Mice are normally unaffected by SARS coronavirus 2 (SARS-CoV-2)
infection since the virus does not bind effectively to the murine version of the
angiotensin-converting enzyme 2 (ACE2) receptor molecule. Here, we report that induced mild pulmonary morbidities rendered SARS-CoV-2-refractive CD-1 mice susceptible to this virus. Specifically,
SARS-CoV-2 infection after application of low doses of the
acute lung injury stimulants
bleomycin or
ricin caused severe disease in CD-1 mice, manifested by sustained
body weight loss and mortality rates greater than 50%. Further studies revealed markedly higher levels of
viral RNA in the lungs, heart, and serum of low-dose
ricin-pretreated mice compared with non-pretreated mice. Furthermore, lung extracts prepared 2-3 days after
viral infection contained
subgenomic mRNA and virus particles capable of replication only when derived from the pretreated mice. The deleterious effects of
SARS-CoV-2 infection were effectively alleviated by passive transfer of polyclonal or
monoclonal antibodies generated against the SARS-CoV-2 receptor binding domain (RBD). Thus, viral cell entry in the sensitized mice seems to depend on viral RBD binding, albeit by a mechanism other than the canonical ACE2-mediated uptake route. This unique mode of viral entry, observed over a mildly injured tissue background, may contribute to the exacerbation of
coronavirus disease 2019 (COVID-19) pathologies in patients with preexisting morbidities.