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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.