Table 4.

Susceptibility, symptoms, viral replication and pathology in hACE2 transgenic mice infected with SARS-CoV and SARS-CoV-2

Animal Species/Strain	Susceptibility and Symptoms	Viral replication/distribution in organs	Histopathological changes	Ref
K18-hACE2 mice (infected with 2.3 × 104 PFU of SARS-CoV strain)	▪ Shows severe signs of disease like weight loss, lethargy and labored breathing ▪ SARS-CoV not transmitted from infected to non-infected mice	▪ viral titers detected in lungs, brain ▪ Virus not detected in liver, small intestine and kidneys ▪ Detection of viral antigen in cerebrum, cerebellum, thalamus, brainstem, olfactory balb	▪ Perivascular and peribronchiolar inflammation ▪ Epithelial cell sloughing, hemorrhage, congestion in alveolar septa ▪ Intense neutrophilic infiltration, necrotizing bronchopnemmonia ▪ Upregulation of cytokines and chemokines in lungs and brain	McCray 2007
hACE2-AC70 mice (infected with 2 × 105/103 TCID50 of SARS-CoV strain)	▪ Symptoms of weight loss, lethargy, ruffled fur, shallow breathing ▪ 100% Mortality 8-day PI	▪ Viral replication detected in lungs and brain, low level of viremia detected in blood ▪ Virus could be detected in bowels, nasal washes and liver but not in throat swabs ▪ Virus not detected in heart, kidneys, urine, spleen	▪ Moderate interstitial pneumonitis, alveolar wall thickening, presence of cellular debris and macrophages in alveolar sacks and airways ▪ Cytoplasmic swelling, blebbing in bronchoepithelial cells ▪ Viral antigen detected in ganglion cells and vascular smooth muscles of lungs and blood vessels, glial cells of CNS ▪ Elevated levels of cytokines and chemokines in lungs	Tseng 2007
HFH4-hACE2 mice (infected with 105 PFU of SARS-CoV urbani strain)	▪ Rapid weight loss, and death between day 4–5	▪ Viral replication in brain, lungs	▪ Not reported	Menachery 2016
hACE2-mice (infected with 105 TCID50 of SARS-CoV-2 strain)	▪ Slight weight loss and bristled fur, no other clinical signs reported	▪ Viral RNA detectable in lungs, intestine ▪ Virus could be isolated from lungs in Vero E6 cell line ▪ Viral antigens not detected in kidneys, liver, spleen, myocardium, testis or brain	▪ Dark reddish-purple areas and nodules found in lungs ▪ Moderate interstitial pneumonia, thickening of alveolar septa, infiltration of inflammatory cells in alveolar cavities, high infiltration of macrophages, neutrophils and lymphocytes in perivascular region ▪ Swollen, degenerated Broncho epithelial cells	Bao 2020b