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Background: Containment measures slowed the spread of COVID-19 but led to a global economic crisis. We establish a reinforcement learning (RL) algorithm that balances disease control and economic activities., Methods: To train the RL agent, we design an RL environment with 4 semi-connected regions to represent the COVID-19 epidemic in Tokyo, Osaka, Okinawa, and Hokkaido, Japan. Every region is governed by a Susceptible-Exposed-Infected-Quarantined-Removed (SEIQR) model and has a transport hub to connect with other regions. The allocation of the synthetic population and inter-regional traveling is determined by population-weighted density. The agent learns the best policy from interacting with the RL environment, which involves obtaining daily observations, performing actions on individual movement and screening, and receiving feedback from the reward function. After training, we implement the agent into RL environments describing the actual epidemic waves of the four regions to observe the agent's performance., Results: For all epidemic waves covered by our study, the trained agent reduces the peak number of infectious cases and shortens the epidemics (from 165 to 35 cases and 148 to 131 days for the 5th wave). The agent is generally strict on screening but easy on movement, except for Okinawa, where the agent is easy on both actions. Action timing analyses indicate that restriction on movement is elevated when the number of exposed or infectious cases remains high or infectious cases increase rapidly, and stringency on screening is eased when the number of exposed or infectious cases drops quickly or to a regional low. For Okinawa, action on screening is tightened when the number of exposed or infectious cases increases rapidly., Conclusions: Our experiments exhibit the potential of the RL in assisting policy-making and how the semi-connected SEIQR models establish an interactive environment for imitating cross-regional human flows., (© 2024. The Author(s).)