Glial activation and increase in cerebral pro-inflammatory cytokine expression in a female animal post-COVID model

Many COVID-19 survivors suffer long-term multi-organ damage leading to some symptoms such as brain fog. Around 25 % of patients report persistent memory loss, concentration difficulties, or other cognitive impairments after a SARS-COV-2 infection. Animal models are crucial for studying the pathophysiology of post-acute COVID-19 sequelae (PASC).

To assess the presence of neuro-inflammatory and glial activation biomarkers in brain tissue after a SARS-CoV-2 infection in an animal model to better understand the pathophysiology of neurocognitive symptoms.

Twelve C57BL/6 female hACE2 mice infected with SARS-CoV-2 Omicron variant (BA.1.17 lineage) and eleven non-infected female mice were included. Different proteins evaluating the innate immune activation in neuro-inflammation (TLR4, MyD88, NF-κB signalling pathway), inflammatory state (interleukins IL-6, IL-18 and IL-1β), and glial neuro-inflammatory response (CD11d, Iba1, GFAP expression) were evaluated from cerebral tissue 28 days after infection.

As compared to non-infected mice, significant higher (p = 0.014) post-COVID expression of IL-18 (suggesting an inflammatory state) and significant higher (p = 0.0473) post-COVID GFAP expression (indicating enhanced astrocytic glia activation in response to the infection) was observed in brain tissue. No significant differences in TLR4 (p = 0.512), MyD88 (p = 0.151), NF-κB p65 (p = 0.712), IL-6 (p = 0.962), IL-1β (p = 0.343), CD11d (p = 0.750), and Iba1 (p = 0.935) expressions were observed.

This study provides evidence on brain neuro-inflammation, highlighting glial activation and IL-18 overexpression after an acute SARS-CoV-2 infection. These findings improve current understanding of post-COVID neuroinflammation and could aid in the design of treatment strategies for persistent neurological sequelae, such as cognitive impairment and mental confusion.