Nevertheless, efforts have successfully created various mouse COVID-19 models by genetic approaches (Muñoz-Fontela et al. 2020; Zeiss et al. 2021), such as replacement of the mouse ace2 with the corresponding human ACE2. It should be emphasized that mutations of the receptor binding domain of SARS-CoV-2 is recognized to be critical for increased transmissibility and even increased morbidity and mortality (Greaney et al. 2021; Jackson et al. 2021; Leung et al. 2020; Guruprasad 2021). This evidence concerns the gene ACE2 and COVID-19.