K18-hACE2 mice can be infected with the SARS-CoV-2 virus, resulting in severe disease characterized by weight loss, rapid respiration, hunched posture, and immobility. This strain responds to viral attack in a dose-dependent manner, thus allowing the study of severe acute respiratory disease in mice heavily infected by high doses of the virus, as well as the long-term effects of low doses of mild infection. The model should be handled in strict accordance with the guidelines for the prevention of SARS-CoV-2 virus infection in humans as specified by CDC&ABSA&WHO, and appropriate personal protective equipment (PPE) and handling methods should always be used when using these mice for research.