Coleon Anthony, Larrous Florence, Kergoat Lauriane, Tichit Magali, Hardy David, Obadia Thomas, Kornobis Etienne, Bourhy Hervé, de Melo Guilherme Dias
Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, Paris, France.
Institut Pasteur, Université Paris Cité, Histopathology Core Facility, Paris, France.
Nat Commun. 2025 Jul 22;16(1):6714. doi: 10.1038/s41467-025-62048-7.
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.
感染新型冠状病毒（SARS-CoV-2）后，患者可能会出现一种或多种随时间出现或持续存在的症状。与长期新冠相关的神经症状包括焦虑、抑郁和记忆障碍。然而，确切的潜在机制尚未完全明确。我们以金黄地鼠为模型，提供了进一步的证据，证明SARS-CoV-2具有神经侵袭性，并且能够持续感染大脑，因为在初次感染80天后，在脑干中检测到了病毒RNA和复制型病毒。受感染的地鼠在脑干中呈现出神经退行性特征，其特点是先天免疫基因过度表达，以及参与多巴胺能和谷氨酸能突触、能量代谢和蛋白质稳态的基因表达发生改变。这些受感染的动物表现出持续的抑郁样行为、短期记忆受损以及迟发性焦虑症状。最后，我们提供证据表明，病毒和免疫代谢机制在SARS-CoV-2感染的地鼠脑干中共存，导致神经精神和认知症状的表现。
