Age associated susceptibility to SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model

K18-hACE2 转基因小鼠模型中年龄相关的 SARS-CoV-2 感染易感性

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作者:Varun Dwivedi, Vinay Shivanna, Shalini Gautam, Jennifer Delgado, Amberlee Hicks, Marco Argonza, Reagan Meredith, Joanne Turner, Luis Martinez-Sobrido, Jordi B Torrelles, Viraj Kulkarni

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still an ongoing global health crisis. Clinical data indicate that the case fatality rate (CFR) is age dependent, with a higher CFR percentage in the elderly population. We compared the pathogenesis of SARS-CoV-2 in young and aged K18-hACE2 transgenic mice. We evaluated morbidity, mortality, viral titers, immune responses, and histopathology in SARS-CoV-2-infected young and old K18-hACE2 transgenic mice. Within the limitation of having a low number of mice per group, our results indicate that SARS-CoV-2 infection resulted in slightly higher morbidity, mortality, and viral replication in the lungs of old mice, which was associated with an impaired IgM response and altered cytokine and chemokine profiles. Results of this study increase our understanding of SARS-CoV-2 infectivity and immuno-pathogenesis in the elderly population.

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