Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease.
Summary
The authors generated human ACE2 transgenic pigs that support productive SARS-CoV-2 infection and exhibit hallmark clinical signs and lung immunopathology mirroring severe human COVID-19. Viral replication was detected in upper and lower airways through day 7 post-infection.
Key Findings
- Human ACE2 transgenic pigs supported SARS-CoV-2 replication in nasal turbinates, trachea, and lungs up to day 7 post-infection.
- Animals developed clinical signs (fever, cough, respiratory distress) consistent with COVID-19.
- Lung histopathology showed immunopathologic features similar to fatal human COVID-19.
Clinical Implications
While preclinical, this model may accelerate evaluation of respiratory antivirals, vaccines, and immunomodulators with pathophysiologic fidelity, informing dose, delivery route, and safety before human trials.
Why It Matters
This establishes the first robust large-animal COVID-19 model in pigs, enabling mechanistic studies, vaccine/therapeutic testing, and translational insights not feasible in rodents.
Limitations
- Short follow-up limited to 7 days post-infection
- Transgenic overexpression may not fully recapitulate endogenous ACE2 distribution
Future Directions
Extend longitudinal studies, assess variant-specific pathogenesis, evaluate vaccines/therapeutics, and refine ACE2 expression patterns to mimic human physiology.
Study Information
- Study Type
- Basic/Mechanistic research
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical mechanistic animal model without human comparative outcomes
- Study Design
- OTHER