| Autor: |
Zumbrun EE; Division of Virology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Zak SE; Division of Virology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Lee ED; Division of Pathology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Bowling PA; Division of Veterinary Medicine, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Ruiz SI; Division of Bacteriology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Zeng X; Division of Pathology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Koehler JW; Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Delp KL; Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Bakken RR; Division of Virology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Hentschel SS; Division of Virology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Bloomfield HA; Division of Pathology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Ricks KM; Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Clements TL; Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Babka AM; Division of Pathology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Dye JM; Division of Virology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA., Herbert AS; Division of Virology, United States Army Medical Research Institute of Infectious Disease, Frederick, MD 21702, USA. |
| Abstrakt: |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the worldwide COVID-19 pandemic. Animal models are extremely helpful for testing vaccines and therapeutics and for dissecting the viral and host factors that contribute to disease severity and transmissibility. Here, we report the assessment and comparison of intranasal and small particle (~3 µm) aerosol SARS-CoV-2 exposure in ferrets. The primary endpoints for analysis were clinical signs of disease, recovery of the virus in the upper respiratory tract, and the severity of damage within the respiratory tract. This work demonstrated that ferrets were productively infected with SARS-CoV-2 following either intranasal or small particle aerosol exposure. SARS-CoV-2 infection of ferrets resulted in an asymptomatic disease course following either intranasal or small particle aerosol exposure, with no clinical signs, significant weight loss, or fever. In both aerosol and intranasal ferret models, SARS-CoV-2 replication, viral genomes, and viral antigens were detected within the upper respiratory tract, with little to no viral material detected in the lungs. The ferrets exhibited a specific IgG immune response to the SARS-CoV-2 full spike protein. Mild pathological findings included inflammation, necrosis, and edema within nasal turbinates, which correlated to positive immunohistochemical staining for the SARS-CoV-2 virus. Environmental sampling was performed following intranasal exposure of ferrets, and SARS-CoV-2 genomic material was detected on the feeders and nesting areas from days 2-10 post-exposure. We conclude that both intranasal and small particle aerosol ferret models displayed measurable parameters that could be utilized for future studies, including transmission studies and testing SARS-CoV-2 vaccines and therapeutics. |
