Comparison of model‐specific histopathology in mouse models of COVID‐19

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has been identified as the causative agent of the current coronavirus disease 2019 pandemic. Development of animal models that parallel the clinical and pathologic features of disease are highly essential to understanding the pathogenesis of SARS‐CoV‐2 infection and the development of therapeutics and prophylactics. Several mouse models that express the human angiotensin converting enzyme 2 (hACE2) have been created, including transgenic and knock‐in strains, and viral vector‐mediated delivery of hACE2. However, the comparative pathology of these mouse models infected with SARS‐CoV‐2 are unknown. Here, we perform systematic comparisons of the mouse models including K18‐hACE2 mice, KI‐hACE2 mice, Ad5‐hACE2 mice and CAG‐hACE2 mice, which revealed differences in the distribution of lesions and the characteristics of pneumonia induced. Based on these observations, the hACE2 mouse models meet different needs of SARS‐CoV‐2 researches. The similarities or differences among the model‐specific pathologies may help in better understanding the pathogenic process of SARS‐CoV‐2 infection and aiding in the development of effective medications and prophylactic treatments for SARS‐CoV‐2. Highlights We systematically describe and compare the histopathological changes at acute stage of the four types of SARS‐CoV‐2 infection hACE2 mouse models, which provides a framework that may help in better understanding the pathogenic process of SARS‐CoV‐2 infection.