Deep-ultraviolet (DUV) disinfection technology provides an expeditious and efficient way to suppress the transmission of coronavirus disease 2019 (COVID-19). However, the influences of viral variants (Delta and Omicron) and low temperatures on the DUV virucidal efficacy are still unknown. Here, we developed a reliable and uniform planar light source comprised of 275-nm light-emitting diodes (LEDs) to investigate the effects of these two unknown factors and delineated the principle behind different disinfection performances. We found the lethal effect of DUV at the same radiation dose was reduced by the cryogenic environment, and a negative-U large-relaxation model was used to explain the difference in view of the photoelectronic nature. The chances were higher in the cryogenic environment for the capture of excited electrons within active genetic molecules back to the initial photo-ionised positions. Additionally, the variant of Omicron required a significantly higher DUV dose to achieve the same virucidal efficacy, and this was thanks to the genetic and proteinic characteristics of the Omicron. The findings in this study are important for human society using DUV disinfection in cold conditions (e.g., the food cold chain logistics and the open air in winter), and the relevant DUV disinfection suggestion against COVID-19 is provided.