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

Viruses

Kristen Akers¹  Brian J. Kearney¹  Joshua A. Johnson¹  Kathleen M. Gibson¹  Samantha D. Tostenson¹  Holly A. Bloomfield¹  Aysegul Nalca²  Timothy D. Minogue³  Paul A. Kuehnert³  Susan R. Coyne³  Christopher P. Stefan³  Jeffrey W. Koehler³  Keersten M. Ricks³  Tamara L. Clements³  Korey L. Delp³  Charles J. Shoemaker³  Margaret L. M. Pitt⁴  Nina DiPinto⁵  Jun Liu⁵  Alicia M. Moreau⁵  Xiankun Zeng⁵  Kerry L. Berrier⁶  Ondraya M. Frick⁶  Heather L. Esham⁶  Franco D. Rossi⁶  David N. Dyer⁶  Alexandra N. Jay⁶  Sandra L. Bixler⁷  Jeffrey M. Smith⁷  Jay W. Hooper⁷ 

[1] Core Laboratory Services, USAMRIID, Fort Detrick, Frederick, MD 21702, USA;Core Support Directorate, USAMRIID, Fort Detrick, Frederick, MD 21702, USA;Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA;Office of the Science Advisor, USAMRIID, Fort Detrick, Frederick, MD 21702, USA;Pathology Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA;Veterinary Medicine Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA;Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA;

关键词: SARS-CoV-2;    COVID;    nonhuman primate;    aerosol;    pathology;    animal models;   

DOI  :  10.3390/v14051013

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown