This ongoing global pandemic of the COVID-19 has generated a significant international concern for our respiratory health. For instance, the breakout of the COVID-19 pandemic was directly linked to the spread of infectious particles in indoor environments between humans, underlining the significance of rigorous and effective actions to limit the transmission of diseases. Recently, Mucormycosis infections in COVID-19 patients have been identified. This investigation aims to investigate potential infection control HVAC solutions for indoor environments, as well as their core mechanisms for reducing infectious disease risk through simulation models of a valid building in a hot climatic region. Considering recent international recommendations, the investigation relies on a methodology of testing a validated building energy model to several systems in the light of infectious diseases prevention. All proposed models are exposed to cost analysis in line with carbon emissions, and indoor thermal conditions. The analysis outlined through parametric simulations, the effectiveness of the proposed DOAS in supplying 100% fresh ventilation air and enhancing the control of the indoor relative humidity simultaneously. Finally, through an enviro-economic assessment, the study concluded that the DOAS model reduced the CO₂ emissions to 691 tons, with a potential of reducing HVAC and whole-building energy use by 37% and 16%, respectively in the hot arid climate, with a return on investment of about 6%.