A Meta-Analysis of Rhesus Macaques (Macaca mulatta), Cynomolgus Macaques (Macaca fascicularis), African green monkeys (Chlorocebus aethiops), and Ferrets (Mustela putorius furo) as Large Animal Models for COVID-19

Animal models are at the forefront of biomedical research for studies of viral transmission, vaccines, and pathogenesis, yet the need for an ideal large animal model for COVID-19 remains. We used a meta-analysis to evaluate published data relevant to this need. Our literature survey contained 22 studies with data relevant to the incidence of common COVID-19 symptoms in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), African green monkeys (Chlorocebus aethiops), and ferrets (Mustela putorius furo). Rhesus macaques had leukocytosis on Day 1 after inoculation and pneumonia on Days 7 and 14 after inoculation, in frequencies that were similar enough to humans to reject the null hypothesis of a Fisher exact test. However, the differences in overall presentation of disease were too different from that of humans to successfully identify any of these 4 species as an ideal large animal of COVID-19. The greatest limitation to the current study is a lack of standardization in experimentation and reporting. To expand our understanding of the pathology of COVID-19 and evaluate vaccine immunogenicity, we must extend the unprecedented collaboration that has arisen in the study of COVID-19 to include standardization of animal-based research in an effort to find the optimal animal model.