College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Korea.
Nat Commun. 2022 Jan 10;13(1):21. doi: 10.1038/s41467-021-27717-3.
While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets are infected with SARS-CoV-2. Although SARS-CoV-2 is isolated from all ferrets regardless of age, aged ferrets (≥3 years old) show higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration, and clinical symptoms compared to juvenile (≤6 months) and young adult (1-2 years) groups. Furthermore, direct contact ferrets co-housed with the virus-infected aged group shed more virus than direct-contact ferrets co-housed with virus-infected juvenile or young adult ferrets. Transcriptome analysis of aged ferret lungs reveals strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.
虽然健康人群中 SARS-CoV-2 的血清流行率在不同年龄组之间没有显著差异，但 65 岁及以上人群的 COVID-19 死亡率明显高于年轻人群。为了进一步了解不同年龄患者 COVID-19 表现的差异，我们用 SARS-CoV-2 感染了三组年龄不同的雪貂。尽管无论年龄大小，所有雪貂都能分离到 SARS-CoV-2，但与幼龄（≤6 个月）和青年龄（1-2 岁）组相比，老龄（≥3 岁）雪貂的病毒载量更高，鼻病毒排出时间更长，肺部炎症细胞浸润更严重，临床症状也更严重。此外，与感染病毒的幼龄或青年龄雪貂直接接触的雪貂，其病毒排出量多于与感染病毒的老龄雪貂直接接触的雪貂。老龄雪貂肺部的转录组分析显示，与 I 型干扰素、激活的 T 细胞和 M1 巨噬细胞反应相关的基因集明显富集，与严重 COVID-19 患者的基因表达谱相似。因此，感染 SARS-CoV-2 的老龄雪貂高度重现了有严重症状的 COVID-19 患者，有助于了解 SARS-CoV-2 感染、传播和发病机制与年龄的关系。
