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Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in
Anthony Coleon1, Florence Larrous1, Lauriane Kergoat1
1Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, Paris, France.
Nature Communications
|July 22, 2025
Summary
SARS-CoV-2 infection can persistently affect the brain, leading to long COVID neurological symptoms. This study in hamsters reveals brainstem neurodegeneration, immune gene changes, and lasting depression and memory issues.
Area of Science:
- Neuroscience
- Infectious Diseases
- Genetics
Background:
- Long COVID is associated with persistent neurological symptoms like anxiety, depression, and memory impairment.
- The precise mechanisms underlying these long COVID neurological effects remain unclear.
Purpose of the Study:
- To investigate the neuroinvasive potential of SARS-CoV-2.
- To elucidate the mechanisms behind SARS-CoV-2-induced neurological and behavioral deficits in a mammalian model.
Main Methods:
- Utilized golden hamsters as a model for SARS-CoV-2 infection.
- Detected viral RNA and replicative virus in the brainstem.
- Analyzed gene expression related to immunity, synaptic function, metabolism, and proteostasis.
- Assessed behavioral changes including depression-like behavior, memory, and anxiety.
Main Results:
- SARS-CoV-2 was detected in the hamster brainstem 80 days post-infection, confirming neuroinvasion and persistence.
- Infected hamsters showed a neurodegenerative signature with upregulated innate immunity genes.
- Alterations in genes involved in dopaminergic/glutamatergic synapses, energy metabolism, and proteostasis were observed.
- Persistent depression-like behavior, impaired short-term memory, and late-onset anxiety were evident.
Conclusions:
- SARS-CoV-2 infection leads to persistent brainstem infection and neurodegeneration in hamsters.
- Combined viral and immunometabolic mechanisms in the brainstem contribute to long COVID neuropsychiatric and cognitive symptoms.
