Scenario design for infectious disease projections: Integrating concepts from decision analysis and experimental design.

Across many fields, scenario modeling has become an important tool for exploring long-term projections and how they might depend on potential interventions and critical uncertainties, with relevance to both decision makers and scientists. In the past decade, and especially during the COVID-19 pandemic, the field of epidemiology has seen substantial growth in the use of scenario projections. Multiple scenarios are often projected at the same time, allowing important comparisons that can guide the choice of intervention, the prioritization of research topics, or public communication. The design of the scenarios is central to their ability to inform important questions. In this paper, we draw on the fields of decision analysis and statistical design of experiments to propose a framework for scenario design in epidemiology, with relevance also to other fields. We identify six different fundamental purposes for scenario designs (decision making, sensitivity analysis, situational awareness, horizon scanning, forecasting, and value of information) and discuss how those purposes guide the structure of scenarios. We discuss other aspects of the content and process of scenario design, broadly for all settings and specifically for multi-model ensemble projections. As an illustrative case study, we examine the first 17 rounds of scenarios from the U.S. COVID-19 Scenario Modeling Hub, then reflect on future advancements that could improve the design of scenarios in epidemiological settings.

Novel multi-cluster workflow system to support real-time HPC-enabled epidemic science: Investigating the impact of vaccine acceptance on COVID-19 spread.

We present MacKenzie, a HPC-driven multi-cluster workflow system that was used repeatedly to configure and execute fine-grained US national-scale epidemic simulation models during the COVID-19 pandemic. Mackenzie supported federal and Virginia policymakers, in real-time, for a large number of "what-if" scenarios during the COVID-19 pandemic, and continues to be used to answer related questions as COVID-19 transitions to the endemic stage of the disease. MacKenzie is a novel HPC meta-scheduler that can execute US-scale simulation models and associated workflows that typically present significant big data challenges. The meta-scheduler optimizes the total execution time of simulations in the workflow, and helps improve overall human productivity. As an exemplar of the kind of studies that can be conducted using Mackenzie, we present a modeling study to understand the impact of vaccine-acceptance in controlling the spread of COVID-19 in the US. We use a 288 million node synthetic social contact network (digital twin) spanning all 50 US states plus Washington DC, comprised of 3300 counties, with 12 billion daily interactions. The highly-resolved agent-based model used for the epidemic simulations uses realistic information about disease progression, vaccine uptake, production schedules, acceptance trends, prevalence, and social distancing guidelines. Computational experiments show that, for the simulation workload discussed above, MacKenzie is able to scale up well to 10K CPU cores. Our modeling results show that, when compared to faster and accelerating vaccinations, slower vaccination rates due to vaccine hesitancy cause averted infections to drop from 6.7M to 4.5M, and averted total deaths to drop from 39.4K to 28.2K across the US. This occurs despite the fact that the final vaccine coverage is the same in both scenarios. We also find that if vaccine acceptance could be increased by 10% in all states, averted infections could be increased from 4.5M to 4.7M (a 4.4% improvement) and total averted deaths could be increased from 28.2K to 29.9K (a 6% improvement) nationwide.

Wastewater-based Epidemiology for COVID-19 Surveillance: A Survey.

The pandemic of COVID-19 has imposed tremendous pressure on public health systems and social economic ecosystems over the past years. To alleviate its social impact, it is important to proactively track the prevalence of COVID-19 within communities. The traditional way to estimate the disease prevalence is to estimate from reported clinical test data or surveys. However, the coverage of clinical tests is often limited and the tests can be labor-intensive, requires reliable and timely results, and consistent diagnostic and reporting criteria. Recent studies revealed that patients who are diagnosed with COVID-19 often undergo fecal shedding of SARS-CoV-2 virus into wastewater, which makes wastewater-based epidemiology (WBE) for COVID-19 surveillance a promising approach to complement traditional clinical testing. In this paper, we survey the existing literature regarding WBE for COVID-19 surveillance and summarize the current advances in the area. Specifically, we have covered the key aspects of wastewater sampling, sample testing, and presented a comprehensive and organized summary of wastewater data analytical methods. Finally, we provide the open challenges on current wastewater-based COVID-19 surveillance studies, aiming to encourage new ideas to advance the development of effective wastewater-based surveillance systems for general infectious diseases.

An agent-based framework to study forced migration: A case study of Ukraine.

The ongoing Russian aggression against Ukraine has forced over eight million people to migrate out of Ukraine. Understanding the dynamics of forced migration is essential for policy-making and for delivering humanitarian assistance. Existing work is hindered by a reliance on observational data which is only available well after the fact. In this work, we study the efficacy of a data-driven agent-based framework motivated by social and behavioral theory in predicting outflow of migrants as a result of conflict events during the initial phase of the Ukraine war. We discuss policy use cases for the proposed framework by demonstrating how it can leverage refugee demographic details to answer pressing policy questions. We also show how to incorporate conflict forecast scenarios to predict future conflict-induced migration flows. Detailed future migration estimates across various conflict scenarios can both help to reduce policymaker uncertainty and improve allocation and staging of limited humanitarian resources in crisis settings.

Data-driven mechanistic framework with stratified immunity and effective transmissibility for COVID-19 scenario projections.

Scenario-based modeling frameworks have been widely used to support policy-making at state and federal levels in the United States during the COVID-19 response. While custom-built models can be used to support one-off studies, sustained updates to projections under changing pandemic conditions requires a robust, integrated, and adaptive framework. In this paper, we describe one such framework, UVA-adaptive, that was built to support the CDC-aligned Scenario Modeling Hub (SMH) across multiple rounds, as well as weekly/biweekly projections to Virginia Department of Health (VDH) and US Department of Defense during the COVID-19 response. Building upon an existing metapopulation framework, PatchSim, UVA-adaptive uses a calibration mechanism relying on adjustable effective transmissibility as a basis for scenario definition while also incorporating real-time datasets on case incidence, seroprevalence, variant characteristics, and vaccine uptake. Through the pandemic, our framework evolved by incorporating available data sources and was extended to capture complexities of multiple strains and heterogeneous immunity of the population. Here we present the version of the model that was used for the recent projections for SMH and VDH, describe the calibration and projection framework, and demonstrate that the calibrated transmissibility correlates with the evolution of the pathogen as well as associated societal dynamics.

A simplicial epidemic model for COVID-19 spread analysis.

Networks allow us to describe a wide range of interaction phenomena that occur in complex systems arising in such diverse fields of knowledge as neuroscience, engineering, ecology, finance, and social sciences. Until very recently, the primary focus of network models and tools has been on describing the pairwise relationships between system entities. However, increasingly more studies indicate that polyadic or higher-order group relationships among multiple network entities may be the key toward better understanding of the intrinsic mechanisms behind the functionality of complex systems. Such group interactions can be, in turn, described in a holistic manner by simplicial complexes of graphs. Inspired by these recently emerging results on the utility of the simplicial geometry of complex networks for contagion propagation and armed with a large-scale synthetic social contact network (also known as a digital twin) of the population in the U.S. state of Virginia, in this paper, we aim to glean insights into the role of higher-order social interactions and the associated varying social group determinants on COVID-19 propagation and mitigation measures.

Coupled models of genomic surveillance and evolving pandemics with applications for timely public health interventions.

Disease surveillance systems provide early warnings of disease outbreaks before they become public health emergencies. However, pandemics containment would be challenging due to the complex immunity landscape created by multiple variants. Genomic surveillance is critical for detecting novel variants with diverse characteristics and importation/emergence times. Yet, a systematic study incorporating genomic monitoring, situation assessment, and intervention strategies is lacking in the literature. We formulate an integrated computational modeling framework to study a realistic course of action based on sequencing, analysis, and response. We study the effects of the second variant's importation time, its infectiousness advantage and, its cross-infection on the novel variant's detection time, and the resulting intervention scenarios to contain epidemics driven by two-variants dynamics. Our results illustrate the limitation in the intervention's effectiveness due to the variants' competing dynamics and provide the following insights: i) There is a set of importation times that yields the worst detection time for the second variant, which depends on the first variant's basic reproductive number; ii) When the second variant is imported relatively early with respect to the first variant, the cross-infection level does not impact the detection time of the second variant. We found that depending on the target metric, the best outcomes are attained under different interventions' regimes. Our results emphasize the importance of sustained enforcement of Non-Pharmaceutical Interventions on preventing epidemic resurgence due to importation/emergence of novel variants. We also discuss how our methods can be used to study when a novel variant emerges within a population.

Scenario Design for Infectious Disease Projections: Integrating Concepts from Decision Analysis and Experimental Design.

Across many fields, scenario modeling has become an important tool for exploring long-term projections and how they might depend on potential interventions and critical uncertainties, with relevance to both decision makers and scientists. In the past decade, and especially during the COVID-19 pandemic, the field of epidemiology has seen substantial growth in the use of scenario projections. Multiple scenarios are often projected at the same time, allowing important comparisons that can guide the choice of intervention, the prioritization of research topics, or public communication. The design of the scenarios is central to their ability to inform important questions. In this paper, we draw on the fields of decision analysis and statistical design of experiments to propose a framework for scenario design in epidemiology, with relevance also to other fields. We identify six different fundamental purposes for scenario designs (decision making, sensitivity analysis, value of information, situational awareness, horizon scanning, and forecasting) and discuss how those purposes guide the structure of scenarios. We discuss other aspects of the content and process of scenario design, broadly for all settings and specifically for multi-model ensemble projections. As an illustrative case study, we examine the first 17 rounds of scenarios from the U.S. COVID-19 Scenario Modeling Hub, then reflect on future advancements that could improve the design of scenarios in epidemiological settings.

A synthetic population of Sweden: datasets of agents, households, and activity-travel patterns.

A synthetic population is a simplified microscopic representation of an actual population. Statistically representative at the population level, it provides valuable inputs to simulation models (especially agent-based models) in research areas such as transportation, land use, economics, and epidemiology. This article describes the datasets from the Synthetic Sweden Mobility (SySMo) model using the state-of-art methodology, including machine learning (ML), iterative proportional fitting (IPF), and probabilistic sampling. The model provides a synthetic replica of over 10 million Swedish individuals (i.e., agents), their household characteristics, and activity-travel plans. This paper briefly explains the methodology for the three datasets: Person, Households, and Activity-travel patterns. Each agent contains socio-demographic attributes, such as age, gender, civil status, residential zone, personal income, car ownership, employment, etc. Each agent also has a household and corresponding attributes such as household size, number of children ≤ 6 years old, etc. These characteristics are the basis for the agents' daily activity-travel schedule, including type of activity, start-end time, duration, sequence, the location of each activity, and the travel mode between activities.

Airborne disease transmission during indoor gatherings over multiple time scales: Modeling framework and policy implications.

Indoor superspreading events are significant drivers of transmission of respiratory diseases. In this work, we study the dynamics of airborne transmission in consecutive meetings of individuals in enclosed spaces. In contrast to the usual pairwise-interaction models of infection where effective contacts transmit the disease, we focus on group interactions where individuals with distinct health states meet simultaneously. Specifically, the disease is transmitted by infected individuals exhaling droplets (contributing to the viral load in the closed space) and susceptible ones inhaling the contaminated air. We propose a modeling framework that couples the fast dynamics of the viral load attained over meetings in enclosed spaces and the slow dynamics of disease progression at the population level. Our modeling framework incorporates the multiple time scales involved in different setups in which indoor events may happen, from single-time events to events hosting multiple meetings per day, over many days. We present theoretical and numerical results of trade-offs between the room characteristics (ventilation system efficiency and air mass) and the group's behavioral and composition characteristics (group size, mask compliance, testing, meeting time, and break times), that inform indoor policies to achieve disease control in closed environments through different pathways. Our results emphasize the impact of break times, mask-wearing, and testing on facilitating the conditions to achieve disease control. We study scenarios of different break times, mask compliance, and testing. We also derive policy guidelines to contain the infection rate under a certain threshold.

COVID-19 non-pharmaceutical interventions: data annotation for rapidly changing local policy information.

Understanding the scope, prevalence, and impact of the COVID-19 pandemic response will be a rich ground for research for many years. Key to the response to COVID-19 was the non-pharmaceutical intervention (NPI) measures, such as mask mandates or stay-in-place orders. For future pandemic preparedness, it is critical to understand the impact and scope of these interventions. Given the ongoing nature of the pandemic, existing NPI studies covering only the initial portion provide only a narrow view of the impact of NPI measures. This paper describes a dataset of NPI measures taken by counties in the U.S. state of Virginia that include measures taken over the first two years of the pandemic beginning in March 2020. This data enables analyses of NPI measures over a long time period that can produce impact analyses on both the individual NPI effectiveness in slowing the pandemic spread, and the impact of various NPI measures on the behavior and conditions of the different counties and state.

High resolution synthetic residential energy use profiles for the United States.

Efficient energy consumption is crucial for achieving sustainable energy goals in the era of climate change and grid modernization. Thus, it is vital to understand how energy is consumed at finer resolutions such as household in order to plan demand-response events or analyze impacts of weather, electricity prices, electric vehicles, solar, and occupancy schedules on energy consumption. However, availability and access to detailed energy-use data, which would enable detailed studies, has been rare. In this paper, we release a unique, large-scale, digital-twin of residential energy-use dataset for the residential sector across the contiguous United States covering millions of households. The data comprise of hourly energy use profiles for synthetic households, disaggregated into Thermostatically Controlled Loads (TCL) and appliance use. The underlying framework is constructed using a bottom-up approach. Diverse open-source surveys and first principles models are used for end-use modeling. Extensive validation of the synthetic dataset has been conducted through comparisons with reported energy-use data. We present a detailed, open, high resolution, residential energy-use dataset for the United States.

Disease burden among Ukrainians forcibly displaced by the 2022 Russian invasion.

The Russian invasion of Ukraine on February 24, 2022, has displaced more than a quarter of the population. Assessing disease burdens among displaced people is instrumental in informing global public health and humanitarian aid efforts. We estimated the disease burden in Ukrainians displaced both within Ukraine and to other countries by combining a spatiotemporal model of forcible displacement with age- and gender-specific estimates of cardiovascular disease (CVD), diabetes, cancer, HIV, and tuberculosis (TB) in each of Ukraine's 629 raions (i.e., districts). Among displaced Ukrainians as of May 13, we estimated that more than 2.63 million have CVDs, at least 615,000 have diabetes, and over 98,500 have cancer. In addition, more than 86,000 forcibly displaced individuals are living with HIV, and approximately 13,500 have TB. We estimated that the disease prevalence among refugees was lower than the national disease prevalence before the invasion. Accounting for internal displacement and healthcare facilities impacted by the conflict, we estimated that the number of people per hospital has increased by more than two-fold in some areas. As regional healthcare systems come under increasing strain, these estimates can inform the allocation of critical resources under shifting disease burdens.

Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: A multi-model study.

Background: The COVID-19 Scenario Modeling Hub convened nine modeling teams to project the impact of expanding SARS-CoV-2 vaccination to children aged 5-11 years on COVID-19 burden and resilience against variant strains. Methods: Teams contributed state- and national-level weekly projections of cases, hospitalizations, and deaths in the United States from September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of 1) vaccination (or not) of children aged 5-11 years (starting November 1, 2021), and 2) emergence (or not) of a variant more transmissible than the Delta variant (emerging November 15, 2021). Individual team projections were linearly pooled. The effect of childhood vaccination on overall and age-specific outcomes was estimated using meta-analyses. Findings: Assuming that a new variant would not emerge, all-age COVID-19 outcomes were projected to decrease nationally through mid-March 2022. In this setting, vaccination of children 5-11 years old was associated with reductions in projections for all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios without childhood vaccination. Vaccine benefits increased for scenarios including a hypothesized more transmissible variant, assuming similar vaccine effectiveness. Projected relative reductions in cumulative outcomes were larger for children than for the entire population. State-level variation was observed. Interpretation: Given the scenario assumptions (defined before the emergence of Omicron), expanding vaccination to children 5-11 years old would provide measurable direct benefits, as well as indirect benefits to the all-age U.S. population, including resilience to more transmissible variants. Funding: Various (see acknowledgments).

Data-driven scalable pipeline using national agent-based models for real-time pandemic response and decision support.

This paper describes an integrated, data-driven operational pipeline based on national agent-based models to support federal and state-level pandemic planning and response. The pipeline consists of (i) an automatic semantic-aware scheduling method that coordinates jobs across two separate high performance computing systems; (ii) a data pipeline to collect, integrate and organize national and county-level disaggregated data for initialization and post-simulation analysis; (iii) a digital twin of national social contact networks made up of 288 Million individuals and 12.6 Billion time-varying interactions covering the US states and DC; (iv) an extension of a parallel agent-based simulation model to study epidemic dynamics and associated interventions. This pipeline can run 400 replicates of national runs in less than 33 h, and reduces the need for human intervention, resulting in faster turnaround times and higher reliability and accuracy of the results. Scientifically, the work has led to significant advances in real-time epidemic sciences.

Ensembles of realistic power distribution networks.

The power grid is going through significant changes with the introduction of renewable energy sources and the incorporation of smart grid technologies. These rapid advancements necessitate new models and analyses to keep up with the various emergent phenomena they induce. A major prerequisite of such work is the acquisition of well-constructed and accurate network datasets for the power grid infrastructure. In this paper, we propose a robust, scalable framework to synthesize power distribution networks that resemble their physical counterparts for a given region. We use openly available information about interdependent road and building infrastructures to construct the networks. In contrast to prior work based on network statistics, we incorporate engineering and economic constraints to create the networks. Additionally, we provide a framework to create ensembles of power distribution networks to generate multiple possible instances of the network for a given region. The comprehensive dataset consists of nodes with attributes, such as geocoordinates; type of node (residence, transformer, or substation); and edges with attributes, such as geometry, type of line (feeder lines, primary or secondary), and line parameters. For validation, we provide detailed comparisons of the generated networks with actual distribution networks. The generated datasets represent realistic test systems (as compared with standard test cases published by Institute of Electrical and Electronics Engineers (IEEE)) that can be used by network scientists to analyze complex events in power grids and to perform detailed sensitivity and statistical analyses over ensembles of networks.

Heterogeneous adaptive behavioral responses may increase epidemic burden.

Non-pharmaceutical interventions (NPIs) constitute the front-line responses against epidemics. Yet, the interdependence of control measures and individual microeconomics, beliefs, perceptions and health incentives, is not well understood. Epidemics constitute complex adaptive systems where individual behavioral decisions drive and are driven by, among other things, the risk of infection. To study the impact of heterogeneous behavioral responses on the epidemic burden, we formulate a two risk-groups mathematical model that incorporates individual behavioral decisions driven by risk perceptions. Our results show a trade-off between the efforts to avoid infection by the risk-evader population, and the proportion of risk-taker individuals with relaxed infection risk perceptions. We show that, in a structured population, privately computed optimal behavioral responses may lead to an increase in the final size of the epidemic, when compared to the homogeneous behavior scenario. Moreover, we find that uncertain information on the individuals' true health state may lead to worse epidemic outcomes, ultimately depending on the population's risk-group composition. Finally, we find there is a set of specific optimal planning horizons minimizing the final epidemic size, which depend on the population structure.

Understanding the coevolution of mask wearing and epidemics: A network perspective.

Nonpharmaceutical interventions (NPIs) such as mask wearing can be effective in mitigating the spread of infectious diseases. Therefore, understanding the behavioral dynamics of NPIs is critical for characterizing the dynamics of disease spread. Nevertheless, standard infection models tend to focus only on disease states, overlooking the dynamics of "beneficial contagions," e.g., compliance with NPIs. In this work, we investigate the concurrent spread of disease and mask-wearing behavior over multiplex networks. Our proposed framework captures both the competing and complementary relationships between the dueling contagion processes. Further, the model accounts for various behavioral mechanisms that influence mask wearing, such as peer pressure and fear of infection. Our results reveal that under the coupled disease-behavior dynamics, the attack rate of a disease-as a function of transition probability-exhibits a critical transition. Specifically, as the transmission probability exceeds a critical threshold, the attack rate decreases abruptly due to sustained mask-wearing responses. We empirically explore the causes of the critical transition and demonstrate the robustness of the observed phenomena. Our results highlight that without proper enforcement of NPIs, reductions in the disease transmission probability via other interventions may not be sufficient to reduce the final epidemic size.

Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination.

In Spring 2021, the highly transmissible SARS-CoV-2 Delta variant began to cause increases in cases, hospitalizations, and deaths in parts of the United States. At the time, with slowed vaccination uptake, this novel variant was expected to increase the risk of pandemic resurgence in the US in summer and fall 2021. As part of the COVID-19 Scenario Modeling Hub, an ensemble of nine mechanistic models produced 6-month scenario projections for July-December 2021 for the United States. These projections estimated substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant, projected to occur across most of the US, coinciding with school and business reopening. The scenarios revealed that reaching higher vaccine coverage in July-December 2021 reduced the size and duration of the projected resurgence substantially, with the expected impacts was largely concentrated in a subset of states with lower vaccination coverage. Despite accurate projection of COVID-19 surges occurring and timing, the magnitude was substantially underestimated 2021 by the models compared with the of the reported cases, hospitalizations, and deaths occurring during July-December, highlighting the continued challenges to predict the evolving COVID-19 pandemic. Vaccination uptake remains critical to limiting transmission and disease, particularly in states with lower vaccination coverage. Higher vaccination goals at the onset of the surge of the new variant were estimated to avert over 1.5 million cases and 21,000 deaths, although may have had even greater impacts, considering the underestimated resurgence magnitude from the model.

Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: a multi-model study.

Background: SARS-CoV-2 vaccination of persons aged 12 years and older has reduced disease burden in the United States. The COVID-19 Scenario Modeling Hub convened multiple modeling teams in September 2021 to project the impact of expanding vaccine administration to children 5-11 years old on anticipated COVID-19 burden and resilience against variant strains. Methods: Nine modeling teams contributed state- and national-level projections for weekly counts of cases, hospitalizations, and deaths in the United States for the period September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of: 1) presence vs. absence of vaccination of children ages 5-11 years starting on November 1, 2021; and 2) continued dominance of the Delta variant vs. emergence of a hypothetical more transmissible variant on November 15, 2021. Individual team projections were combined using linear pooling. The effect of childhood vaccination on overall and age-specific outcomes was estimated by meta-analysis approaches. Findings: Absent a new variant, COVID-19 cases, hospitalizations, and deaths among all ages were projected to decrease nationally through mid-March 2022. Under a set of specific assumptions, models projected that vaccination of children 5-11 years old was associated with reductions in all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios where children were not vaccinated. This projected effect of vaccinating children 5-11 years old increased in the presence of a more transmissible variant, assuming no change in vaccine effectiveness by variant. Larger relative reductions in cumulative cases, hospitalizations, and deaths were observed for children than for the entire U.S. population. Substantial state-level variation was projected in epidemic trajectories, vaccine benefits, and variant impacts. Conclusions: Results from this multi-model aggregation study suggest that, under a specific set of scenario assumptions, expanding vaccination to children 5-11 years old would provide measurable direct benefits to this age group and indirect benefits to the all-age U.S. population, including resilience to more transmissible variants.