Delayed viral clearance and altered inflammatory responses affect severity of SARS-CoV-2 infection in aged mice.
Summary
Comparing young (2 months) and geriatric (15–22 months) K18-ACE2 mice, the study shows that advanced age is associated with delayed SARS-CoV-2 clearance and altered inflammatory responses, contributing to more severe disease. These findings provide mechanistic support for the clinical observation that age drives worse outcomes in viral pneumonia, including ARDS.
Key Findings
- Geriatric K18-ACE2 mice exhibited delayed clearance of SARS-CoV-2 compared with young mice.
- Aged mice showed altered inflammatory responses associated with increased disease severity.
- Age emerged as a mechanistic driver of worse infection outcomes, aligning with human epidemiology.
Clinical Implications
Supports age-tailored strategies: earlier antivirals to enhance viral clearance and immunomodulation to correct maladaptive inflammation in older patients.
Why It Matters
Defines age-related virologic and immunologic mechanisms that can be targeted to mitigate severe COVID-19/ARDS in older hosts.
Limitations
- K18-ACE2 mouse model may not fully recapitulate human disease
- Sample size and full quantitative data are not detailed in the abstract
Future Directions
Dissect molecular pathways linking aging to impaired clearance and dysregulated inflammation; test antivirals/immunomodulators by age; validate in additional models.
Study Information
- Study Type
- Cohort
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical animal study; mechanistic evidence rather than clinical effectiveness
- Study Design
- OTHER