Intranasal infection by SARS-CoV-2 Omicron variants can induce inflammatory brain damage in newly weaned hamsters

Children infected by SARS-CoV-2 Omicron variant may develop neurological complications. To study the pathogenesis in the growing brain, we intranasally challenged newly-weaned or mature hamsters with SARS-CoV-2 Omicron BA.2, BA.5, or Delta variant. Omicron BA.2 and Delta infection produced a signifi...

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Main Authors: Can Li, Wenchen Song, Jasper Fuk-Woo Chan, Yanxia Chen, Feifei Liu, Zhanhong Ye, Alvin Hiu-Chung Lam, Jianpiao Cai, Andrew Chak-Yiu Lee, Bosco Ho-Yin Wong, Hin Chu, David Christopher Lung, Siddharth Sridhar, Honglin Chen, Anna Jin-Xia Zhang, Kwok-Yung Yuen
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2023.2207678
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author Can Li
Wenchen Song
Jasper Fuk-Woo Chan
Yanxia Chen
Feifei Liu
Zhanhong Ye
Alvin Hiu-Chung Lam
Jianpiao Cai
Andrew Chak-Yiu Lee
Bosco Ho-Yin Wong
Hin Chu
David Christopher Lung
Siddharth Sridhar
Honglin Chen
Anna Jin-Xia Zhang
Kwok-Yung Yuen
author_facet Can Li
Wenchen Song
Jasper Fuk-Woo Chan
Yanxia Chen
Feifei Liu
Zhanhong Ye
Alvin Hiu-Chung Lam
Jianpiao Cai
Andrew Chak-Yiu Lee
Bosco Ho-Yin Wong
Hin Chu
David Christopher Lung
Siddharth Sridhar
Honglin Chen
Anna Jin-Xia Zhang
Kwok-Yung Yuen
author_sort Can Li
collection DOAJ
description Children infected by SARS-CoV-2 Omicron variant may develop neurological complications. To study the pathogenesis in the growing brain, we intranasally challenged newly-weaned or mature hamsters with SARS-CoV-2 Omicron BA.2, BA.5, or Delta variant. Omicron BA.2 and Delta infection produced a significantly lower viral load in the lung tissues of newly-weaned than mature hamsters despite comparable histopathological damages. Newly-weaned hamsters had higher brain viral load, significantly increased cerebrospinal fluid concentration of TNF-α and CXCL10 and inflammatory damages including mild meningitis and parenchymal vascular congestion, despite sparse expression of nucleocapsid antigen in brain cells. Furthermore, 63.6% (28/44) of all SARS-CoV-2 infected newly-weaned hamsters showed microgliosis in olfactory bulb (OB), cerebral cortex, and hippocampus. In infected mature hamsters, microgliosis was observed mainly in OB and olfactory cortex of 35.3% (12/34) of their brains. Neuronal degeneration was found in 75% (33/44) of newly-weaned hamsters affecting multiple regions including OB, olfactory cortex, midbrain cortex, and hippocampus, while such changes were mainly observed in the hippocampus of mature hamsters. Importantly, similar brain histopathology was also observed in Omicron BA.5-infected newly-weaned hamsters. Our study suggested that SARS-CoV-2 may affect the brain at a young age. This kind of brain involvement and histological changes are not virus variant or subvariant specific. Incidentally, a moderate amount of eosinophilic infiltration was observed in the mucosa of nasal turbinate and trachea of newly-weaned hamsters infected by Omicron BA.2 and BA.5 but not Delta variant. This histological finding is consistent with the higher incidence of laryngotracheobronchitis in young children infected by the Omicron variant.Summary Intranasal infection of newly-weaned Syrian hamsters by SARS-CoV-2 Omicron variants can lead to brain inflammation and neuron degeneration with detectable low level of viral load and sparse expression of viral nucleoprotein.
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spelling doaj-art-4d5f00bd55bb4494a3ddb5cd60b81c0a2025-08-20T02:24:43ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112110.1080/22221751.2023.2207678Intranasal infection by SARS-CoV-2 Omicron variants can induce inflammatory brain damage in newly weaned hamstersCan Li0Wenchen Song1Jasper Fuk-Woo Chan2Yanxia Chen3Feifei Liu4Zhanhong Ye5Alvin Hiu-Chung Lam6Jianpiao Cai7Andrew Chak-Yiu Lee8Bosco Ho-Yin Wong9Hin Chu10David Christopher Lung11Siddharth Sridhar12Honglin Chen13Anna Jin-Xia Zhang14Kwok-Yung Yuen15State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaDepartment of Pathology, Hong Kong Children’s Hospital, Hong Kong Special Administrative Region, Hongkong, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaState Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of ChinaChildren infected by SARS-CoV-2 Omicron variant may develop neurological complications. To study the pathogenesis in the growing brain, we intranasally challenged newly-weaned or mature hamsters with SARS-CoV-2 Omicron BA.2, BA.5, or Delta variant. Omicron BA.2 and Delta infection produced a significantly lower viral load in the lung tissues of newly-weaned than mature hamsters despite comparable histopathological damages. Newly-weaned hamsters had higher brain viral load, significantly increased cerebrospinal fluid concentration of TNF-α and CXCL10 and inflammatory damages including mild meningitis and parenchymal vascular congestion, despite sparse expression of nucleocapsid antigen in brain cells. Furthermore, 63.6% (28/44) of all SARS-CoV-2 infected newly-weaned hamsters showed microgliosis in olfactory bulb (OB), cerebral cortex, and hippocampus. In infected mature hamsters, microgliosis was observed mainly in OB and olfactory cortex of 35.3% (12/34) of their brains. Neuronal degeneration was found in 75% (33/44) of newly-weaned hamsters affecting multiple regions including OB, olfactory cortex, midbrain cortex, and hippocampus, while such changes were mainly observed in the hippocampus of mature hamsters. Importantly, similar brain histopathology was also observed in Omicron BA.5-infected newly-weaned hamsters. Our study suggested that SARS-CoV-2 may affect the brain at a young age. This kind of brain involvement and histological changes are not virus variant or subvariant specific. Incidentally, a moderate amount of eosinophilic infiltration was observed in the mucosa of nasal turbinate and trachea of newly-weaned hamsters infected by Omicron BA.2 and BA.5 but not Delta variant. This histological finding is consistent with the higher incidence of laryngotracheobronchitis in young children infected by the Omicron variant.Summary Intranasal infection of newly-weaned Syrian hamsters by SARS-CoV-2 Omicron variants can lead to brain inflammation and neuron degeneration with detectable low level of viral load and sparse expression of viral nucleoprotein.https://www.tandfonline.com/doi/10.1080/22221751.2023.2207678CoronavirusCOVID-19SARS-coV-2brainnewly-weaned hamster
spellingShingle Can Li
Wenchen Song
Jasper Fuk-Woo Chan
Yanxia Chen
Feifei Liu
Zhanhong Ye
Alvin Hiu-Chung Lam
Jianpiao Cai
Andrew Chak-Yiu Lee
Bosco Ho-Yin Wong
Hin Chu
David Christopher Lung
Siddharth Sridhar
Honglin Chen
Anna Jin-Xia Zhang
Kwok-Yung Yuen
Intranasal infection by SARS-CoV-2 Omicron variants can induce inflammatory brain damage in newly weaned hamsters
Emerging Microbes and Infections
Coronavirus
COVID-19
SARS-coV-2
brain
newly-weaned hamster
title Intranasal infection by SARS-CoV-2 Omicron variants can induce inflammatory brain damage in newly weaned hamsters
title_full Intranasal infection by SARS-CoV-2 Omicron variants can induce inflammatory brain damage in newly weaned hamsters
title_fullStr Intranasal infection by SARS-CoV-2 Omicron variants can induce inflammatory brain damage in newly weaned hamsters
title_full_unstemmed Intranasal infection by SARS-CoV-2 Omicron variants can induce inflammatory brain damage in newly weaned hamsters
title_short Intranasal infection by SARS-CoV-2 Omicron variants can induce inflammatory brain damage in newly weaned hamsters
title_sort intranasal infection by sars cov 2 omicron variants can induce inflammatory brain damage in newly weaned hamsters
topic Coronavirus
COVID-19
SARS-coV-2
brain
newly-weaned hamster
url https://www.tandfonline.com/doi/10.1080/22221751.2023.2207678
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