Characteristics of animal models for COVID‐19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the causative agent of coronavirus disease 2019 (COVID‐19), the most consequential pandemic of this century, threatening human health and public safety. SARS‐CoV‐2 has been continuously evolving through mutation of its genome and variants of concern have emerged. The World Health Organization R&D Blueprint plan convened a range of expert groups to develop animal models for COVID‐19, a core requirement for the prevention and control of SARS‐CoV‐2 pandemic. The animal model construction techniques developed during the SARS‐CoV and MERS‐CoV pandemics were rapidly deployed and applied in the establishment of COVID‐19 animal models. To date, a large number of animal models for COVID‐19, including mice, hamsters, minks and nonhuman primates, have been established. Infectious diseases produce unique manifestations according to the characteristics of the pathogen and modes of infection. Here we classified animal model resources around the infection route of SARS‐CoV‐2, and summarized the characteristics of the animal models constructed via transnasal, localized, and simulated transmission routes of infection.

A highly susceptible hACE2-transgenic mouse model for SARS-CoV-2 research

“…COVID-19 involves complex host-pathogen interactions; therefore, it is necessary to develop animal models that can provide measurable readouts for potential interventions ( Johansen et al, 2020 ; Muñoz-Fontela et al, 2020 ; Villano, 2021 ; Choudhary et al, 2022 ). To rapidly evaluate these potential medical countermeasures, such as therapeutic drugs and preventive vaccines, animal models that were susceptible to SARS-CoV-2 infection are invaluable ( Zeiss et al, 2021 ; Choudhary et al, 2022 ; Fan et al, 2022 ; Golden et al, 2022 ; Qi and Qin, 2022 ; Rizvi et al, 2022 ; Zhao et al, 2022 ). However, wild-type mice do not support SARS-CoV-2 replication due to the incompatibility of mouse ACE2 with the spike protein of SARS-CoV-2 ( Yang et al, 2007 ; Golden et al, 2020 ; Oladunni et al, 2020 ).…”

Single-cell-resolved interspecies comparison shows a shared inflammatory axis and a dominant neutrophil-endothelial program in severe COVID-19

“…[3][4][5][6][7][8][9] This has been exten-sively described for pulmonary macrophages 10,11 but also for neutrophils, which contribute to disease severity through thrombotic complications caused by NETosis. 12,13 Animal models have been essential in the study of COVID-19 14,15 . Hamsters have been particularly useful as they can be readily infected by the same SARS-CoV-2 variants as humans.…”

Use of a Preclinical Natural Transmission Model to Study Antiviral Effects of a Carbohydrate-Binding Module Therapy against SARS-CoV-2 in Hamsters

“…Syrian hamsters have been widely used for COVID-19 research due to their susceptibility to SARS-CoV-2, and active transmission via aerosol and lung pathology resembling human infection [ 4 ]. Whilst intranasal delivery of the virus has been widely used for SARS-CoV-2 challenge studies [ 5 ], to refine the Syrian hamster model we have developed a natural transmission caging system, where donor animals challenged with SARS-CoV-2 are housed in a central cage and two adjacent cages house recipient animals, with airflow drawing across from the donor animal cage to the side cages [ 6 ]. Other natural transmission models for SARS-CoV-2 have also been reported.…”