Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19

Francisco J. Salguero, Andrew D. White, Gillian S. Slack, Susan A. Fotheringham, Kevin R. Bewley, Karen E. Gooch, Stephanie Longet, Holly E. Humphries, Robert J. Watson, Laura Hunter, Kathryn A. Ryan, Yper Hall, Laura Sibley, Charlotte Sarfas, Lauren Allen, Marilyn Aram, Emily Brunt, Phillip Brown, Karen R. Buttigieg, Breeze E. Cavell, Rebecca Cobb, Naomi S. Coombes, Alistair Darby, Owen Daykin-Pont, Michael J. Elmore, Isabel Garcia-Dorival, Konstantinos Gkolfinos, Kerry J. Godwin, Jade Gouriet, Rachel Halkerston, Debbie J. Harris, Thomas Hender, Catherine M. K. Ho, Chelsea L. Kennard, Daniel Knott, Stephanie Leung, Vanessa Lucas, Adam Mabbutt, Alexandra L. Morrison, Charlotte Nelson, Didier Ngabo, Jemma Paterson, Elizabeth J. Penn, Steve Pullan, Irene Taylor, Tom Tipton, Stephen Thomas, Julia A. Tree, Carrie Turner, Edith Vamos, Nadina Wand, Nathan R. Wiblin, Sue Charlton, Xiaofeng Dong, Bassam Hallis, Geoffrey Pearson, Emma L. Rayner, Andrew G. Nicholson, Simon G. Funnell, Julian A. Hiscox, Mike J. Dennis, Fergus V. Gleeson, Sally Sharpe and Miles W. Carroll ()
Additional contact information
Francisco J. Salguero: National Infection Service, Public Health England (PHE)
Andrew D. White: National Infection Service, Public Health England (PHE)
Gillian S. Slack: National Infection Service, Public Health England (PHE)
Susan A. Fotheringham: National Infection Service, Public Health England (PHE)
Kevin R. Bewley: National Infection Service, Public Health England (PHE)
Karen E. Gooch: National Infection Service, Public Health England (PHE)
Stephanie Longet: National Infection Service, Public Health England (PHE)
Holly E. Humphries: National Infection Service, Public Health England (PHE)
Robert J. Watson: National Infection Service, Public Health England (PHE)
Laura Hunter: National Infection Service, Public Health England (PHE)
Kathryn A. Ryan: National Infection Service, Public Health England (PHE)
Yper Hall: National Infection Service, Public Health England (PHE)
Laura Sibley: National Infection Service, Public Health England (PHE)
Charlotte Sarfas: National Infection Service, Public Health England (PHE)
Lauren Allen: National Infection Service, Public Health England (PHE)
Marilyn Aram: National Infection Service, Public Health England (PHE)
Emily Brunt: National Infection Service, Public Health England (PHE)
Phillip Brown: National Infection Service, Public Health England (PHE)
Karen R. Buttigieg: National Infection Service, Public Health England (PHE)
Breeze E. Cavell: National Infection Service, Public Health England (PHE)
Rebecca Cobb: National Infection Service, Public Health England (PHE)
Naomi S. Coombes: National Infection Service, Public Health England (PHE)
Alistair Darby: University of Liverpool
Owen Daykin-Pont: National Infection Service, Public Health England (PHE)
Michael J. Elmore: National Infection Service, Public Health England (PHE)
Isabel Garcia-Dorival: University of Liverpool
Konstantinos Gkolfinos: National Infection Service, Public Health England (PHE)
Kerry J. Godwin: National Infection Service, Public Health England (PHE)
Jade Gouriet: National Infection Service, Public Health England (PHE)
Rachel Halkerston: National Infection Service, Public Health England (PHE)
Debbie J. Harris: National Infection Service, Public Health England (PHE)
Thomas Hender: National Infection Service, Public Health England (PHE)
Catherine M. K. Ho: National Infection Service, Public Health England (PHE)
Chelsea L. Kennard: National Infection Service, Public Health England (PHE)
Daniel Knott: National Infection Service, Public Health England (PHE)
Stephanie Leung: National Infection Service, Public Health England (PHE)
Vanessa Lucas: National Infection Service, Public Health England (PHE)
Adam Mabbutt: National Infection Service, Public Health England (PHE)
Alexandra L. Morrison: National Infection Service, Public Health England (PHE)
Charlotte Nelson: University of Liverpool
Didier Ngabo: National Infection Service, Public Health England (PHE)
Jemma Paterson: National Infection Service, Public Health England (PHE)
Elizabeth J. Penn: National Infection Service, Public Health England (PHE)
Steve Pullan: National Infection Service, Public Health England (PHE)
Irene Taylor: National Infection Service, Public Health England (PHE)
Tom Tipton: National Infection Service, Public Health England (PHE)
Stephen Thomas: National Infection Service, Public Health England (PHE)
Julia A. Tree: National Infection Service, Public Health England (PHE)
Carrie Turner: National Infection Service, Public Health England (PHE)
Edith Vamos: University of Liverpool
Nadina Wand: National Infection Service, Public Health England (PHE)
Nathan R. Wiblin: National Infection Service, Public Health England (PHE)
Sue Charlton: National Infection Service, Public Health England (PHE)
Xiaofeng Dong: University of Liverpool
Bassam Hallis: National Infection Service, Public Health England (PHE)
Geoffrey Pearson: National Infection Service, Public Health England (PHE)
Emma L. Rayner: National Infection Service, Public Health England (PHE)
Andrew G. Nicholson: Royal Brompton and Harefield NHS Foundation Trust, and National Heart and Lung Institute, Imperial College
Simon G. Funnell: National Infection Service, Public Health England (PHE)
Julian A. Hiscox: University of Liverpool
Mike J. Dennis: National Infection Service, Public Health England (PHE)
Fergus V. Gleeson: Oxford University
Sally Sharpe: National Infection Service, Public Health England (PHE)
Miles W. Carroll: National Infection Service, Public Health England (PHE)

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory samples revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.

Date: 2021
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DOI: 10.1038/s41467-021-21389-9

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