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

Geroscience. 2024 Jun;46(3):2901-2913. doi: 10.1007/s11357-024-01102-6. Epub 2024 Feb 22.

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.

Keywords: Aging; COVID-19; Cytokine storm; K18-hACE2 transgenic mouse; SARS-CoV-2 infection.

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme 2* / genetics
  • Animals
  • COVID-19* / immunology
  • COVID-19* / metabolism
  • Cytokines
  • Disease Models, Animal
  • Humans
  • Immunoglobulin M
  • Mice
  • Mice, Transgenic
  • SARS-CoV-2* / pathogenicity

Substances

  • Cytokines
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Immunoglobulin M