Establishment of an African green monkey model for COVID-19 and protection against reinfection

Woolsey, Courtney; Borisevich, Viktoriya; Prasad, Abhishek N.; Agans, Krystle N.; Deer, Daniel J.; Dobias, Natalie S.; Heymann, John C.; Foster, Stephanie L.; Levine, Corri B.; Medina, Liana; Melody, Kevin; Geisbert, Joan B.; Fenton, Karla A.; Geisbert, Thomas W.; Cross, Robert W.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen vaccines and treatments. We show African green monkeys (AGMs) support robust SARS-CoV-2 replication and develop pronounced respiratory disease, which may more accurately reflect human COVID-19 cases than other nonhuman primate species. SARS-CoV-2 was detected in mucosal samples, including rectal swabs, as late as 15 days post-exposure. Marked inflammation and coagulopathy in blood and tissues were prominent features. Transcriptome analysis demonstrated stimulation of interferon and interleukin 6 pathways in bronchoalveolar lavage samples and repression of natural killer cell- and T cell-associated transcripts in peripheral blood. Despite a slight waning in antibody titers after primary challenge, enhanced antibody and cellular responses contributed to rapid clearance after re-challenge with an identical strain. These data support the utility of AGM for studying COVID-19 pathogenesis and testing medical countermeasures.