Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets
Young‐Il Kim, Kwang-Min Yu, June‐Young Koh, Eun-Ha Kim, Se‐Mi Kim, Eun Ji Kim, Mark Anthony B. Casel, Rare Rollon, Seung‐Gyu Jang, Min‐Suk Song, Su‐Jin Park, Hye Won Jeong, Eung‐Gook Kim, Ok-Jun Lee, Yong‐Dae Kim, Younho Choi, Shin-Ae Lee, Youn Jung Choi, Su‐Hyung Park, Jae U. Jung, Young Ki Choi, Jae U. Jung, Young Ki Choi, Young Ki Choi
Abstract
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.