Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets

Kim, Young-Il; Yu, Kwang-Min; Koh, June-Young; Kim, Eun-Ha; Kim, Se-Mi; Kim, Eun Ji; Casel, Mark Anthony; Rollon, Rare; Jang, Seung-Gyu; Song, Min-Suk; Park, Su-Jin; Jeong, Hye Won; Kim, Eung-Gook; Lee, Ok-Jun; Choi, Younho; Lee, Shin-Ae; Park, Su-Hyung; Jung, Jae U.; Choi, Young Ki

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 were infected with SARS-CoV-2. Although SARS-CoV-2 was isolated from all ferrets regardless of age, aged ferrets (≥ 3 years old) showed 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. Transcriptome analysis of aged ferret lungs revealed 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.