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

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...

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Bibliographic Details
Published in:	Viruses Vol. 14; no. 5; p. 1013
Main Authors:	Bixler, Sandra L, Stefan, Christopher P, Jay, Alexandra N, Rossi, Franco D, Ricks, Keersten M, Shoemaker, Charles J, Moreau, Alicia M, Zeng, Xiankun, Hooper, Jay W, Dyer, David N, Frick, Ondraya M, Koehler, Jeffrey W, Kearney, Brian J, DiPinto, Nina, Liu, Jun, Tostenson, Samantha D, Clements, Tamara L, Smith, Jeffrey M, Johnson, Joshua A, Berrier, Kerry L, Esham, Heather L, Delp, Korey L, Coyne, Susan R, Bloomfield, Holly A, Kuehnert, Paul A, Akers, Kristen, Gibson, Kathleen M, Minogue, Timothy D, Nalca, Aysegul, Pitt, Margaret L M
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 10-05-2022 MDPI
Subjects:	aerosol Aerosols Animal models Animals Coronaviruses COVID COVID-19 COVID-19 vaccines Disease Models, Animal Disease transmission Fever Infections Infectious diseases Macaca fascicularis Medical laboratories Medical research Mortality Necropsy nonhuman primate Pathogens pathology Respiratory diseases SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Trachea Viruses United States > US China COVID SARS-CoV-2 animal models nonhuman primate pathology aerosol
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: Meritus Medical Laboratory, Hagerstown, MD 21742, USA. Current address: Antech Diagnostics, Fountain Valley, CA 92708, USA. Current address: Texcell-North America, Frederick, MD 21703, USA. Current address: Logistics Management Institute, Alexandria, VA 22310, USA.
ISSN:	1999-4915 1999-4915
DOI:	10.3390/v14051013