Figure 3.

Illustrates various animal models of COVID-19 and the mode of infection. Models were useful in displaying different levels of clinical disease severity once sensitized to SARS-CoV-2 infection. Top left: Mice engineered to express hACE2 gene using k18 promoter. SARS-CoV-2 intranasal inoculation & ACE-2 transfection was shown to cause clinical symptoms (severe lung infection, anosmia) with mild extrapulmonary symptoms (GI, neurological). Top right: Aged, wild-type mice were serially passaged with intranasal SARS-CoV-2. Over time, viral generations eventually were able to bind to mACE-2 leading to clinical interstitial pneumonia and positive titers of neutralizing antibodies. Bottom: Mouse ACE-2 promoter with Human ACE-2 coding sequence were injected into pronuclei leading to mACE-2/hACE-2 susceptible to SARS-CoV-2 infection. hACE-2 receptors were expressed in lungs, kidneys, intestines & heart with mild clinical symptoms (mild weight loss, bristled fur).