critical data on pathogenesis, efficacy, and correlates of protection. Following infection with
SARS-CoV-2, Syrian hamsters, K18-ACE2 mice, and some aged African green monkeys (AGMs)
develop moderate to severe pulmonary disease. Rhesus macaques (M. mulatta), cynomolgous
macaques (M. fascicularis), and other macaques do not generally experience severe disease but
do support robust viral replication and develop mild to moderate pulmonary disease with
multiple inflammatory biomarkers, and are thus considered excellent models for testing
therapeutics, vaccines and monoclonal antibodies. Notably, decades of research have led to an
excellent understanding of the pathogenesis and immunity of coronaviruses and other
infectious diseases in rhesus macaques. Scientists who are interested in performing
experiments in NHP models are encouraged to read several review articles that have been
published recently, in order to understand the potential and limitations of different models.
The science continues to move rapidly as discoveries are made, so it is also wise to consult with
contacts who can steer the specific study that an individual investigator may have in mind.
Some of the recent reviews are:
Muñoz-Fontela, C., Dowling, W.E., Funnell, S.G.P. et al. Animal models for COVID-
19. Nature 586, 509–515 (2020). https://doi.org/10.1038/s41586-020-2787-6
Johansen, M.D., Irving, A., Montagutelli, X., Tate, M.D., Rudloff, I., Nold, M.F., Hansbro,
N.G., Kim, R.Y., Donovan, C., Liu, G., Faiz, A., Short, K.R., Lyons, J.G., McCaughan, G.W.,
Gorrell, M.D., Cole, A., Moreno, C., Couteur, D., Hesselson, D., Triccas, J., Neely, G.G.,
Gamble, J.R., Simpson, S.J., Saunders, B.M., Oliver, B.G., Britton, W.J., Wark, P.A., Nold-
Petry, C.A., Hansbro, P.M. Animal and translational models of SARS-CoV-2 infection
and COVID-19. Mucosal Immunol. 2020 Nov;13(6):877-891. doi: 10.1038/s41385-020-
00340-z. Epub 2020 Aug 20.PMID: 32820248
Hewitt, J.A., Lutz, C., Florence, W.C., Pitt, M.L.M., Rao, S., Rappaport, J., Haigwood, N.L.
ACTIVating Resources for the COVID-19 Pandemic: In Vivo Models for Vaccines and
Therapeutics. Cell Host Microbe. 2020 Nov 11;28(5):646-659. doi:
10.1016/j.chom.2020.09.016. Epub 2020 Oct 1.PMID: 33152279
The most important consideration in planning to use NHP models is whether the answer can be
obtained with another species such as mouse, ferret or hamster. In many cases, small animal
studies will be required prior to advancing to NHP, and some questions may not be addressible
in NHP models.
With support from the Foundation for the National Institutes of Health (FNIH), Accelerating
COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Preclinical working group has
developed an Open Data Portal where up-to-date summaries for both small and large animal
models are available. This portal provides information about the extent of the interventions,
disease manifestations, and pathology evaluated.