Background After 18 months of responding to the COVID-19 pandemic, there is still no agreement on the optimal combination of mitigation strategies. The efficacy and collateral damage of pandemic policies are dependent on constantly evolving viral epidemiology as well as the volatile distribution of socioeconomic and cultural factors. This study proposes a data-driven approach to quantify the efficacy of the type, duration, and stringency of COVID-19 mitigation policies in terms of transmission control and economic loss, personalised to individual countries. Methods We present What If…?, a deep learning pandemic-policy-decision-support algorithm simulating pandemic scenarios to guide and evaluate policy impact in real time. It leverages a uniquely diverse live global data-stream of socioeconomic, demographic, climatic, and epidemic trends on over a year of data (04/2020–06/2021) from 116 countries. The economic damage of the policies is also evaluated on the 29 higher income countries for which data is available. The efficacy and economic damage estimates are derived from two neural networks that infer respectively the daily R-value (RE) and unemployment rate (UER). Reinforcement learning then pits these models against each other to find the optimal policies minimising both RE and UER. Findings The models made high accuracy predictions of RE and UER (average mean squared errors of 0.043 [CI95: 0.042–0.044] and 4.473% [CI95: 2.619–6.326] respectively), which allow the computation of country-specific policy efficacy in terms of cost and benefit. In the 29 countries where economic information was available, the reinforcement learning agent suggested a policy mix that is predicted to outperform those implemented in reality by over 10-fold for RE reduction (0.250 versus 0.025) and at 28-fold less cost in terms of UER (1.595% versus 0.057%). Conclusion These results show that deep learning has the potential to guide evidence-based understanding and implementation of public health policies.

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