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Published on: April 28, 2019
SARS-CoV-2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID-19 model
Na Yun Lee1, Youn Woo Lee2, Seung-Min Hong3
1Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, 1 Kangwondaehak-Gil, Chuncheon-si, Gangwon-do, 24341, South Korea.
Background:
The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection.
Results:
K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection.
Conclusion:
Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.
Insights
The Omicron variant of SARS-CoV-2 can infect the brain, causing severe illness and lymphoid depletion in mice. This study confirms Omicron brain infection, a previously unreported phenomenon in adult cases and animal models.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Omicron is the dominant SARS-CoV-2 variant, generally causing milder disease than the Wuhan strain.
- While Wuhan strain SARS-CoV-2 brain infection is documented, Omicron's neuroinvasive potential remained unconfirmed in humans and animal models.
Purpose of the Study:
- To investigate Omicron's ability to infect the brain in a susceptible mouse model.
- To compare the neuroinvasive properties of the Omicron variant with the original Wuhan strain of SARS-CoV-2.
Main Methods:
- K18-hACE2 mice were intranasally inoculated with either the Wuhan strain or the Omicron variant of SARS-CoV-2.
- Mice were monitored for 7 days post-infection, assessing body weight loss, and brain and spleen tissues were analyzed via histopathology and immunostaining.
Main Results:
- 40% of Omicron-infected mice experienced over 20% body weight loss, a lethal condition, compared to 100% in Wuhan-infected mice.
- Histopathology and immunostaining confirmed inflammatory responses and severe neuron infection in the brains of Omicron-infected mice.
- Omicron-infected mice with brain involvement exhibited lymphoid depletion and apoptosis in the spleen.
Conclusions:
- Omicron variant SARS-CoV-2 infection can lead to lethal conditions, including encephalopathy, in K18-hACE2 mice.
- This study provides the first evidence of Omicron-induced brain infection and associated lymphoid depletion in a mouse model of COVID-19.
