Hamsters Expressing Human Angiotensin-Converting Enzyme 2 Develop Severe Disease following Exposure to SARS-CoV-2

Abstract

The rapid emergence of SARS-CoV-2 has created a global health emergency. While most human SARS-CoV-2 disease is mild, some people develop severe, life-threatening disease.

The neuroinvasiveness, neurotropism, and neurovirulence of SARS-CoV-2

“…RNA in the CNS as well as inflammation and changes in the neurovascular system [17,30]. Although the Syrian hamster has been used most frequently in hamster studies, it was recently shown that, in Roborovski dwarf hamsters, inbred hamsters, transgenic hamsters expressing human ACE2, and obese hamsters, SARS-CoV-2 infection resulted in more severe disease and systemic spread, including virus spread to the CNS [88][89][90][91].…”

Animal models for studying COVID-19, prevention, and therapy: Pathology and disease phenotypes

“…In some models such as hACE2 hamsters, pulmonary lesions are localized predominantly in bronchi and bronchioles, whereas in other models such as hACE2 mice, the lesions are predominantly in the alveoli. 27 Although pulmonary vascular changes do occur including endothelial damage/endotheliitis, vasculitis, microthrombi, and NETs, the severity of these findings are generally limited in animal models. Virus cytopathic-like changes observed in animal models can also be associated with regeneration of injured airway epithelium and need further characterization by IHC/ISH and/or ultrastructural evaluation for confirmation.…”

“… 10 , 25 Damage (inflammation and necrosis) to olfactory epithelium as well as respiratory epithelium of the nasal cavity is observed in hACE2-expressing mouse and hamster models. 13 , 27 …”

“… 61 Among animal models, encephalitis, as well as associated neurological signs (e.g., ataxic gait, tremors, or anosmia) have been reported in K18-hACE2 mice following SARS-CoV-2 infections; 91 however, neurological infection by SARS-CoV-2 is less severe in mice than for SARS-CoV. 50 SARS-CoV-2-related histologic lesions (e.g., inflammation and necrosis) in the central nervous system is reported in the rhesus macaque and Tg hACE2 hamster models, 19 , 27 however, no neurological signs were observed. Recently, non-mammalian models, such as zebrafish, were used to investigate neurologic features of COVID-19.…”

“… 30 , 43 , 45 , 56 Currently, reports on animal models exhibiting the above-mentioned pathological manifestations are rare ( Table 2 ). Recently, SARS-CoV-2-related lesions in the heart (myocarditis, ventricular hypertrophy, and microthrombi) and kidney (tubular inflammation) was observed in hamster models (wild-type or Tg hACE2) 26 , 27 and in the liver of ferrets (hepatitis). 68 Extrapulmonary effects in wild type hamsters or ferrets are mostly transcriptomic or lipidomic changes with less severe microscopic alterations than in humans and live virus is not detected in these organs.…”