Early Surge in Brain GFAP Distribution in Female Hamsters With Mild Peripheral COVID-19

Area of Science:

• Neuroscience
• Immunology
• Virology

Background:

• Mild to moderate COVID-19 is linked to neurological symptoms.
• Proposed mechanisms include cytokine entry via a compromised blood-brain barrier or direct brain infection.
• Neuroinflammation may impair synaptic transmission and cause cognitive dysfunction.

Purpose of the Study:

• To investigate astrogliosis, a key indicator of neuroinflammation, in the context of mild to moderate COVID-19.
• To examine sex differences in astrogliosis.
• To determine the spatiotemporal profile of astrogliosis in specific brain regions.

Main Methods:

• A Syrian hamster model of mild to moderate COVID-19 was used.
• Brains were extracted at multiple time points post-inoculation (1, 3, 5, 7, 31 days).
• Immunolabeling with astrocyte (GFAP, SOX9) and neuron (NEUN) markers was performed, followed by quantitative analysis using a novel pipeline.

Main Results:

• A significant, transient increase in GFAP distribution was observed in the cortex of female hamsters at 3 days post-inoculation.
• Increased GFAP-positive process complexity, indicating altered astrocyte morphology, was also noted in the female cortex at 3 days.
• No changes in astrocyte or neuron numbers were found, and no alterations were observed in male hamsters at any time point.

Conclusions:

• This study provides the first spatiotemporal insights into sex differences in astrogliosis following mild to moderate COVID-19.
• Astrocytes exhibit sex-specific reactivity in response to SARS-CoV-2 infection.
• The findings contribute to understanding the neurological sequelae of COVID-19.