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

Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE

Original Publication: New York, NY : Nature America Inc. c2000-

Interleukin-1beta*/metabolism ; Interleukin-1beta*/immunology ; COVID-19*/immunology ; COVID-19*/prevention & control ; SARS-CoV-2*/immunology ; Hippocampus*/immunology ; Hippocampus*/metabolism ; Mice, Inbred C57BL* ; Memory Disorders*/immunology ; Neurogenesis*/immunology; Animals ; Mice ; Vaccination ; Spike Glycoprotein, Coronavirus/immunology ; COVID-19 Vaccines/immunology ; Male ; Humans ; Microglia/immunology ; Microglia/metabolism ; Disease Models, Animal ; Receptors, Interleukin-1 Type I/metabolism ; Receptors, Interleukin-1 Type I/genetics ; Monocytes/immunology ; Monocytes/metabolism ; Female

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 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 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

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R35NS122310 U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS); R01NS104471 U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS); R01AI139251 U.S. Department of Health & Human Services | National Institutes of Health (NIH); F32NS128065 Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID); F32 NS128065 United States NS NINDS NIH HHS

0 (Interleukin-1beta)
0 (Spike Glycoprotein, Coronavirus)
0 (COVID-19 Vaccines)
0 (spike protein, SARS-CoV-2)
0 (IL1B protein, mouse)
0 (Receptors, Interleukin-1 Type I)

SARS-CoV-2 variants

Date Created: 20240620 Date Completed: 20240704 Latest Revision: 20240810

20240812

10.1038/s41590-024-01868-z

38902519