Griffin Bryan D, Warner Bryce M, Chan Mable, Valcourt Emelissa, Tailor Nikesh, Banadyga Logan, Leung Anders, He Shihua, Boese Amrit S, Audet Jonathan, Cao Wenguang, Moffat Estella, Garnett Lauren, Tierney Kevin, Tran Kaylie N, Albietz Alixandra, Manguiat Kathy, Soule Geoff, Bello Alexander, Vendramelli Robert, Lin Jessica, Deschambault Yvon, Zhu Wenjun, Wood Heidi, Mubareka Samira, Safronetz David, Strong James E, Embury-Hyatt Carissa, Kobasa Darwyn
Zoonotic Diseases and Special Pathogens Division, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg R3E 3R2, MB, Canada.
Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, 745 Bannatyne Avenue, Winnipeg R3E 0J9, MB, Canada.
iScience. 2021 Dec 17;24(12):103530. doi: 10.1016/j.isci.2021.103530. Epub 2021 Nov 27.
The golden hamster model of SARS-CoV-2 infection recapitulates key characteristics of COVID-19. In this work we examined the influence of the route of exposure, sex, and age on SARS-CoV-2 pathogenesis in hamsters. We report that delivery of SARS-CoV-2 by a low- versus high-volume intranasal or intragastric route results in comparable viral titers in the lung and viral shedding. However, low-volume intranasal exposure results in milder weight loss, whereas intragastric exposure leads to a diminished capacity to regain body weight. Male hamsters, and particularly older male hamsters, display an impaired capacity to recover from illness and delayed viral clearance. These factors were found to influence the nature of the host inflammatory cytokine response but had a minimal effect on the quality and durability of the humoral immune response and susceptibility to re-infection. These data further elucidate key factors that impact pre-clinical challenge studies carried out in the hamster model of COVID-19.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的金黄仓鼠模型概括了2019冠状病毒病（COVID-19）的关键特征。在这项研究中，我们研究了暴露途径、性别和年龄对仓鼠中SARS-CoV-2发病机制的影响。我们报告，通过低容量与高容量鼻内或胃内途径递送SARS-CoV-2会导致肺中病毒滴度和病毒脱落相当。然而，低容量鼻内暴露导致体重减轻较轻，而胃内暴露导致恢复体重的能力减弱。雄性仓鼠，尤其是老年雄性仓鼠，显示出从疾病中恢复的能力受损和病毒清除延迟。发现这些因素会影响宿主炎性细胞因子反应的性质，但对体液免疫反应的质量和持久性以及再次感染的易感性影响最小。这些数据进一步阐明了影响在COVID-19仓鼠模型中进行的临床前挑战研究的关键因素。
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