COVID's Lingering Brain Impact: Memory & Mood Damage

After contracting SARS-CoV-2 (the virus that causes COVID-19), patients can experience one or more symptoms that appear or persist over time. Among these are COVID-related neurological symptoms, including anxiety, depression, and memory impairments. However, the exact underlying mechanisms for these long-term effects are not yet fully understood.

Providing new insights, on July 22, 2025, Anthony Coleon and his team at Université Paris Cité, France, published a paper in Nature Communications titled, "Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem." In their research, the authors presented evidence that the novel coronavirus is neuroinvasive and can persistently infect the brain, with viral RNA and replicating virus detected in the brainstem up to 80 days after initial infection.

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Overview

Brainstems of SARS-CoV-2-infected hamsters presented with hallmarks of neurodegeneration, evidenced by the upregulation of innate immune genes and transcriptional dysregulation in pathways associated with dopaminergic and glutamatergic synapses, energy metabolism, and protein homeostasis. Concurrently, these hamsters manifested persistent depressive-like behaviors, deficits in short-term memory, and a delayed onset of anxiety phenotypes. This investigation ultimately demonstrated the co-occurrence of viral persistence and perturbed immune-metabolic processes within the brainstem following SARS-CoV-2 infection, underpinning the observed neuropsychiatric and cognitive sequelae.

Findings

Long COVID is a complex condition that can affect various organs and manifest with a range of symptoms following SARS-CoV-2 infection. Since its initial recognition, the definition of Long COVID has evolved, with the latest widely accepted definition proposed by the World Health Organization in February 2025: "This is a condition characterized by a range of symptoms that typically appear within 3 months of the initial SARS-CoV-2 infection and persist for at least 2 months. These symptoms may emerge during the initial illness or appear after recovery. It impacts an individual's ability to perform daily activities, such as work or household chores, and limits social engagement." However, despite a widely accepted definition and various hypotheses and evidence, the precise underlying mechanisms of Long COVID remain incompletely understood, particularly those related to neurological and neuropsychiatric manifestations.

In this study, the authors describe clinical, behavioral, virological, and transcriptomic data from golden hamsters, presenting them as a relevant model for studying Long COVID. The authors provide compelling evidence that the neuropsychiatric symptoms and cognitive impairments associated with Long COVID emerge after the acute infection phase in this model, without the confounding influences of social or somatic factors, or any effects related to post-intensive care syndrome.

In this research, the authors demonstrated that, in a model free from social or somatic influences, golden hamsters infected with SARS-CoV-2 developed persistent and delayed neurological symptoms. The authors describe hamsters as a reliable animal model for Long COVID and provide evidence of the coexistence of viral and neuro-immune-metabolic mechanisms in the brainstem. This coexistence is characterized by neurodegenerative features, including an enhanced innate immune response and impaired neurotransmission and energy metabolism. The model also illustrates the complexity of Long COVID, where clinical presentation varies with time, sex, and viral variant. Finally, this study emphasizes the potential for SARS-CoV-2 to persist in the brain, suggesting that the brainstem may serve as a reservoir for infectious virus during the post-acute phase of COVID-19. Further research should explore the etiology of Long COVID, with studies conducted in humans or valuable and relevant alternative models such as the hamster model described here.

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Reference

1. Coleon, Anthony et al. "Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem." Nature communications vol. 16,1 6714. 22 Jul. 2025, doi:10.1038/s41467-025-62048-7. Distributed under Open Access license CC BY 4.0, without modification.