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The objective is to understand the role of emerging variants, vaccination, and NPI policies on COVID-19 infections and deaths. We aim to identify scenarios in which COVID-19 can be managed such that the death rate from COVID-19 becomes comparable with the combined annual mortality rate from influenza and pneumonia. As a case study for a large urban area, we simulate COVID-19 transmission in King County, Washington, (greater Seattle) using an agent- based simulation model. Calibrated to local epidemiological data, our study uses detailed synthetic population data and includes interactions between vaccination and specific NPIs while considering waning immunity and emergence of variants. Virus mutation scenarios include 12 combinations of infectivity, disease severity, and immune evasiveness. A highly effective pancoronavirus vaccine that works against all strains is considered an optimistic scenario. Our findings highlight the potential benefits of pancoronavirus vaccines that offer enhanced and longer-lasting immunity. We emphasize the crucial role of nonpharmaceutical interventions in reducing COVID-19 deaths regardless of virus mutation scenarios. Owing to highly immune evasive and contagious SARS-CoV-2 variants, most scenarios in this study fail to reduce the mortality of COVID-19 to the level of influenza and pneumonia. However, our findings indicate that periodic vaccinations and a threshold nonpharmaceutical intervention policy may succeed in achieving this goal. This indicates the need for caution and vigilance in managing a continuing COVID-19 epidemic. 

Calibration is a crucial step for model validity, yet its representation is often disregarded. This paper proposes a two-stage approach to calibrate a model that represents target data by identifying multiple diverse parameter sets while remaining computationally efficient. The first stage employs a black-box optimization algorithm to generate near-optimal parameter sets, the second stage clusters the generated parameter sets. Five black-box optimization algorithms, namely, Latin Hypercube Sampling (LHS), Sequential Model-based Algorithm Configuration (SMAC), Optuna, Simulated Annealing (SA), and Genetic Algorithm (GA), are tested and compared using a disease-opinion compartmental model with predicted health outcomes. Results show that LHS and Optuna allow more exploration and capture more variety in possible future health outcomes. SMAC, SA, and GA, are better at finding the best parameter set but their sampling approach generates less diverse model outcomes. This two-stage approach can reduce computation time while producing robust and representative calibration. 

The outbreak of seasonal flu costs billions of dollars in health care utilization and lost productivity. Despite the effectiveness of vaccination and antiviral medications to prevent serious flu-related complications and slow down the spread of an influenza epidemic, only 52% of the U.S. population aged 6 months and older received flu vaccines in the 2019-20 flu season. In addition, a costly out-of-pocket expense results in fewer patients seeking treatment, leading to potential hospitalizations and even flu-related deaths. In this study, we develop an integrated healthcare insurance mechanism that optimizes two incentive policies, vaccination reward and cost-sharing, to alleviate the medical cost and disease burden while preventing the outbreak of seasonal influenza. We model the dynamic interaction between a single insurer and multiple insureds as a Stackelberg vaccination game; we then embed the game into an agent-based simulation to model the spread of flu in a population under different policies. Finally, we apply machine learning and simulation optimization to optimize healthcare incentive policies in a large-scale flu transmission simulation. Simulation results indicate that the proposed methodology efficiently identifies a set of good incentive policies under different scenarios of flu vaccine efficacy and reproduction numbers. 

As the novel coronavirus (COVID-19) pandemic continues to expand, policymakers are striving to balance the combinations of nonpharmaceutical interventions (NPIs) to keep people safe and minimize social disruptions. We developed and calibrated an agent-based simulation to model COVID-19 outbreaks in the greater Seattle area. The model simulated NPIs, including social distancing, face mask use, school closure, testing, and contact tracing with variable compliance and effectiveness to identify optimal NPI combinations that can control the spread of the virus in a large urban area. Results highlight the importance of at least 75% face mask use to relax social distancing and school closure measures while keeping infections low. It is important to relax NPIs cautiously during vaccine rollout in 2021.