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

Abigail Vanderheiden; Jeremy Hill; Xiaoping Jiang; Ben Deppen; Gayan Bamunuarachchi; Nadia Soudani; Astha Joshi; Matthew D Cain; Adrianus C M Boon; Robyn S Klein

doi:10.21203/rs.3.rs-3353171/v1

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

Res Sq [Preprint]. 2023 Sep 15:rs.3.rs-3353171. doi: 10.21203/rs.3.rs-3353171/v1.

Authors

Abigail Vanderheiden^{1

2}, Jeremy Hill^{1

2}, Xiaoping Jiang^{1

2}, Ben Deppen^{1

2}, Gayan Bamunuarachchi², Nadia Soudani², Astha Joshi², Matthew D Cain², Adrianus C M Boon^{2

3}, Robyn S Klein^{1

2

3

4}

Affiliations

¹ Center for Neuroimmunology and Neuroinfectious Diseases, Washington University School of Medicine, St. Louis, MO, USA.
² Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
⁴ Department of Neurosciences, Washington University School of Medicine, St. Louis, MO, USA.

Abstract

Up to 25% of SARS-CoV-2 patients exhibit post-acute cognitive sequelae. Although millions of cases of COVID-19-mediated memory dysfunction are accumulating worldwide, the underlying mechanisms and how vaccination lowers risk are unknown. Interleukin-1, a key component of innate immune defense against SARS-CoV-2 infection, is elevated in the hippocampi of COVID-19 patients. Here we show that intranasal infection of C57BL/6J mice with SARS-CoV-2 beta variant, leads to CNS infiltration of Ly6C^hi monocytes and microglial activation. Accordingly, SARS-CoV-2, but not H1N1 influenza virus, increases levels of brain IL-1β and induces persistent IL-1R1-mediated loss of hippocampal neurogenesis, which promotes post-acute cognitive deficits. Breakthrough infection after vaccination with a low dose of adenoviral vectored Spike protein prevents hippocampal production of IL-1β during breakthrough SARS-CoV-2 infection, loss of neurogenesis, and subsequent memory deficits. Our study identifies IL-1β as one potential mechanism driving SARS-CoV-2-induced cognitive impairment in a new murine model that is prevented by vaccination.

Publication types

Preprint

Abstract

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