Introduction: The COVID-19 pandemic continues with highly contagious variants and waning immunity. As the virus keeps evolving to be more infectious and immune evasive, some question whether the COVID-19 pandemic can be managed through sustainable public health measures.

Methods: We developed an agent-based simulation to explore the impact of COVID-19 mutations, periodic vaccinations, and nonpharmaceutical interventions on reducing COVID-19 deaths. The model is calibrated to the greater Seattle area by observing local epidemic data. We perform scenario analyses on viral mutations that change infectiousness, disease severity, and immune evasiveness from previous infections and vaccination every 6 months. The simulation is run until the end of year 2023.

Results: Variants with increased infectivity or increased immune evasion dominate previous strains. With enhanced immune protection from a pancoronavirus vaccine, the most optimistic periodic vaccination rate reduces average total deaths by 44.6% compared with the most pessimistic periodic vaccination rate. A strict threshold nonpharmaceutical intervention policy reduces average total deaths by 71.3% compared with an open society, whereas a moderate nonpharmaceutical intervention policy results in a 33.6% reduction.

Conclusions: 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733698PMC
http://dx.doi.org/10.1016/j.focus.2023.100155DOI Listing

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