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Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets
Open accessPublished version of a preprint
Abstract
Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.
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“Consistently, the levels of viral spike-protein-specific IgG during early time-points of acute SARS-CoV-2 infection in rhesus macaques are reduced in older macaques compared to young ones, consistent with age crippling the formation of class-switched antibody titers needed to clear the viral infection155.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [155]
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“Consistently, the levels of viral spike-protein-specific IgG during early time-points of acute SARS-CoV-2 infection in rhesus macaques are reduced in older macaques compared to young ones, consistent with age crippling the formation of class-switched antibody titers needed to clear the viral infection155.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [155]
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Metadata
- Authors
- Singh, D. K., Singh, B., Ganatra, S. R., Gazi, M., Cole, J., Thippeshappa, R., Alfson, K. J., Clemmons, E., Gonzalez, O., Escobedo, R., Lee, T.-H., Chatterjee, A., Goez-Gazi, Y., Sharan, R., Gough, M., Alvarez, C., Blakley, A., Ferdin, J., Bartley, C., Staples, H., Parodi, L., Callery, J., Mannino, A., Klaffke, B., Escareno, P., Platt, R. N., Hodara, V., Scordo, J., Gautam, S., Vilanova, A. G., Olmo-Fontanez, A., Schami, A., Oyejide, A., Ajithdoss, D. K., Copin, R., Baum, A., Kyratsous, C., Alvarez, X., Ahmed, M., Rosa, B., Goodroe, A., Dutton, J., Hall-Ursone, S., Frost, P. A., Voges, A. K., Ross, C. N., Sayers, K., Chen, C., Hallam, C., Khader, S. A., Mitreva, M., Anderson, T. J. C., Martinez-Sobrido, L., Patterson, J. L., Turner, J., Torrelles, J. B., Dick, E. J., Brasky, K., Schlesinger, L. S., Giavedoni, L. D., Carrion, R., & Kaushal, D.
- Affiliations
- Texas Biomedical Research Institute (US)
- Regeneron (United States) (US)
- Washington University in St. Louis (US)
- Corresponding author
- Giavedoni, Luis D.
- Carrion, Ricardo
- Kaushal, Deepak
- ORCID
- Singh, Dhiraj Kumar
- Singh, Bindu
- Ganatra, Shashank R.
- Thippeshappa, Rajesh
- Alfson, Kendra J.
- Clemmons, Elizabeth
- Escobedo, Ruby
- Lee, Tae-Hyung
- Chatterjee, Ayan
- Sharan, Riti
- Bartley, Carmen
- Staples, Hilary
- Mannino, Amanda
- Platt, Roy N.
- Hodara, Vida
- Scordo, Julia
- Gautam, Shalini
- Vilanova, Andreu G.
- Schami, Alyssa
- Oyejide, Adelekan
- Ajithdoss, Dharani K.
- Copin, Richard
- Baum, Alina
- Kyratsous, Christos
- Alvarez, Xavier
- Ahmed, Mushtaq
- Rosa, Bruce
- Goodroe, Anna
- Dutton, John
- Hall-Ursone, Shannan
- Voges, Andra K.
- Ross, Corinna N.
- Sayers, Ken
- Chen, Christopher
- Hallam, Cory
- Khader, Shabaana A.
- Mitreva, Makedonka
- Anderson, Timothy J. C.
- Patterson, Jean L.
- Turner, Joanne
- Torrelles, Jordi B.
- Dick, Edward J.
- Schlesinger, Larry S.
- Giavedoni, Luis D.
- Carrion, Ricardo
- Kaushal, Deepak
- Venue
- Nature Microbiology
- Published
- 2020-12-18
- Volume
- 6
- Issue
- 1
- Pages
- 73-86
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC7890948
- OpenAlex
- W3116593921
- Cited by
- 209
- References
- 45
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 22 · 2023: 29 · 2022: 51 · 2021: 71 · 2020: 11
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-01-18)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R01AI134236)
- U.S. Department of Health & Human Services | NIH | NIH Office of the Director (P51OD011133)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, nonhuman primate model, rhesus monkeys, baboons, marmoset, age-related immune response, pneumonitis, lung inflammation, viral RNA shedding, type I interferon response, T cell memory, IgG antibody response, cell-mediated immunity
- MeSH terms
- COVID-19, SARS-CoV-2, Animals, Antibodies, Viral, Bronchoalveolar Lavage Fluid, Callithrix, Female, Humans, Immunoglobulin G, Immunity, Cellular, Inflammation, Lung, Macaca mulatta, Male, Monkey Diseases, Papio, Virus Shedding, Bronchoalveolar Lavage, Viral Load, Myeloid Cells, Adaptive Immunity
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