Vaccination reduces central nervous system IL-1β and memory deficits after COVID-19 in mice

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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Up to 25% of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit postacute cognitive sequelae. Although millions of cases of coronavirus disease 2019 (COVID-19)-mediated memory dysfunction are accumulating worldwide, the underlying mechanisms and how vaccination lowers risk are unknown. Interleukin-1 (IL-1), a key component of innate immune defense against SARS-CoV-2 infection, is elevated in the hippocampi of individuals with COVID-19. Here we show that intranasal infection of C57BL/6J mice with SARS-CoV-2 Beta variant leads to central nervous system infiltration of Ly6Chi 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 postacute cognitive deficits. 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 mouse model that is prevented by vaccination.

Original languageEnglish
Pages (from-to)1158-1171
Number of pages14
JournalNature immunology
Volume25
Issue number7
DOIs
StatePublished - Jul 2024

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