Effective Pandemic Response: Linking Evidence, Intervention, Politics, Organization, and Governance

The following sections are included:

• Preface Effective Pandemic Response: Linking Evidence, Intervention, Politics, Organization, and Governance A World Scientific Reference on Pandemics
• Preface to Volume 1
• About the Editor-in-Chief
• About the Editors
• About the Contributors and Series Editors
• Acknowledgments
• Contents

The COVID-19 pandemic is described by many people as an unprecedented event. Since its emergence in late 2019, SARS CoV-2 has spread around the world, caused millions of global deaths, reduced life expectancy, and caused widespread economic disruption and social upheaval. While most people alive today have never experienced a pandemic on this scale, these occurrences have been regular, if not predictable, throughout human history. Many have caused far greater relative mortality than what we experienced with COVID-19, and have changed the course of societies and civilizations [1]. While SARS CoV-2 is a dangerous pathogen, it has produced nowhere near the case-fatality rates of historic pandemics, such as bubonic plague. Moreover, we currently enjoy the benefit of applying germ theory, public health measures, microbial genomics, and immunization — the application of which has had huge potential to reduce spread and morbidity; however, factors beyond science have led to unequal benefits from these advances…

The following sections are included:

• A comprehensive understanding of SARS-CoV-2 transmission and the biological underpinnings of COVID-19 is essential for public health professionals and clinicians to adequately implement intervention and control measures.
• Novel SARS-CoV-2 variants continue to emerge, displaying increased transmissibility associated with changes in the virus’s antigenic profile. Infection with Omicron subvariants is associated with a lower risk of developing severe COVID-19 which may reflect a combination of evolving virulence and the impact of population-level immunity from vaccine and/or infection which typically reduces infection severity; increased transmissibility appears to result in more widespread transmission which as a consequence can result in more individuals being infected, and this would be expected to lead to increased rates of hospitalization especially in those with co-morbid illnesses, or those lacking vaccine/infection or hybrid immunity. Continued genomic sequencing and mutational analysis can offer critical insights into vaccine/infection and hybrid immunity and help understand the incremental impact of antivirals.
• Attachment of SARS-CoV-2 to the host ACE2 receptor occurs via the S1 subunit of the spike protein contained within the viral envelope. Subsequently, host cell entry can occur via the cell surface or endosomal route. Preference for either route can influence viral tropism in the upper or lower respiratory tract and thereby influence the transmissibility and severity of COVID-19.
• Transmission of SARS-CoV-2 occurs primarily through respiratory droplets and aerosols. Other possible modes of transmission include direct contact with bodily fluids. There is limited data on the importance and contribution of fecal–oral transmission, and transplacental transmission.
• Several factors, such as biological sex, the presence of multiple comorbidities, and age, have consistently been correlated with increased COVID-19 severity and worsened prognosis. Involvement of the lower respiratory tract, including pneumonia and acute respiratory distress syndrome, may necessitate ICU admission and direct intervention by mechanical ventilation. However, just as the virus is evolving genotypically and phenotypically, vaccination/infection and hybrid immunity have dramatically lowered the impact of infection on morbidity and mortality.
• Post-acute sequelae of COVID-19 (PASC) or long COVID, presents with highly variable symptoms and has been associated with some neurological and neuropsychiatric manifestations. Because of the heterogeneity in defining PASC, it has been difficult to precisely quantify the proportion of infected individuals who develop PASC. Vaccination and/or prior infection and hybrid immunity appear to diminish the risk of PASC, and as a result, it is difficult to tease apart the relative risks of specific variants, e.g., Delta vs. Omicron on developing PASC. This is because the variant waves occurred in populations that had very different levels of vaccine, infection, and/or hybrid immunity.

The following sections are included:

• The primary receptor for SARS-CoV-2 is the angiotensin-converting enzyme 2 (ACE2) receptor; however, other receptors such as CD147 and neuropilin-1 (NRP-1) may be involved in the viral entry facilitation.
• The host immune system is designed to defend the body against infection and disease, but like other viral pathogens, SARS-CoV-2 has developed unique mechanisms to evade these immune defenses and infect the host. In some cases, the overactivation of the immune response driven by both host and viral factors can increase disease severity.
• Newer variants of SARS-CoV-2 have evolved to enter host cells and evade the immune system through mutations in their receptor binding domains as well as other mutations which improve replication efficiency. These mutations can increase the amount of virus produced and shed, which can impact transmissibility. Other mutations can impact viral virulence affecting host pathogenicity.
• Many host factors may affect COVID-19 pathogenesis, including age, biological sex, comorbidities, and immunity from vaccination and/or infection. Additionally, viral entry and disease progression in the host may be influenced by changes in the virus which affect the affinity for host receptors and the ability to evade early or later immune system responses.
• COVID-19 infection can also have many potential short and long-term impacts that continue to evolve. For example, Multisystem Inflammatory Syndrome in Children (MIS-C) and Adults (MIS-A) and Long COVID appear to be less common in those vaccinated/previously infected. The underlying mechanisms behind these conditions remain uncertain with several hypotheses, such as acute organ damage and immune system dysfunction, being explored.

The following sections are included:

• SARS-CoV-2 likely originated from a zoonotic reservoir. Upon entry into human populations, it spread rapidly largely through the respiratory route.
• Asymptomatic transmission may occur early in SARS-CoV-2 infection and contribute both to the risk of pandemic growth and to the relative impact of public health interventions intended to curb spread.
• The speed of pandemic growth is determined by the reproduction number. For COVID-19, the risk of onward transmission from infected individuals was heterogeneous and widely dispersed, as evidenced by the importance of superspreading events.
• Transmission is impacted by host features and behaviors, as well as agent and environmental factors. Environmental factors such as temperature and ventilation place some venues at higher risk of transmission than others.
• Interest has gathered around the role of immunity from both prior infection and immunization, and its interplay with viral mutation in modifying disease transmission.
• Social determinants such as racism, discrimination, and poverty modify transmission risk at both individual and global levels, widening health inequities.
• Disease modeling can be used to predict features of the pandemic, and project outcomes under different scenarios. Modeling can help describe disease transmission and can inform public health interventions designed to interrupt transmission.

The following sections are included:

• Several diagnostic testing strategies for SARS-CoV-2, such as molecular tests and immunoassays, emerged over the course of the pandemic. Their development informed public health approaches to help control and contain the pandemic.
• Reverse transcription polymerase chain reaction (RT-PCR) stood as a forerunner early in the pandemic, but increasing case numbers and the emergence of new variants gradually overloaded the capacity for universal RT-PCR testing, calling for a re-evaluation and expansion of testing strategies.
• As the testing landscape shifted, point-of-care home-based antigen-detection strategies played an increasingly prominent role. While PCR remained the gold standard test, its applications were adapted to focus on targeted surveillance within at-risk populations, identification of new variants, and wastewater surveillance.
• While antibody detection through serology testing is not useful for the detection of acute SARS-CoV-2 infection, it plays an important role in the assessment of immunity and susceptibility at the population level. Serology testing also serves as a correlate of protection arising from prior infection or vaccination.
• Wastewater testing for SARS-CoV-2 viral particles can identify early warning signs of increasing transmission in the community, leading to a more proactive public health response and earlier outbreak detection.

The following sections are included:

• Public health surveillance is the ongoing, systematic collection, analysis, and interpretation of health data essential to the planning, implementation, and evaluation of public health practice, closely integrated with the timely dissemination of these data to those responsible for prevention and control [2].
• A variety of data streams for COVID-19 surveillance have been used throughout the pandemic, including laboratory testing, genomics, hospital, mortality, and wastewater data.
• The COVID-19 pandemic has highlighted challenges with scaling existing surveillance systems, specifically with respect to cross-jurisdictional collaboration, data quality and representativeness, and the timeliness of data reporting.
• In designing a surveillance system, it is crucial to incorporate the principles of an effective system within each step of data collection, analysis, interpretation, and dissemination, while also keeping system sustainability and resiliency in mind.

The following sections are included:

• Non-pharmaceutical interventions (NPIs) have been integral to the control of communicable diseases. They can be critical to outbreak control before pharmaceutical interventions are available and can be used to complement them once available. Screening, contact tracing, quarantine, isolation, and restrictions on travel are primary NPIs that have been adapted over the changing pandemic context.
• NPIs are implemented with the intention of lowering the reproduction number of communicable disease agents such as COVID-19 and are most effective in reducing viral transmission when implemented simultaneously. Additionally, the combined use of approaches to screening and contact tracing results in a more robust system to counteract the limitations of using either approach on its own.
• Each intervention has its own benefits, limitations, costs, and unintended consequences. Factors, such as the local context and the vulnerability of the population, must be considered for the timing, length, and extent of implementation.
• While these NPIs were crucial to curtailing the spread of COVID-19 in the context of low population immunity and limited availability of treatments, the current context of high population immunity, low disease severity, and healthcare systems able to keep up with demand requires more sustainable implementation approaches.
• As the pandemic transitions towards endemicity, policymakers must adapt implementation strategies for screening, contact tracing, isolation, quarantine, and travel restrictions. Decisions on maintaining, relaxing, or removing these measures should be based on evolving public health understanding and account for risks and the potential unintended consequences.

The following sections are included:

• Masks aim to both limit the release of pathogenic aerosols from infected individuals and protect those susceptible to exposure to these contents. Most research suggests that masks successfully reduce SARS-CoV-2 transmission; however, findings vary by mask type.
• Indoor air quality control includes ventilation and filtration measures that aim to remove or lower levels of virus-containing aerosols from an environment. Mechanical ventilation reduces the risk of SARS-CoV-2 infection and filtration can effectively clear pathogenic aerosols from a room.
• Physical distancing and physical barriers seek to prevent SARS-CoV-2-containing aerosols from reaching susceptible individuals. Physical distancing is consistently associated with a reduction in COVID-19 spread, while the success of physical barriers hinges upon design characteristics and co-located ventilation systems.
• Hand hygiene and surface disinfecting solutions aim to inactivate SARS-CoV-2 by attacking its lipid membrane; however, the primary airborne nature of transmission suggests limited utility of these interventions in this case.
• Most of the above interventions were emphasized in public advice and policies from early in the COVID-19 pandemic until spring 2022, with adaptations to preventive approaches ongoing in the current context.
• Moving forward, it is recommended that ventilation and filtration interventions for SARS-CoV-2 transmission be prioritized.

The following sections are included:

• COVID-19 Infection Prevention and Control (IPAC) measures in healthcare settings have evolved alongside our understanding of the virus, the burden of disease, and access to equipment and resources throughout the pandemic.
• IPAC measures can be categorized according to the established hierarchy of controls; layering measures from each level provides a coordinated response to substantially reduce the risk of SARS-CoV-2 transmission.
• In late 2021, the emergence of the Omicron variant changed the course of the pandemic as its high transmissibility significantly increased case counts, which quickly overwhelmed the healthcare system.
• While the majority of transmission occurred within the community, nosocomial transmission played a significant role in viral spread that resulted in multiple outbreaks in hospitals and long-term care settings worldwide. There is a multifaceted increase in the risk of nosocomial transmission in long-term care facilities compared to hospitals.
• Collaboration between safety teams — public health, occupational health, infection control partners, and clinical delivery partners — within acute and long-term care facilities is essential in the effective application of IPAC.
• Many lessons were learned about IPAC measures in healthcare settings throughout the pandemic and must be applied in preparation for future outbreaks and public health emergencies.

The following sections are included:

• The continuous growth in understanding of COVID-19 and its various clinical presentations has led to more targeted treatment approaches for different patient populations and severity levels.
• Some previously considered therapeutic options for COVID-19 treatment have been found to be less effective than once believed with potential side effects outweighing their benefits.
• In addition to the continued focus on symptom relief, antiviral medications are used to treat COVID-19 in non-hospitalized individuals at higher risk for severe illness.
• Understanding disease severity when establishing treatment strategies for hospitalized COVID-19 patients is fundamental for determining the most adequate therapeutic option to stabilize the patient and prevent disease progression.
• Post-acute sequelae of COVID-19 (PASC) refers to the persistence of symptoms beyond the acute phase of the illness, but much remains to be learned about effective therapeutic strategies to manage it.

The following sections are included:

• There are currently four designs being used for WHO-approved COVID-19 vaccines, which include whole inactivated, protein subunit, non-replicating viral vector, and mRNA.
• All vaccines elicit an immunogenic response following vaccination, including after booster dose, although comparisons across studies cannot be made due to a lack of international standardization.
• Passive and active post-marketing surveillance allows for continued monitoring of vaccine safety, effectiveness, and immunogenicity during and after a pandemic.
• Post-marketing surveillance has uncovered very rare adverse events that are often missed in clinical trials. These include myocarditis/pericarditis, thrombolytic clotting events, and Guillain–Barré syndrome.
• Overall vaccine effectiveness appears to decrease over time and with different COVID-19 variants circulating, highlighting the importance of ongoing clinical and molecular surveillance for infectious diseases.
• Platform-based technologies are likely to be the most rapid pathway to effective vaccines for future pathogenic threats.

The following sections are included:

• Population-based COVID-19 immunization is a complex and dynamic process due to limitations in vaccine supply, the differential impact of COVID-19 on populations, and the constant evolution of the virus and its variants.
• From 2020 through 2023, we have seen progress, with approximately 13.3 billion vaccine doses distributed and nearly 70% of the global population receiving at least one dose at the time of writing [1]. The processes applied in vaccination services, be it mass clinics in the USA or distributed approaches in India, have provided lessons to aid future preparedness.
• Vaccine uptake is driven by factors such as hesitancy, supply chain logistics, and inequitable distribution. Successful examples of combating these issues are discussed in this chapter.
• While studies show that COVID-19 vaccine-derived immunity wanes over time, the effectiveness of booster doses has been demonstrated in preventing serious outcomes including death.
• Immunization programming lessons learned from this pandemic must be applied to future pandemic planning for the globe.

The following sections are included:

• Risk communication is the exchange of real-time information, advice, and opinions with the goal of enabling people at risk to make informed decisions to protect their health, economic, or social well-being. Effective risk communication is an essential part of pandemic preparedness and response.
• Risk communication can help build and maintain public trust, especially in communicating scientific uncertainty and the deployment of the precautionary principle.
• During the COVID-19 pandemic, the WHO identified an “infodemic” — which arose due to a confluence of technology, social media, and the spread of misinformation, either unintentionally or deliberately (disinformation).
• Strategies to combat misinformation, disinformation, and conspiracy theories target both the individual level, by using debunking and tools for critical thinking, and the structural level, for example, by working with social media companies to combat spread.
• Conspiracy theories are often multilayered, nebulous, and resistant to disconfirmation. Strategies include addressing the political and psychological needs that give rise to conspiratorial thinking, helping individuals identify and evaluate information and prevent exposure of individuals to mis- and disinformation at a structural level.
• The 2022 Canadian Convoy Movement is a case study in risk communication that sheds light on distrust in government institutions, social media, mis- and disinformation, and conspiracy theories. It provides lessons for future risk communication in Canada and internationally.

The following sections are included:

• The Institutional, Politics, Organization and Governance (IPOG) framework speaks to some upstream determinants of the COVID-19 pandemic response and outlines the factors influencing decision-making processes.
• Both informal institutions (e.g., cultures, norms) and formal institutions (e.g., laws, policies) are aspects that greatly impact how a country responds to a pandemic and how societies comply with intervention.
• Government officials often had to manage varying competing interests to ensure effective governance, such as public health and the economy, while also considering their own personal ideologies and values.
• As vaccine nationalism and geopolitics took precedence, international organizations (e.g., WHO) and initiatives (e.g., COVAX) were unable to establish collaboration among high-income countries to meet global goals, such as vaccine equity.
• To achieve greater national and international accountability, recommendations point to a need for regulatory bodies and actors that are largely free from direct political interference and that have the authority to ensure vulnerable groups and countries are provided with the health responses needed.
• The key takeaway for public health is to grasp the overall societal conditions and context of a nation that inform decision-making.

The initial years of the COVID-19 pandemic are behind us and the toll to date has been objectively devastating. The World Health Organization [1] has confirmed seven million deaths, but as more go unreported, the full toll is estimated to be at least two or three times that number [1–3]. Social and economic disruption caused by the direct effects of the pandemic and by unintended consequences of control measures have been unprecedented, with the total cost to the United States economy alone estimated to be $14 trillion [4]. Today, we see global inflation being driven in part by pent-up consumer demand, accelerated egress from the labor pool, and an upward tick in wages. Yet things could have been much worse. A prevailing understanding of germ theory, rapid characterization of the pathogen, and deployment of public health measures and vaccines saved countless lives. While we are tempted to forget unpleasant times, there will be no true or permanent “post-pandemic world”; SARS CoV-2 continues to circulate, and a pandemic caused by another emerging pathogen is a complete certainty among eight billion humans. We only really have a breathing space between peak pandemic periods, and these spaces give us a chance to prepare — if we have the will, focus, and foresight to do so…

The following section is included:

• Index