Animal models of COVID‐19 hyper‐inflammation

De Novo Whole Genome Assembly of the Roborovski Dwarf Hamster (Phodopus roborovskii) Genome, an Animal Model for Severe/Critical COVID-19

“…By histopathology, massive alveolar destruction and microthrombosis are evident in the lungs of infected animals while other organs, including the brain, do not seem to be primarily involved in disease development. The rapid onset and fulminant course of pulmonary disease makes this species a valuable model to study severe courses of COVID-19 in humans and test therapies and vaccinations in the background of severe disease (Muñoz-Fontela et al 2020;Gantier 2021). The novelty of this model however entails a problematic lack of reagents and tools to study immune reactions and other host factors.…”

“…Mesocricetus (golden hamster) species (Wilson et al 2009). The Roborovski dwarf hamster is, so far, the only non-transgenic animal that consistently develops severe disease and hyper-inflammation of the lung following infection with SARS-CoV-2 (Gantier 2021;Muñoz-Fontela et al 2020). Clinical signs develop within the first 48 hours following infection and include drastic reduction in body temperature, substantial weight loss, forced breathing, ruffled fur and lethargy.…”

Animal models and COVID‐19: Mechanism and comorbidities

“…I appreciated the recent commentary 'Animal models of COVID-19 hyper-inflammation' by Gantier published in Respirology. 1 The author described the importance and potential of animal models, especially mouse models, for the investigation of coronavirus disease 2019 (COVID-19). Dr Gantier touched on the potential for animal models for investigations on the mechanism of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.…”

Reply

“…As stated in my commentary on the topic, assessing the outcome of SARS-CoV2 infection in ACE2-expressing mice, for instance, lacking TLR3 or IRF7 is likely to lead to hyper-inflammation in these animals, based on recent genomic studies in patients with life-threatening COVID-19 pneumonia. 3 While these sensitized mouse models may indeed be very helpful to better understand how specific pathways or preexisting respiratory/metabolic conditions worsen the evolution of the disease, or their long-term effects, the degree of severity and penetrance of COVID-19 conferred by adenovirus or AAV sensitization may not be sufficient for the investigation of antiviral or anti-inflammatory treatments, readily achievable with the K18-hACE2 mice or Roborovski dwarf hamsters. 3 As such, SARS-CoV-2 infections in mouse models infected with adenovirus or AAV expressing human ACE2 are not lethal, and only show moderate weight loss.…”

“…3 While these sensitized mouse models may indeed be very helpful to better understand how specific pathways or preexisting respiratory/metabolic conditions worsen the evolution of the disease, or their long-term effects, the degree of severity and penetrance of COVID-19 conferred by adenovirus or AAV sensitization may not be sufficient for the investigation of antiviral or anti-inflammatory treatments, readily achievable with the K18-hACE2 mice or Roborovski dwarf hamsters. 3 As such, SARS-CoV-2 infections in mouse models infected with adenovirus or AAV expressing human ACE2 are not lethal, and only show moderate weight loss. 1,2 In addition, pre-infection with adenovirus or AAV used to express human ACE2 has the capacity to prime antiviral responses through DNA-sensing pathways such as the cGAS-STING pathway, 4 which can influence the later infection by SARS-CoV2.…”