Mice with Induced Pulmonary Comorbidities Display Severe Lung Inflammation and Mortality following Exposure to SARS-CoV-2

Falach, Reut; Bar-On, Liat; Lazar, Shlomi; Kadar, Tamar; Mazor, Ohad; Aftalion, Moshe; Gur, David; Shifman, Ohad; Israeli, Ofir; Cohen-Gihon, Inbar; Zaide, Galia; Gutman, Hila; Evgy, Yentl; Vagima, Yaron; Makdasi, Efi; Stein, Dana; Rosenfeld, Ronit; Alcalay, Ron; Zahavy, Eran; Levy, Haim; Glinert, Itai; Ben-Shmuel, Amir; Israely, Tomer; Melamed, Sharon; Politi, Boaz; Achdout, Hagit; Yitzhaki, Shmuel; Kronman, Chanoch; Sabo, Tamar

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.