A systematic review uncovers a wide-gap between COVID-19 in humans and animal models

Ehaideb, S. N.; Abdullah, M. L.; Abuyassin, B.; Bouchama, A.

Background: Animal models of COVID-19 have been rapidly reported after the start of the pandemic. We aimed to assess whether the newly created models reproduce the full spectrum of humans COVID-19. Methods: We searched the Medline, as well as BioRxiv and MedRxiv preprint servers for original research published in English from January 1, to May 20, 2020. We used the search terms COVID-19 OR SARS-CoV-2 AND, animal models, hamsters, nonhuman primates, macaques, rodent, mice, rats, ferrets, rabbits, cats, and dogs. Inclusion criteria were the establishment of animal models of COVID-19 as an endpoint. Other inclusion criteria were assessment of prophylaxis, therapies, or vaccines, using animal models of COVID-19. Findings: 13 peer-reviewed studies and 14 preprints met inclusion criteria. The animals used were nonhuman primates (n=13), mice (n=7), ferrets (n =4), hamsters (n= 4), and cats (n =1). All animals supported high viral replication in the upper and lower respiratory tract associated with mild clinical manifestations, lung pathology and full recovery. Older animals displayed relatively more severe illness than the younger ones. No animal models developed hypoxemic respiratory failure, multiple organ dysfunction, culminating in death. All species elicited a specific IgG antibodies response to the spike proteins, which were protective against a second exposure. Transient systemic inflammation was observed occasionally in Rhesus macaques, hamsters, and mice. Notably, none of the animals unveiled cytokine storm or coagulopathy. Conclusions: Most of the animal models of COVID-19 recapitulated mild pattern of human COVID-19 with full recovery phenotype. No severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans and animal models.