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Volume 14
Issue 5
10.3390/v14051013
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Article

Exposure Route Influences Disease Severity in the COVID-19 Cynomolgus Macaque Model

by
Sandra L. Bixler
1,*,
Christopher P. Stefan
2,
Alexandra N. Jay
3,
Franco D. Rossi
3,
Keersten M. Ricks
2,
Charles J. Shoemaker
2,
Alicia M. Moreau
4,
Xiankun Zeng
4,
Jay W. Hooper
1,
David N. Dyer
3,
Ondraya M. Frick
3,
Jeffrey W. Koehler
2,
Brian J. Kearney
5,
Nina DiPinto
4,†,
Jun Liu
4,
Samantha D. Tostenson
5,
Tamara L. Clements
2,
Jeffrey M. Smith
1,
Joshua A. Johnson
5,‡,
Kerry L. Berrier
3,
Heather L. Esham
3,
Korey L. Delp
2,
Susan R. Coyne
2,
Holly A. Bloomfield
5,
Paul A. Kuehnert
2,
Kristen Akers
5,§,
Kathleen M. Gibson
5,‖,
Timothy D. Minogue
2,
Aysegul Nalca
6 and
Margaret L. M. Pitt
7,*add Show full author list remove Hide full author list
1
Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA
2
Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
3
Veterinary Medicine Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
4
Pathology Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
5
Core Laboratory Services, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
6
Core Support Directorate, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
7
Office of the Science Advisor, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
*
Authors to whom correspondence should be addressed.
†
Current address: Antech Diagnostics, Fountain Valley, CA 92708, USA.
‡
Current address: Texcell-North America, Frederick, MD 21703, USA.
§
Current address: Meritus Medical Laboratory, Hagerstown, MD 21742, USA.
‖
Current address: Logistics Management Institute, Alexandria, VA 22310, USA.
Academic Editor: F. Javier Salguero
Viruses 2022, 14(5), 1013; https://doi.org/10.3390/v14051013
Received: 30 March 2022 / Revised: 29 April 2022 / Accepted: 5 May 2022 / Published: 10 May 2022
(This article belongs to the Special Issue SARS-CoV-2 and Animal Models)
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Abstract

The emergence of SARS-CoV-2 and the subsequent pandemic has highlighted the need for animal models that faithfully replicate the salient features of COVID-19 disease in humans. These models are necessary for the rapid selection, testing, and evaluation of potential medical countermeasures. Here, we performed a direct comparison of two distinct routes of SARS-CoV-2 exposure—combined intratracheal/intranasal and small particle aerosol—in two nonhuman primate species, rhesus and cynomolgus macaques. While all four experimental groups displayed very few outward clinical signs, evidence of mild to moderate respiratory disease was present on radiographs and at necropsy. Cynomolgus macaques exposed via the aerosol route also developed the most consistent fever responses and had the most severe respiratory disease and pathology. This study demonstrates that while all four models produced suitable representations of mild COVID-like illness, aerosol exposure of cynomolgus macaques to SARS-CoV-2 produced the most severe disease, which may provide additional clinical endpoints for evaluating therapeutics and vaccines. View Full-Text
Keywords: SARS-CoV-2; COVID; nonhuman primate; aerosol; pathology; animal models SARS-CoV-2; COVID; nonhuman primate; aerosol; pathology; animal models
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MDPI and ACS Style

Bixler, S.L.; Stefan, C.P.; Jay, A.N.; Rossi, F.D.; Ricks, K.M.; Shoemaker, C.J.; Moreau, A.M.; Zeng, X.; Hooper, J.W.; Dyer, D.N.; Frick, O.M.; Koehler, J.W.; Kearney, B.J.; DiPinto, N.; Liu, J.; Tostenson, S.D.; Clements, T.L.; Smith, J.M.; Johnson, J.A.; Berrier, K.L.; Esham, H.L.; Delp, K.L.; Coyne, S.R.; Bloomfield, H.A.; Kuehnert, P.A.; Akers, K.; Gibson, K.M.; Minogue, T.D.; Nalca, A.; Pitt, M.L.M. Exposure Route Influences Disease Severity in the COVID-19 Cynomolgus Macaque Model. Viruses 2022, 14, 1013. https://doi.org/10.3390/v14051013

AMA Style

Bixler SL, Stefan CP, Jay AN, Rossi FD, Ricks KM, Shoemaker CJ, Moreau AM, Zeng X, Hooper JW, Dyer DN, Frick OM, Koehler JW, Kearney BJ, DiPinto N, Liu J, Tostenson SD, Clements TL, Smith JM, Johnson JA, Berrier KL, Esham HL, Delp KL, Coyne SR, Bloomfield HA, Kuehnert PA, Akers K, Gibson KM, Minogue TD, Nalca A, Pitt MLM. Exposure Route Influences Disease Severity in the COVID-19 Cynomolgus Macaque Model. Viruses. 2022; 14(5):1013. https://doi.org/10.3390/v14051013

Chicago/Turabian Style

Bixler, Sandra L., Christopher P. Stefan, Alexandra N. Jay, Franco D. Rossi, Keersten M. Ricks, Charles J. Shoemaker, Alicia M. Moreau, Xiankun Zeng, Jay W. Hooper, David N. Dyer, Ondraya M. Frick, Jeffrey W. Koehler, Brian J. Kearney, Nina DiPinto, Jun Liu, Samantha D. Tostenson, Tamara L. Clements, Jeffrey M. Smith, Joshua A. Johnson, Kerry L. Berrier, Heather L. Esham, Korey L. Delp, Susan R. Coyne, Holly A. Bloomfield, Paul A. Kuehnert, Kristen Akers, Kathleen M. Gibson, Timothy D. Minogue, Aysegul Nalca, and Margaret L.M. Pitt. 2022. "Exposure Route Influences Disease Severity in the COVID-19 Cynomolgus Macaque Model" Viruses 14, no. 5: 1013. https://doi.org/10.3390/v14051013

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