Vaccination prevents IL-1β-mediated cognitive deficits after COVID-19

Area of Science:

• Neuroscience
• Immunology
• Infectious Diseases

Background:

• Post-acute cognitive sequelae, including memory dysfunction, affect a significant portion of SARS-CoV-2 patients.
• The mechanisms underlying COVID-19-associated cognitive impairment and the protective role of vaccination remain unclear.
• Elevated Interleukin-1 (IL-1) levels in the hippocampus are observed in COVID-19 patients, suggesting a role in neuroinflammation.

Approach:

• SARS-CoV-2 beta variant intranasal infection in C57BL/6J mice induced central nervous system (CNS) monocyte infiltration and microglial activation.
• Investigated the impact of SARS-CoV-2 and H1N1 influenza virus on brain IL-1β levels and hippocampal neurogenesis.
• Assessed the effect of adenoviral vectored Spike protein vaccination on cognitive deficits following breakthrough SARS-CoV-2 infection.

Key Points:

• SARS-CoV-2 infection, unlike H1N1 influenza, elevated brain IL-1β levels and caused persistent IL-1 receptor 1 (IL-1R1)-mediated loss of hippocampal neurogenesis.
• This neurogenesis loss in the hippocampus promoted post-acute cognitive deficits in the murine model.
• Breakthrough SARS-CoV-2 infection in vaccinated mice prevented IL-1β production, neurogenesis loss, and memory deficits.

Conclusions:

• Interleukin-1 beta (IL-1β) is identified as a key mediator of SARS-CoV-2-induced cognitive impairment.
• Vaccination with adenoviral vectored Spike protein offers protection against SARS-CoV-2-induced memory deficits.
• This study presents a novel murine model for investigating COVID-19-associated cognitive dysfunction and the efficacy of vaccination.