Viruses (May 2022)
Exposure Route Influences Disease Severity in the COVID-19 Cynomolgus Macaque Model
- Sandra L. Bixler,
- 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,
- Margaret L. M. Pitt
Affiliations
- Sandra L. Bixler
- Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA
- Christopher P. Stefan
- Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Alexandra N. Jay
- Veterinary Medicine Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Franco D. Rossi
- Veterinary Medicine Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Keersten M. Ricks
- Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Charles J. Shoemaker
- Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Alicia M. Moreau
- Pathology Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Xiankun Zeng
- Pathology Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Jay W. Hooper
- Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA
- David N. Dyer
- Veterinary Medicine Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Ondraya M. Frick
- Veterinary Medicine Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Jeffrey W. Koehler
- Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Brian J. Kearney
- Core Laboratory Services, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Nina DiPinto
- Pathology Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Jun Liu
- Pathology Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Samantha D. Tostenson
- Core Laboratory Services, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Tamara L. Clements
- Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Jeffrey M. Smith
- Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA
- Joshua A. Johnson
- Core Laboratory Services, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Kerry L. Berrier
- Veterinary Medicine Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Heather L. Esham
- Veterinary Medicine Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Korey L. Delp
- Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Susan R. Coyne
- Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Holly A. Bloomfield
- Core Laboratory Services, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Paul A. Kuehnert
- Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Kristen Akers
- Core Laboratory Services, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Kathleen M. Gibson
- Core Laboratory Services, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Timothy D. Minogue
- Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Aysegul Nalca
- Core Support Directorate, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- Margaret L. M. Pitt
- Office of the Science Advisor, USAMRIID, Fort Detrick, Frederick, MD 21702, USA
- DOI
- https://doi.org/10.3390/v14051013
- Journal volume & issue
-
Vol. 14,
no. 5
p. 1013
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.
Keywords
