Induced pulmonary comorbidities render CD-1 mice sensitive to SARS-CoV-2
Falach, R.; Bar-On, L.; Lazar, S.; Kadar, T.; Mazor, O.; Aftalion, M.; Gur, D.; Shifman, O.; Israeli, O.; Cohen-Gihon, I.; Zaida, G.; Gutman, H.; Evgy, Y.; Vagima, Y.; Makdasi, E.; Stein, D.; Rosenfeld, R.; Alcalay, R.; Zahavy, E.; Levy, H.; Glinert, I.; Ben-Shmuel, A.; Israely, T.; Melamed, S.; Politi, B.; Achdout, H.; Yitzhaky, S.; Kronman, C.; Sabo, T.
Show abstract
Severe manifestations of COVID-19 are mostly restricted to people with comorbidities. Here we report that induced mild pulmonary morbidities render SARS-CoV-2-refractive CD-1 mice to be susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low-doses of the acute-lung-injury stimulants bleomycin or ricin caused a severe disease in CD-1 mice, manifested by sustained body weight loss and mortality rates of >50%. Further studies revealed markedly higher levels of viral RNA in the lungs, heart and serum of low-dose-ricin pretreated, as compared to non-pretreated mice. Notably, the deleterious effects of SARS-CoV-2 infection were effectively alleviated by passive transfer of polyclonal or monoclonal antibodies generated against SARS-CoV-2 RBD. Thus, viral cell entry in the sensitized mice seems to involve viral RBD binding, albeit by a mechanism other than the canonical ACE2-mediated uptake route. In summary, we present a novel mice-based animal model for the study of comorbidity-dependent severe COVID-19.
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