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Studies have reported significant reductions in air pollutant levels due to the COVID-19 outbreak worldwide due to global lockdowns. Nevertheless, all of the reports are limited compared to data from the same period over the past few years, providing mainly an overview of past events, with no future predictions. Lockdown level can be directly related to the number of new COVID-19 cases, air pollution, and economic restriction. As lockdown status varies considerably across the globe, there is a window for mega-cities to determine the optimum lockdown flexibility. To that end, firstly, we employed four different Artificial Neural Networks (ANN) to examine the compatibility to the original levels of CO, O 3 , NO 2 , NO, PM 2.5 , and PM 10 , for São Paulo City, the current Pandemic epicenter in South America. After checking compatibility, we simulated four hypothetical scenarios: 10%, 30%, 70%, and 90% lockdown to predict air pollution levels. To our knowledge, ANN have not been applied to air pollution prediction by lockdown level. Using a limited database, the Multilayer Perceptron neural network has proven to be robust (with Mean Absolute Percentage Error ∼ 30%), with acceptable predictive power to estimate air pollution changes. We illustrate that air pollutant levels can effectively be controlled and predicted when flexible lockdown measures are implemented. The models will be a useful tool for governments to manage the delicate balance among lockdown, number of COVID-19 cases, and air pollution.

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