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Age associated susceptibility to SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model
Varun Dwivedi1, Vinay Shivanna2, Shalini Gautam2
1Disease Intervention & Prevention Program, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA.
Insights
Older mice infected with SARS-CoV-2 showed increased lung viral load, mortality, and impaired immune responses, particularly an IgM deficiency. This highlights age-related differences in COVID-19 pathogenesis.
Area of Science:
- Virology
- Immunology
- Gerontology
Background:
- Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, remains a global health concern.
- Clinical data show a higher case fatality rate (CFR) in the elderly.
Purpose of the Study:
- To compare the pathogenesis of SARS-CoV-2 in young and aged K18-hACE2 transgenic mice.
- To understand age-dependent differences in COVID-19 immuno-pathogenesis.
Main Methods:
- Evaluation of morbidity, mortality, viral titers, immune responses (IgM), and lung histopathology.
- Infection of young and aged K18-hACE2 transgenic mice with SARS-CoV-2.
Main Results:
- Aged mice exhibited slightly higher morbidity, mortality, and lung viral replication.
- Older mice showed an impaired IgM response and altered cytokine/chemokine profiles.
- Limited sample size per group was a constraint.
Conclusions:
- SARS-CoV-2 infection impacts aged mice more severely, with impaired immune responses.
- Findings contribute to understanding COVID-19 infectivity and immuno-pathogenesis in the elderly.
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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