The search for a COVID-19 animal model

With the pandemic [caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2)] continuing worldwide, many labs are competing to find appropriate animal models to study coronavirus disease 2019 (COVID-19) attributed to the virus. The optimal animal model will, of course, depend on the scientific question. Authors [see 1st attached article] found that young as well as aged cynomolgus macaques, infected with SARS-CoV-2, discharged virus from the upper and lower respiratory tract, but failed to develop severe clinical symptoms. Authors [see 2nd attached article] found a high viral burden and airborne transmission of SARS-CoV-2 between cats and ferrets, highlighting an important animal model for SARS-CoV-2 transmission. These two animal models offer distinctly different platforms — for asking specific questions about SARS-CoV-2 infection, induction of disease, and transmission.

Humans with COVID-19 display a very wide range of disease symptoms — from asymptomatic to severe pneumonia, but also sometimes problems in heart, kidney, skin, and brain. Extrapolating data from a single animal model, to the varied disease outcomes in humans, is therefore not only challenging — but can potentially be misleading. Studies examining efficacy of vaccines and antiviral drugs traditionally use models of severe disease; however, this may not mimic the common pathology in the majority of COVID-19 patients, and could limit our understanding of other important questions, including infection dynamics and transmission.

Previous work on other emerging coronaviruses [e.g. Middle East respiratory syndrome–coronavirus (MERS-CoV) and SARS-CoV-1] have included mouse, hamster, ferret, monkey, and camel as animal models. Although mouse is the preferred research animal model — because of the lower cost of animal facilities, short generation time, and wealth of reagents available for studying this species — early reports indicate that mouse is unsuitable for SARS-CoV-2 infection (likely due to receptor incompatibility). Therefore, humanized transgenic mice — that express the human angiotensin-converting enzyme-2 (hACE2), which is the host cell receptor for SARS-CoV-2 entry — will be useful to examine COVID-19. However, preliminary work with hACE2-transgenic mice demonstrates susceptibility, but only limited disease severity.

Authors [see 1st attached article] investigated susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2; they found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks — but ferrets and cats are permissive to infection, plus cats are susceptible to airborne transmission. Authors [see 2nd attached article] inoculated cynomolgus macaques with SARS-CoV-2 or MERS–CoV and compared the pathology and virology with historical reports of SARS-CoV infections. In SARS-CoV-2–infected macaques, virus was excreted from nose and throat in the absence of clinical signs — and detected in type I and II pneumocytes in foci of diffuse alveolar damage and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosal membranes. In SARS-CoV-2 infections, lung lesions were typically more severe, whereas they were milder in MERS-CoV infection (the virus detected mainly in type II pneumocytes). Data from these two articles may be helpful in providing new models to test preventive and therapeutic strategies for understanding COVID-19 better. 😊


Science 29 May 2020; 368: 1012-15 & 1016-1019 + editorial pp 942-943

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