A mouse model for SARS-CoV-2-induced acute respiratory distress syndrome

The COVID-19 pandemic has covered more than 200 countries and regions around the world since its outbreak in January 2020. To date, the SARS-CoV-2 virus has caused >1.2 million deaths. The mortality rate of COVID-19 is closely concerned with the clinical symptoms of the patients from mild-to-severe disease. Notably, in its most severe form, COVID-19 leads to life-threatening pneumonia and acute respiratory distress syndrome (ARDS), which is mostly accompanied by a hyperactive immune response called “cytokine storm” and has high death rates from 40 to 50%. 1 To elucidate the mechanisms of COVID-19 immunity and pathogenesis, researchers have developed several SARS-CoV-2 mouse models using transgenic mouse lines expressing hACE2 by the nasal inoculation of SARS-CoV-2. 2 , 3 However, these models showed mild-to-moderate interstitial pneumonia with mononuclear cell infiltration, 2 , 3 the pathological features of SARS-CoV-2-induced ARDS in humans, such as the disruption of lung tissues with apparent cell death, neutrophil infiltration, proteinaceous debris, hemorrhage, thrombi, and hyaline membranes-like changes, were rarely found in nasal inoculation of SARS-CoV-2 mouse model. 2 , 3 Thus, these models failed to recapitulate the acute and severe form of lung injury, especially, its progression to ARDS. Therefore, the establishment of laboratory animal models for ARDS is important to support the studies for COVID-19 progression and treatment evaluation.