Exploring the Biological Mechanisms of Severe COVID-19 in the Elderly: Insights from an Aged Mouse Model

Definitive parameters or mechanisms underlying the severity of COVID-19 in elderly people remain confused. Thus, this study seeks to elucidate the mechanism behind the increased vulnerability of elderly individuals to severe COVID-19. We employed an aged mouse model with a mouse-adapted SARS-CoV-2 strain to mimic the severe symptoms observed in elderly patients with COVID-19. Comprehensive analyses of the whole lung were performed using transcriptome and proteome sequencing, comparing data from aged and young mice. For transcriptome analysis, bulk RNA sequencing was conducted using an Illumina sequencing platform. Three-week-old and 18-month-old SPF C57BL/6j mice were purchased from Beijing Vital River Laboratory and Jackson Laboratory, respectively. They were then divided into four cohorts, each consisting of nine mice: young and aged groups without infection and young and aged groups with infection. Anesthesia was induced in the mice through intraperitoneal administration of tribromoethanol at a dose of 250 mg/kg body weight. Mice in the infected groups were intranasally inoculated with 2 × 105 plaque-forming units of mouse-adapted SARS-CoV-2 in 30 μL of DMEM per mouse, whereas mice in the uninfected groups were administered 30 μL of DMEM per mouse.Lung samples were collected from three mice in each group at three days post-infection for transcriptomic analyses.