BACKGROUND: To combat COVID-19, curb the pandemic, and manage containment, governments around the world are turning to data collection and population monitoring for analysis and prediction. The massive data generated through the use of big data and artificial intelligence can play an important role in addressing this unprecedented global health and economic crisis. OBJECTIVES: The objective of this work is to develop an expert system that combines several solutions to combat COVID-19. The main solution is based on a new developed software called General Guide (GG) application. This expert system allows us to explore, monitor, forecast, and optimize the data collected in order to take an efficient decision to ensure the safety of citizens, forecast, and slow down the spread’s rate of COVID-19. It will also facilitate countries’ interventions and optimize resources. Moreover, other solutions can be integrated into this expert system, such as the automatic vehicle and passenger sanitizing system equipped with a thermal and smart High Definition (HD) cameras and multi-purpose drones which offer many services. All of these solutions will facilitate lifting COVID-19 restrictions and minimize the impact of this pandemic. METHODS: The methods used in this expert system will assist in designing and analyzing the model based on big data and artificial intelligence (machine learning). This can enhance countries’ abilities and tools in monitoring, combating, and predicting the spread of COVID-19. RESULTS: The results obtained by this prediction process and the use of the above mentioned solutions will help monitor, predict, generate indicators, and make operational decisions to stop the spread of COVID-19. CONCLUSIONS: This developed expert system can assist in stopping the spread of COVID-19 globally and putting the world back to work.