Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem
Abstract Following infection with SARS-CoV-2, patients may experience with one or more symptoms that appear or persist over time. Neurological symptoms associated with long COVID include anxiety, depression, and memory impairment. However, the exact underlying mechanisms are not yet fully understood...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62048-7 |
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| _version_ | 1849342500127375360 |
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| author | Anthony Coleon Florence Larrous Lauriane Kergoat Magali Tichit David Hardy Thomas Obadia Etienne Kornobis Hervé Bourhy Guilherme Dias de Melo |
| author_facet | Anthony Coleon Florence Larrous Lauriane Kergoat Magali Tichit David Hardy Thomas Obadia Etienne Kornobis Hervé Bourhy Guilherme Dias de Melo |
| author_sort | Anthony Coleon |
| collection | DOAJ |
| description | Abstract Following infection with SARS-CoV-2, patients may experience with one or more symptoms that appear or persist over time. Neurological symptoms associated with long COVID include anxiety, depression, and memory impairment. However, the exact underlying mechanisms are not yet fully understood. Using golden hamsters as a model, we provide further evidence that SARS-CoV-2 is neuroinvasive and can persistently infect the brain, as viral RNA and replicative virus are detected in the brainstem 80 days after the initial infection. Infected hamsters exhibit a neurodegenerative signature in the brainstem, characterized by overexpression of innate immunity genes, and altered expression of genes involved in the dopaminergic and glutamatergic synapses, in energy metabolism, and in proteostasis. These infected animals exhibit persistent depression-like behavior, impaired short-term memory, and late-onset signs of anxiety. Finally, we provide evidence that viral and immunometabolic mechanisms coexist in the brainstem of SARS-CoV-2-infected hamsters, contributing to the manifestation of neuropsychiatric and cognitive symptoms. |
| format | Article |
| id | doaj-art-0b1a539d3e994fb6aa11f600d85846a8 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0b1a539d3e994fb6aa11f600d85846a82025-08-20T03:43:22ZengNature PortfolioNature Communications2041-17232025-07-0116111710.1038/s41467-025-62048-7Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstemAnthony Coleon0Florence Larrous1Lauriane Kergoat2Magali Tichit3David Hardy4Thomas Obadia5Etienne Kornobis6Hervé Bourhy7Guilherme Dias de Melo8Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitInstitut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitInstitut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitInstitut Pasteur, Université Paris Cité, Histopathology Core FacilityInstitut Pasteur, Université Paris Cité, Histopathology Core FacilityInstitut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics HubInstitut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics HubInstitut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitInstitut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitAbstract Following infection with SARS-CoV-2, patients may experience with one or more symptoms that appear or persist over time. Neurological symptoms associated with long COVID include anxiety, depression, and memory impairment. However, the exact underlying mechanisms are not yet fully understood. Using golden hamsters as a model, we provide further evidence that SARS-CoV-2 is neuroinvasive and can persistently infect the brain, as viral RNA and replicative virus are detected in the brainstem 80 days after the initial infection. Infected hamsters exhibit a neurodegenerative signature in the brainstem, characterized by overexpression of innate immunity genes, and altered expression of genes involved in the dopaminergic and glutamatergic synapses, in energy metabolism, and in proteostasis. These infected animals exhibit persistent depression-like behavior, impaired short-term memory, and late-onset signs of anxiety. Finally, we provide evidence that viral and immunometabolic mechanisms coexist in the brainstem of SARS-CoV-2-infected hamsters, contributing to the manifestation of neuropsychiatric and cognitive symptoms.https://doi.org/10.1038/s41467-025-62048-7 |
| spellingShingle | Anthony Coleon Florence Larrous Lauriane Kergoat Magali Tichit David Hardy Thomas Obadia Etienne Kornobis Hervé Bourhy Guilherme Dias de Melo Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem Nature Communications |
| title | Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem |
| title_full | Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem |
| title_fullStr | Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem |
| title_full_unstemmed | Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem |
| title_short | Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem |
| title_sort | hamsters with long covid present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem |
| url | https://doi.org/10.1038/s41467-025-62048-7 |
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