Lowering the potential of airborne disease transmission in school buildings is especially important in the wake of the COVID-19 pandemic. The benefits of increased ventilation and filtration for reducing disease transmission compared to drawbacks of reduced thermal comfort and increased energy consumption and electricity demand are not well described. A comprehensive simulation of outdoor air ventilation rates and filtration methods was performed with a modified Wells-Riley equation and EnergyPlus building simulation to understand the trade-offs between infection probability and energy consumption for a simulated classroom in 13 cities across the US. A packaged heating, ventilation, and air conditioning unit was configured, sized, and simulated for each city to understand the impact of five ventilation flow rates and three filtration systems. Higher ventilation rates increased energy consumption and resulted in a high number of unmet heating and cooling hours in most cities (excluding Los Angeles and San Francisco). On average, across the 13 cities simulated, annual energy consumed by an improved filtration system was 31% lower than the energy consumed by 100% outdoor air ventilation. In addition, the infection probability was 29% lower with improved filtration.