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In the event of epidemics, ensuring adequate air exchange and airflow direction is essential to reduce the air-borne transmission of infectious agents in buildings. In this study, we strove to identify effective ventilation strategies to reduce the risk of infection by COVID-19 inside buildings. To do so, we developed a multi-route transmission model of SARS-CoV-2 (INDALO®-COVID) which was used to evaluate the risk of infection. This study enabled us to quantify the impact of two preventive measures (installation of a mobile air purifier and increased air renewal via the air purification unit) on the risk of COVID-19 infection in a nursing home. Within the context of this study, the use of an air purifier in the rooms of residents with COVID-19 appears to be the most effective measure to reduce the viral load potentially transported to other areas of the building, and thus to reduce the risk of COVID-19 infection among all residents. The digital model developed is a versatile and ready-to-use solution, which can be used to compare preventive measures and design/renovation choices for different types of buildings and uses.