SARS‑CoV‑2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID‑19 model
10.1186/s42826-023-00157-4
- Author:
Na Yun LEE
1
;
Youn Woo LEE
;
Seung‑Min HONG
;
Dain ON
;
Gyeong Min YOON
;
See‑He AN
;
Ki Taek NAM
;
Jun‑Young SEO
;
Jeon‑Soo SHIN
;
Yang‑Kyu CHOI
;
Seung Hyun OH
;
Jun‑Won YUN
;
Ho Young LEE
;
Kang‑Seuk CHOI
;
Je Kyung SEONG
;
Jun Won PARK
Author Information
1. Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, 1 Kangwondaehak‑Gil, Chuncheon‑si, Gangwon‑do 24341, South Korea
- Publication Type:SHORT COMMUNICATION
- From:Laboratory Animal Research
2023;39(2):165-171
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
