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Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem

Author

Listed:
  • Anthony Coleon

    (Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit)

  • Florence Larrous

    (Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit)

  • Lauriane Kergoat

    (Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit)

  • Magali Tichit

    (Université Paris Cité, Histopathology Core Facility)

  • David Hardy

    (Université Paris Cité, Histopathology Core Facility)

  • Thomas Obadia

    (Université Paris Cité, Bioinformatics and Biostatistics Hub
    Université Paris Cité, G5 Infectious Diseases Epidemiology and Analytics)

  • Etienne Kornobis

    (Université Paris Cité, Bioinformatics and Biostatistics Hub
    Université Paris Cité, Plate-forme Technologique Biomics)

  • Hervé Bourhy

    (Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit)

  • Guilherme Dias de Melo

    (Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit)

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.

Suggested Citation

  • Anthony Coleon & Florence Larrous & Lauriane Kergoat & Magali Tichit & David Hardy & Thomas Obadia & Etienne Kornobis & Hervé Bourhy & Guilherme Dias de Melo, 2025. "Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62048-7
    DOI: 10.1038/s41467-025-62048-7
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    References listed on IDEAS

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