Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets
Authors and Affiliations
Authors and Affiliations
Young-Il Kim1,2,3,7, Kwang-Min Yu1,2,7, June-Young Koh4,7, Eun-Ha Kim1,2, Se-Mi Kim1,2,3, Eun Ji Kim1,2, Mark Anthony B. Casel1,2, Rare Rollon1, Seung-Gyu Jang1, Min-Suk Song1,2, Su-Jin Park5, Hye Won Jeong1, Eung-Gook Kim1, Ok-Jun Lee1, Yong-Dae Kim1, Younho Choi6, Shin-Ae Lee6, Youn Jung Choi6, Su-Hyung Park4, Jae U. Jung6,* & Young Ki Choi1,2,3,*
1College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea. 2Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Korea. 3Center for Study of Emerging and Re-emerging Viruses, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea. 4Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. 5Division of Life Science, Research Institute of Life Science, Gyeongsang National University, Jinju 52828, Korea. 6Cancer Biology Department and Global Center for Pathogens Research and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 7These authors contributed equally: Young-Il Kim, Kwang-Min Yu, June-Young Koh.
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.