness of barriers, which may even be harmful, if they impede air circulation. The COVID-19 experience has shown that government-mandated con- trols aimed at keeping people apart, such as curfews, lockdowns, and restrictions on gatherings, are effective in reducing viral transmission. Ap- plying this lesson to influenza, it is likely that school closures would be relatively more effective, because children shed influenza viruses for longer and at higher levels than adults. Nonetheless, COVID-19 control measures to limit or prevent contact outside of the home had other social, economic, political, and health effects that have to be balanced when developing poli- cies to mitigate an influenza outbreak. Although mass- and risk-based testing and contact tracing were used in many countries during the COVID-19 pandemic, influenza viruses have shorter incubation periods than SARS-CoV-2, meaning these measures are likely to be less effective for influenza. Measures such as travel restrictions and border closures used by some countries—particularly island nations—were sometimes effective in reduc- ing the spread of COVID-19. However, the World Health Organization (WHO) does not recommend these, because the International Health Regu- lations (IHR), a legally binding framework, do not recommend strict border closures that may impact international travel and trade. To further explore the validity of these conclusions, a research frame- work using diverse evidence from multiple disciplines, such as physical sciences and engineering, is needed to assess individual and combined non- vaccine control measures for respiratory viruses. Ecological and observa- tional studies are required to collect evidence on interventions considered to be too broad or unethical to assess via a randomized controlled trial (RCT). Recommendation 3-1: The World Health Assembly should amend the International Health Regulations to allow countries to use border mea- sures during a pandemic of influenza or other respiratory viruses. Recommendation 3-2: Global, state, and local public health agencies and other entities should mandate wearing face masks that comply with the World Health Organization’s guidance, when justified by the incidence and severity of influenza. Recommendation 3-3: In collaboration with other expert bodies, the World Health Organization (WHO) should develop and disseminate technical recommendations on how to assess and create ventilation PREPUBLICATION COPY—Uncorrected Proofs

6 NON-VACCINE INFLUENZA INTERVENTIONS conditions in various settings that will reduce transmission of respira- tory viruses in various settings. WHO and its collaborators should promote these widely and assist countries in incorporating them into their building standards and implementing them between pandemics. Recommendation 3-4: The World Health Organization—as well as national centers for disease control and prevention and other regional, national, and subnational public health authorities—should recom- mend against the installation of clear plastic or other similar barriers and face shields without appropriate face masks. Recommendation 3-5: Funders should incentivize more integration of research among scientific and medical fields to inform investigations of transmission, prevention, and treatment of influenza and other respira- tory viruses. Such integration should include a standardizing and sharing of language across sectors, and mechanisms for sharing relevant data. Implementation of Non-Vaccine Control Measures A number of social, cultural, structural, and other contextual factors have influenced the public’s reception to and uptake of non-vaccine control measures during the COVID-19 pandemic. Such public responses can be profoundly shaped by a range of beliefs and norms that vary across com- munities around the world; policies and intervention plans need to take these into account when mitigation strategies for respiratory viruses are designed and implemented. The effectiveness and uptake of non-vaccine control measures is ulti- mately contingent on coordination that is spearheaded by strong leadership and coordinated governance and communication. As the COVID-19 pan- demic illustrates, swift, proactive government action and effective harmo- nization within and across sectors—supported by leaders who model the recommended behavior—ultimately influenced public receptivity to and use of such measures. While social, cultural, and other contextual factors play pivotal roles, governments are the primary actors in determining how non-vaccine interventions are communicated and deployed. The COVID-19 pandemic exacerbated the racial, socioeconomic, and other health inequities that affect many people’s lives. These inequities often led to heightened risk of coronavirus exposure due to occupational or living conditions, as well as greater disease severity and mortality fueled by a higher prevalence of comorbidities. Hence, strategies for successful implementation of non-vaccine control interventions should take into ac- count community-specific social and structural determinants of health, particularly by using data and frameworks to measure and ensure the equi- PREPUBLICATION COPY—Uncorrected Proofs

SUMMARY 7 table impact of such interventions, which may require providing resources adapted to overcome existing barriers and inequalities. Recommendation 4-1: Global and regional public health agencies (e.g., World Health Organization, Pan American Health Organization, Africa Centres for Disease Control and Prevention) and national governments, including their local and state health agencies, should adopt policies that are tailored to each affected population, taking into account its social, economic and cultural characteristics, needs and resources, and other contextual factors, including norms, values and beliefs, in order to optimize the implementation of public health interventions, espe- cially those that rely on individual behaviors. Recommendation 4-2: Governments, leaders of departments of health at local, state, and national levels, and elected and appointed govern- ment leaders should: • Take the systemic factors, such as race and socioeconomic dis- advantages that affect the health of affected populations into consideration and leverage behavioral health research and mar- keting tactics when developing and implementing public health interventions; • Demonstrate, in their behavior, adherence to non-vaccine mea- sures to prevent influenza in order to promote public trust in, and uptake of these measures; • Engage the community—including grassroots organizations, spiritual leaders, teachers, and sports coaches—in making and communication decisions about public health measures; and • Choose words to convey communications positively (e.g., “physical distancing,” “social solidarity,” and “stay at home” rather than “social distancing,” “individual isolation,” and “lockdown”). Recommendation 4-3: Funding agencies should create mechanisms to support the rapid application of data and implementation frameworks during an influenza pandemic as well as to enhance similar mechanisms during interepidemic periods. Such mechanisms can be used to support implementation research on non-vaccine control measures for influenza. Recommendation 4-4: National governments—as well as local, state, and global public health agencies—should develop readily imple- mentable intervention plans for outbreaks of influenza and other diseases. Such plans should specify how, from the beginning of an outbreak, the government will PREPUBLICATION COPY—Uncorrected Proofs

8 NON-VACCINE INFLUENZA INTERVENTIONS • Take into consideration the needs of the population affected, with special attention to the needs of marginalized groups; • Iteratively collect and use data about the implementation and effectiveness of non-vaccine control measures to adapt plans where needed; and • Use proven scientific frameworks to guide and improve such measures. Therapeutics As demonstrated by the COVID-19 response, pandemics spur the need to rapidly identify, manufacture, and distribute therapeutic drugs. It also showed the importance of having mechanisms in place that are ready to conduct international collaborative trials of existing and novel therapies, singly and in combination, and of stockpiling any therapeutic agents known to be effective and the supplies that are essential for drug delivery and the full course of care. Guidance is also needed on how to distribute scarce and novel therapeutics equitably and clearly for patient care. Universal principles will need to guide this allocation in ways that build trust by preventing health systems’ collapse and removing allocation decisions from frontline providers. Adaptive platform trials conducted with shared global protocols allow for comparing interventions and adjusting participant enrollment as evi- dence on therapeutics evolve. During a pandemic, these platforms can be leveraged to test promising therapeutics when RCTs may not be feasible. To ensure progress in therapeutic research, global cooperation, coordination, and collaboration should be sustained between governments, private com- panies, and global organizations, perhaps through models such as WHO’s Solidarity trials and data-sharing efforts to obtain evidence on therapeutic safety and efficacy. Recommendation 5-1: National governments should mandate that the appropriate authorities (ministries of health or comparable government agencies): • Regularly evaluate existing stockpiles of therapeutics (includ- ing antivirals, other antimicrobials for treatment of secondary infection, and supportive care treatments, such as oxygen) and other articles needed for care delivery (e.g., personal protective equipment); • Secure sources that can reliably supply all items needed during an influenza pandemic; and • Assess, and establish where possible, local production capabili- ties for all such items. PREPUBLICATION COPY—Uncorrected Proofs

SUMMARY 9 Recommendation 5-2: The government agencies responsible for public health guidance in each country (e.g., United Kingdom Health Secu- rity Agency, U.S. Centers for Disease Control and Prevention) should develop a framework to guide the use and prioritization of treatments that can be flexible with changing evidence during a respiratory viral pandemic. That framework should be able to be adjusted depending on the pathogen, taking into account its transmission route, the at-risk populations, and associated morbidity and mortality rates. The frame- work should identify: • Who will evaluate guidance from global and national health organizations and from professional societies in order to define evidence-based treatment guidelines; • How guidelines for treatment selection and delivery will be communicated to health agencies in the country’s states/prov- inces/regions and to frontline health care facilities, with a focus on avoiding the use of non-evidence-based therapeutics outside of clinical trials; • How suitable places to administer care will be selected, with consideration of options that provide alternatives for care deliv- ery outside of already overwhelmed health facilities and primary care clinics; • Which populations should be the focus for therapeutic delivery with scarce resource availability (e.g., prevention in those not yet infected, versus treatment of those who are mildly or criti- cally ill), who will make those determinations, and how com- munity interests will be incorporated; and • How to distribute a treatment modality equitably throughout the country and among patients including when health systems have moved to crisis standards of care because the available resources have become inadequate to meet the needs of all patients. Recommendation 5-3: Global (World Health Organization) and re- gional (e.g., African Centres for Disease Control and Prevention, Euro- pean Centre for Disease Prevention and Control, Pan American Health Organization) health organizations should collaborate to determine how therapeutics and the resources needed for their delivery can be shared among countries to ensure equitable distribution and reduce or slow the spread of the pandemic. Recommendation 5-4: Intergovernmental organizations, government agencies, foundations, pharmaceutical and biotechnology companies, universities, and research institutes should focus their efforts on re- PREPUBLICATION COPY—Uncorrected Proofs

10 NON-VACCINE INFLUENZA INTERVENTIONS search strategies and platforms that were shown to be particularly effective during the COVID-19 pandemic: screening potential antiviral drugs for safety and efficacy; evaluating therapeutic approaches that target host responses in addition to the viruses themselves; developing and maintaining national and international research collaboratives; and building the capacity for rapid adaptive therapeutic evaluation during a pandemic to inform evidence-based treatment guidelines. This study advocates for policy makers and other stakeholders to give concerted attention to non-vaccine control measures for seasonal and pandemic respiratory viruses. Although many prominent research agen- das and initiatives for respiratory viruses focus on vaccines, non-vaccine interventions are the first line of defense for mitigating transmission. This is obviously true before a vaccine exists. However, as an outbreak or pan- demic evolves and vaccines are developed, such interventions continue to be simple, cost-effective countermeasures, which makes them an essential part of any effort to end an outbreak, since vaccines are neither completely effective nor immediately available to everyone at risk. Furthermore, when infections do occur, therapeutics are the last line of defense to avert the ef- fects. Therefore, research to develop and test non-vaccine control measures should be a priority, particularly in low- and middle-income country set- tings, to enable governments to best leverage such measures during respira- tory virus events. The next novel influenza or other respiratory pathogen posing a severe threat to human health is a matter of when and where, not if. Strategic prioritization of non-vaccine control measures at the global, regional, and local levels is needed now. REFERENCES Brownstein, J. S., K. P. Kleinman, and K. D. Mandl. 2005. Identifying pediatric age groups for influenza vaccination using a real-time regional surveillance system. American Journal of Epidemiology 162(7):686–693. https://doi.org/10.1093/aje/kwi257. Karlsson, E. A., P. A. N. Mook, K. Vandemaele, J. Fitzner, A. Hammond, V. Cozza, W. Zhang, and A. Moen. 2021. Review of global influenza circulation, late 2019 to 2020, and the impact of the COVID-19 pandemic on influenza circulation. Weekly Epidemiological Record (5)96:241–264. https://www.who.int/publications/i/item/who-wer-9625-241-26. Madhav, N., B. Oppenheim, M. Gallivan, P. Mulembakani, E. Rubin, and N. Wolfe. 2017. Chapter 17: Pandemics: Risks, impacts, and mitigation in disease control priorities: Improving health and reducing poverty. Washington, DC: International Bank for Re- construction and Development. Stojanovic, J., V. G. Boucher, J. Boyle, J. Enticott, K. L. Lavoie, and S. L. Bacon. 2021. COVID-19 is not the flu: Four graphs from four countries. Frontiers in Public Health 9:628479. WHO (World Health Organization). 2021. Weekly epidemiological update on COVID-19—18 May 2021. https://www.who.int/publications/m/item/weekly-epidemiological-update-on- covid-19---18-may-2021 (accessed May 21, 2021). PREPUBLICATION COPY—Uncorrected Proofs

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The COVID-19 pandemic has challenged the world's preparedness for a respiratory virus event. While the world has been combating COVID-19, seasonal and pandemic influenza remain imminent global health threats. Non-vaccine public health control measures can combat emerging and ongoing influenza outbreaks by mitigating viral spread.

Public Health Lessons for Non-Vaccine Influenza Interventions examines provides conclusions and recommendations from an expert committee on how to leverage the knowledge gained from the COVID-19 pandemic to optimize the use of public health interventions other than vaccines to decrease the toll of future seasonal and potentially pandemic influenza. It considers the effectiveness of public health efforts such as use of masks and indoor spacing, use of treatments such as monoclonal antibodies, and public health communication campaigns.

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