Dogs experimentally infected with the SARS-CoV-2 Delta variant but not showing neurologic or respiratory signs of COVID-19 had evidence of degenerative brain disease on necropsy.
The study, led by Konkuk University researchers in South Korea, was published late last week in Emerging Infectious Diseases. The research team intranasally infected six female beagle dogs with the SARS-CoV-2 Delta virus. The six dogs shared cages with six dogs that weren't experimentally infected. Three uninfected dogs inoculated with a placebo served as controls.
The investigators obtained nose-throat, mouth-throat, fecal swabs, and blood samples from the dogs at 10 different time points. At 10, 12, 14, 38, 40, and 42 days postinfection, one infected and one contact dog were euthanized for necropsy.
Viral DNA found in brain only early in infection
SARS-CoV-2 was detected in a low percentage of nose-throat and mouth-throat swabs in infected and contact dogs. "Remarkably, we found that the viral titers were higher in the nasal and oral mucosa of dogs in the contact group than in those in the infection group," the authors wrote. "That finding could be attributed to the role of the nasal and oral cavities as routes of virus entry for the contact group, resulting in higher replication of the virus at these entry points."
In the early stages of infection, dogs in the contact group showed more severe inflammatory responses in the trachea and bronchioles than were seen in the experimentally infected dogs, which the authors said is consistent with previous studies showing that contact transmission can lead to higher viral concentrations and faster onset of pathologic changes in the upper respiratory tract.
Antibodies were detected in the blood of infected dogs as early as 4 days postinfection. No significant changes in body weight or temperature were observed, and none of the dogs showed neurologic or respiratory signs of COVID-19.
SARS-CoV-2 DNA was detected in the brain at weeks 10, 12, and 14 postinfection only. Infected dogs exhibited abnormal changes to the blood-brain barrier (BBB), primarily at weeks 38, 40, and 42 days. Necropsies at all time points uncovered evidence that the virus had severely damaged BBB cells and crossed the BBB.
Results could be used in translational research
These signs, the researchers said, indicate that SARS-CoV-2 can produce pathologic changes to the BBB's structural and functional integrity. "Such changes may allow entry of peripheral molecules and immune cells into the brain parenchyma during the early infection period," they wrote. "Collectively, the pathologic changes concur with the typical signs of small vessel disease (SVD),"they wrote. SVD is generally caused by the narrowing or blockage of small blood vessels in the brain.
Our study provides evidence that SARS-CoV-2 infection can damage the brain as well as the lungs in dogs at early and later stages of infection, suggesting a high potential for a long-lasting COVID-19–like syndrome to develop in affected dogs.
The results of staining of brain sections demonstrated neuroinflammatory responses in the white matter of infected dogs. Infiltration of immune cells indicating pneumonia led to a thickened lung alveolar septum in infected canines.
"Our study provides evidence that SARS-CoV-2 infection can damage the brain as well as the lungs in dogs at early and later stages of infection, suggesting a high potential for a long-lasting COVID-19–like syndrome to develop in affected dogs," they concluded. "Overall, these data can be used as translational research data to interpret the potential neuropathologic changes that may be observed in humans."