Purpose Biocontaminants represent higher risks to occupants' health in shared spaces. Natural ventilation is an effective strategy against indoor air biocontamination. However, the relationship between natural ventilation and indoor air contamination requires an in-depth investigation of the behavior of airborne infectious diseases, particularly concerning the contaminant's viral and aerodynamic characteristics. This research investigates the effectiveness of natural ventilation in preventing infection risks for coronavirus disease (COVID-19) through indoor air contamination of a free-running, naturally-ventilated room (where no space conditioning is used) that contains a person having COVID-19 through building-related parameters. Design/methodology/approach This research adopts a case study strategy involving a simulation-based approach. A simulation pipeline is implemented through a number of design scenarios for an open office. The simulation pipeline performs integrated contamination analysis, coupling a parametric 3D design environment, computational fluid dynamics (CFD) and energy simulations. The results of the implemented pipeline for COVID-19 are evaluated for building and environment-related parameters. Study metrics are identified as indoor air contamination levels, discharge period and the time of infection. Findings According to the simulation results, higher indoor air temperatures help to reduce the infection risk. Free-running spring and fall seasons can pose higher infection risk as compared to summer. Higher opening-to-wall ratios have higher potential to reduce infection risk. Adjacent window configuration has an advantage over opposite window configuration. As a design strategy, increasing opening-to-wall ratio has a higher impact on reducing the infection risk as compared to changing the opening configuration from opposite to adjacent. However, each building setup is a unique case that requires a systematic investigation to reliably understand the complex airflow and contaminant dispersion behavior. Metrics, strategies and actions to minimize indoor contamination risks should be addressed in future building standards. The simulation pipeline developed in this study has the potential to support decision-making during the adaptation of existing buildings to pandemic conditions and the design of new buildings. Originality/value The addressed need of investigation is especially crucial for the COVID-19 that is contagious and hazardous in shared indoors due to its aerodynamic behavior, faster transmission rates and high viral replicability. This research contributes to the current literature by presenting the simulation-based results for COVID-19 as investigated through building-related and environment-related parameters against contaminant concentration levels, the discharge period and the time of infection. Accordingly, this research presents results to provide a basis for a broader understanding of the correlation between the built environment and the aerodynamic behavior of COVID-19.