Establishment of SARS-CoV-2 respiratory tract infection model in CAG promoter-driven hACE2 transgenic mice

Abstract

COVID-19, caused by SARS-CoV-2, has spread worldwide with dire consequence. Vaccine is just not enough to suppress to this pandemic, and it is desired to develop the prophylactic and therapeutic agents for preventing the spread of infection and severity. Therefore, it is extremely important to propose therapeutic strategies by using pathological models. In this study, we established an animal model with highly susceptible to SARS-CoV-2 via the intratracheal tract infection in CAG-promoter-driven human angiotensin-converting enzyme 2 transgenic (CAG-hACE2) mice that more than 15 copies of hACE2 genes were tandemly integrated into the mouse genome. The CAG-hACE2 mice showed several severe symptoms of SARS-CoV-2 infection, with definitive weight loss and subsequent death. Acute pneumonia with elevated cytokine and chemokine levels was observed at an early stage of infection in CAG-hACE2 mice infected with SARS-CoV-2. In the developed model, administration of remdesivir, which is antiviral agent, or injection of plasma from immunized mice prevented body weight loss and lethality due to infection with SARS-CoV-2. These results indicated that a highly susceptible model of SARS-CoV-2 infection in CAG-hACE2 mice via the intratracheal tract is suitable for evaluating antibody therapeutics and medicines.