Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review
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RESEARCH
Open Access
Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review Salleh N. Ehaideb, Mashan L. Abdullah, Bisher Abuyassin and Abderrezak Bouchama*
Abstract 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 human 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. Result: Thirteen peer-reviewed studies and 14 preprints met the 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 nonhuman primates, hamsters, and mice. Notably, none of the animals unveiled a 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. Keywords: COVID-19, SARS-CoV-2, Animal models, Review, Non-human primate, Rodent, Hamster, Ferrets
Background Coronavirus disease 2019 (COVID-19) is a febrile respiratory illness due to a novel viral pathogen severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) [1, 2]. COVID-19 can progress to acute respiratory distress syndrome (ARDS), multiple organ dysfunction/failure * Correspondence: [email protected] Experimental Medicine Department, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
(MOSD) including central nervous system alteration, acute kidney injury, cardiovascular failure, liver injury, and coagulopathy culminating in death [2–9]. SARS-CoV-2 is a beta coronavirus that binds with a high affinity to angiotensin-converting enzyme (ACE) 2 receptor and uses the transmembrane serine protease (TMPRSS) 2 as co-receptor to gain entry to cel
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