ACTIVating Resources for the COVID-19 Pandemic: In vivo Models for Vaccines and Therapeutics

Hewitt, Judith A.; Lutz, Cathleen; Florence, William C.; Pitt, M. Louise M.; Rao, Srinivas; Rappaport, Jay; Haigwood, Nancy L.

The Preclinical Working Group of Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership spearheaded by the National Institutes of Health, was charged with identifying, prioritizing, and communicating SARS-CoV-2 preclinical resources. Reviewing SARS-CoV-2 animal model data facilitates standardization and harmonization and informs knowledge gaps and prioritization of limited resources. To date, mouse, hamster, ferret, guinea pig, and non-human primates have been investigated. Several species are permissive for SARS-CoV-2 replication, often exhibiting mild disease with resolution, reflecting most human COVID-19 cases. More severe disease develops in a few models, some associated with advanced age, a risk factor for human disease. This review provides a snapshot that recommends the suitability of models for testing vaccines and therapeutics, which may evolve as our understanding of COVID-19 disease biology improves. COVID-19 is a complex disease and individual models recapitulate certain aspects of disease; therefore, the coordination and assessment of animal models is imperative.