The mechanistic factors hypothesized to be key drivers for the loss of infectivity of viruses in the aerosol phase often remain speculative. Using a next-generation bioaerosol technology, we report measurements of the aero-stability of several SARS-CoV-2 variants of concern in aerosol droplets of well-defined size and composition at high (90%) and low (40%) relative humidity (RH) upwards of 40 min. When compared with the ancestral virus, the infectivity of the Delta variant displayed different decay profiles. At low RH, a loss of viral infectivity of approximately 55% was observed over the initial 5 s for both variants. Regardless of RH and variant, greater than 95% of the viral infectivity was lost after 40 min of being aerosolized. Aero-stability of the variants correlate with their sensitivities to alkaline pH. Removal of all acidic vapours dramatically increased the rate of infectivity decay, with 90% loss after 2 min, while the addition of nitric acid vapour improved aero-stability. Similar aero-stability in droplets of artificial saliva and growth medium was observed. A model to predict loss of viral infectivity is proposed: at high RH, the high pH of exhaled aerosol drives viral infectivity loss; at low RH, high salt content limits the loss of viral infectivity.