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

• Published in: Nature immunology Vol. 22; no. 1; pp. 86 - 98
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2021; Nature Publishing Group
• Subjects: 631/326/596/4130; 692/420/254; Alveoli; Animal models; Animals; Antibodies, Viral - immunology; Biological markers; Biomedical and Life Sciences; Biomedicine; Bronchus; Chlorocebus aethiops; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - epidemiology; COVID-19 - immunology; COVID-19 - virology; Disease Models, Animal; Epidemics; Epidemics - prevention & control; Gene expression; Gene Expression - genetics; Gene Expression - immunology; Gene Expression Profiling; Humans; Identification and classification; Immune clearance; Immune response; Immunology; Infectious Diseases; Interferon; Interferons - genetics; Interferons - immunology; Interferons - metabolism; Interleukin 6; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Laboratory animals; Lymphocytes T; Mucosa; Natural killer cells; Pandemics; Pathogenesis; Peripheral blood; Rectum; Reinfection - immunology; Reinfection - virology; Respiratory diseases; SARS-CoV-2 - immunology; SARS-CoV-2 - physiology; Severe acute respiratory syndrome coronavirus 2; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - virology; United States
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-020-00835-8

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 that 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 after 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. Geisbert and colleagues report that African green monkeys infected with the SARS-CoV-2 virus develop disease symptoms that closely resemble those seen in infected humans, making this animal model a useful surrogate to investigate immune responses to coronavirus infection.