SARS-CoV-2 Aerosol and Intranasal Exposure Models in Ferrets.

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the COVID-19 pandemic.
• Animal models are crucial for evaluating SARS-CoV-2 vaccines, therapeutics, and disease pathogenesis.
• Understanding viral and host factors is key to addressing disease severity and transmission.

Purpose of the Study:

• To compare intranasal versus small particle aerosol SARS-CoV-2 exposure in ferrets.
• To assess clinical signs, viral recovery, and respiratory tract pathology.
• To evaluate the utility of ferret models for future SARS-CoV-2 research.

Main Methods:

• Ferrets were exposed to SARS-CoV-2 via intranasal inoculation or ~3 µm aerosol.
• Primary endpoints included clinical signs, viral shedding from the upper respiratory tract, and histopathology.
• Immune response was assessed via IgG to the SARS-CoV-2 spike protein; environmental sampling was also conducted.

Main Results:

• Both exposure routes led to productive SARS-CoV-2 infection in ferrets.
• Infection was asymptomatic, with no significant clinical signs, weight loss, or fever observed.
• Viral replication, genomes, and antigens were confined to the upper respiratory tract, with minimal lung involvement.
• Mild nasal inflammation, necrosis, and edema were noted, correlating with viral presence.
• A specific IgG immune response to the SARS-CoV-2 spike protein was detected.
• SARS-CoV-2 genomic material was detected in the environment around exposed ferrets.

Conclusions:

• Intranasal and small particle aerosol exposure are viable methods for SARS-CoV-2 infection in ferrets.
• The ferret model exhibits asymptomatic infection with upper respiratory tract viral replication, suitable for studying disease.
• These models provide measurable parameters for future SARS-CoV-2 transmission, vaccine, and therapeutic studies.