Currently, human entry receptor angiotensin-converting enzyme 2 (hACE2) transgenic mice are being used to study SARS-CoV-2 infection and pathogenesis, but these transgenic mice are limited to only one genetic background and are not widely available. Thus, another mouse model of SARS-CoV-2 using adeno-associated virus (AAV)-mediated expression of hACE2 has been developed. These AAV-hACE2 mice are capable of allowing for viral replication and demonstrate the pathogenicity of the virus as seen in patients with COVID-19.