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

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.

SARS-CoV-2 spike S1 subunit protein-mediated increase of beta-secretase 1 (BACE1) impairs human brain vessel cells

“…Exogenous stimuli inducing persistent endothelial cell damage aggravate aging. A recent study showed increased aging-related pathogenic molecules in rodents infected with SARS-CoV-2 [ 5 ]. Here, we investigated whether exposure to the SARS-CoV-2 spike S1 subunit protein affects cellular senescence, a key phenomenon of aging.…”

“…A recent study demonstrates that cognitive impairment due to long COVID is equivalent to accelerated aging, the equivalent of 20 years [ 3 , 4 ]. Age-associated pathogenesis has been observed in SARS-CoV-2 infected animals [ 5 ] and COVID-19 patients [ 6 ]. Clinical studies show that approximately 30–50% of COVID-19 patients experience long COVID symptoms, which are common with increasing age and female sex [ 7 ].…”

Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells

“…These findings have been echoed in multiple single site studies where, both within and outside of households, the infection rate of the ancestral SARS-CoV-2 among children <10 years old is significantly lower than that of adults [ 3 , 4 ]. Reduced SARS-CoV-2 infection and transmission is also observed in juvenile ferrets compared to their older counterparts [ 5 ].…”

The Reassessed Potential of SARS-CoV-2 Attenuation for COVID-19 Vaccine Development—A Systematic Review

“…Non-human primates (NHPs), such as rhesus macaques or cynomolgus macaques, were not used in the reviewed studies but would have provided the most human-like model of attenuated SARS-CoV-2 infection [ 141 , 142 , 143 ]. Ferrets are not very susceptible to SARS-CoV-2 infection, although some conflicting reports exist [ 144 , 145 , 146 ] and are probably most useful in studying the transmission of the vaccine virus [ 146 , 147 ].…”