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We introduce a policy model coupled with the susceptible–infected- recovered (SIR) epidemic model to study interactions between policy-making and the dynamics of epidemics. We considered both single-region policies as well as game-theoretic models involving interactions among several regions and hierarchical interactions among policy-makers modeled as multi-layer games. We assumed that the policy functions are piece-wise constant with a minimum time interval for each policy stage, considering that policies cannot change frequently in time or be easily followed. The optimal policy was obtained by minimizing a cost function that consists of an implementation cost, an impact cost, and, in the case of multi-layer games, a non-compliance cost. We show, in a case study of COVID-19 in France, that when the cost function is reduced to the impact cost and parameterized as the final epidemic size, the solution approximates that of the optimal control in Bliman et al, (2021) for a sufficiently small minimum policy time interval. For a larger time interval, however, the optimal policy is a step down function, quite different from the step up structure typically deployed during the COVID-19 pandemic. In addition, we present a counterfactual study of how the pandemic would have evolved if herd immunity was reached during the second wave in the county of Los Angeles, California. Finally, we study a case of three interacting counties with and without a governing state.