ArticleCell reports2023
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 160 citations in OpenAlex.
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- Let-7a-5p/SHIP-1 Axis Drives SARS-CoV-2 Spike-1-Induced Microglial Pyroptosis.International journal of molecular sciences · 2026Article
- Neurodegenerative and Cognitive Consequences of Long COVID.International journal of molecular sciences · 2026Review
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- Magnetoencephalography Reveals Neuroprotection of COVID-19 Vaccination in Nonhuman Primates.Vaccines · 2026Article
- Clinical and Inflammatory Predictors of Neurocognitive Decline in Long COVID: A Two-Year Longitudinal Study with Propensity Score Matching.Medicina (Kaunas, Lithuania) · 2026Observational
- Chemical characterization of Jing Guan Fang and its application in alleviating coronavirus envelope protein-induced proinflammatory responsesJournal of traditional and complementary medicine · 2026Article
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- Lung Dysfunction and Systemic Inflammation: A Role for HO-1 and NLRP3 in a COVID-19 Murine Model.Research square · 2026Article
- Extracellular Vesicle-Delivered tRF-His-GTG-1 Reprograms Neutrophil Lipophagy and Triggers Inflammation in COVID-19.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatial multiomics dissects the SARS-CoV-2-induced disruption of cell adhesion and immune dynamics in the human hippocampus.Journal of neuroinflammation · 2026Article
- Herpes simplex virus-1 induces complement-mediated microglial phagocytosis of synapses in murine primary brain cultures and tissues.Cell communication and signaling : CCS · 2026Article
- Long COVID-associated neurological symptoms and brain fog: Understanding the mechanism of neuroinflammation, BBB disruption, diagnostics, and therapeutics.Molecular biology reports · 2026Review
- Viral modulation of synaptic pruning: implications for neuropathology and brain function.Journal of virology · 2026Review
- SARS-CoV-2 Spike Protein Induces Time-Dependent and Brain-Region-Specific Alterations in Ferroptosis Markers: A Preliminary Study in K18-hACE2 Mice.International journal of molecular sciences · 2026Article
- Palmitoylated COX-2Journal of advanced research · 2026Article
- Intranasal S-2P and lentinan formulation confers broad protection against SARS-CoV-2 VOCs via IFN-γ-dominant mechanisms.NPJ vaccines · 2026Article
- From infection to dysfunction: viral triggers and antiviral immune factors in Alzheimer's disease pathology.Frontiers in immunology · 2026Review
- Persistent neurological and behavioral alterations after SARS-CoV-2 infection in an optimized K18-hACE2 mouse model.Frontiers in microbiology · 2026Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or its fragments are released from cells during infection, reaching different tissues, including the CNS, irrespective of the presence of the viral RNA. Here, we demonstrate that brain infusion of Spike protein in mice has a late impact on cognitive function, recapitulating post-COVID-19 syndrome. We also show that neuroinflammation and hippocampal microgliosis mediate Spike-induced memory dysfunction via complement-dependent engulfment of synapses. Genetic or pharmacological blockage of Toll-like receptor 4 (TLR4) signaling protects animals against synapse elimination and memory dysfunction induced by Spike brain infusion. Accordingly, in a cohort of 86 patients who recovered from mild COVID-19, the genotype GG TLR4-2604G>A (rs10759931) is associated with poor cognitive outcome. These results identify TLR4 as a key target to investigate the long-term cognitive dysfunction after COVID-19 infection in humans and rodents.
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