Phodopus roborovskii SH101 as a systemic infection model of SARS-CoV-2

Abstract

AbstractSevere acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide threat with its unusually high transmission rates and rapid evolution into diverse strains. Unlike typical respiratory viruses, SARS-CoV-2 frequently causes systemic infection by breaking the boundaries of the respiratory systems. The development of animal models recapitulating the clinical manifestations of COVID-19 is of utmost importance not only for the development of vaccines and antivirals but also for understanding the pathogenesis. However, there has not been developed an animal model for systemic infection of SARS-CoV-2 representing most aspects of the clinical manifestations of COVID-19 with systemic symptoms. Here we report that a hamster strain of Phodopus roborovskii SH101, a laboratory inbred hamster strain of P. roborovskii, displayed most symptoms of systemic infection upon SARS-CoV-2 infection as in the case of the human counterpart, unlike current COVID-19 animal models. P. roborovskii SH101 post-infection of SARS-CoV-2 represented most clinical symptoms of COVID-19 such as snuffling, dyspnea, cough, labored breathing, hunched posture, progressive weight loss, and ruffled fur, in addition to high fever following shaking chills. Histological examinations also revealed a serious right-predominated pneumonia as well as slight organ damages in the brain and liver, manifesting systemic COVID-19 cases. Considering the merit of a small animal as well as its clinical manifestations of SARS-CoV-2 infection in human, this hamster model seems to provide an ideal tool to investigate COVID-19.Author summaryAlthough the current animal models supported SARS-CoV-2 replication and displayed varying degrees of illness after SARS-CoV-2 infection, the infections of SARS-CoV-2 were mainly limited to the respiratory systems of these animals, including hACE2 transgenic mice, hamsters, ferrets, fruit bats, guinea pigs, African green monkey, Rhesus macaques, and Cynomolgus macaques. While these animal models can be a modest model for the respiratory infection, there is a clear limit for use them in the study of COVID-19 that also displays multiple systemic symptoms. Therefore, the development of an animal model recapitulating COVID-19-specific symptoms such as the right-predominated pneumonia would be the utmost need to overcome the imminent threat posed by COVID-19. We identified a very interesting hamster strain, Phodopus roborovskii SH101, which mimics almost all aspects of the clinical manifestations of COVID-19 upon SARS-CoV-2 infection. Unlike the current animal models, SARS-CoV-2-infected P. roborovskii SH101 not only displayed the symptoms of respiratory infection but also clinical manifestations specific to human COVID-19 such as high fever following shaking chills, serious right-predominated pneumonia, and minor organ damages in the brain and liver.