Dysregulation of brain and choroid plexus cell types in severe COVID-19
- PMID: 34153974
- PMCID: PMC8400927
- DOI: 10.1038/s41586-021-03710-0
Dysregulation of brain and choroid plexus cell types in severe COVID-19
Erratum in
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Publisher Correction: Dysregulation of brain and choroid plexus cell types in severe COVID-19.Nature. 2021 Oct;598(7882):E4. doi: 10.1038/s41586-021-04080-3. Nature. 2021. PMID: 34625744 Free PMC article. No abstract available.
Abstract
Although SARS-CoV-2 primarily targets the respiratory system, patients with and survivors of COVID-19 can suffer neurological symptoms1-3. However, an unbiased understanding of the cellular and molecular processes that are affected in the brains of patients with COVID-19 is missing. Here we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control individuals (including 1 patient with terminal influenza) and 8 patients with COVID-19. Although our systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations indicating that barrier cells of the choroid plexus sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. We discover microglia and astrocyte subpopulations associated with COVID-19 that share features with pathological cell states that have previously been reported in human neurodegenerative disease4-6. Synaptic signalling of upper-layer excitatory neurons-which are evolutionarily expanded in humans7 and linked to cognitive function8-is preferentially affected in COVID-19. Across cell types, perturbations associated with COVID-19 overlap with those found in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia and depression. Our findings and public dataset provide a molecular framework to understand current observations of COVID-19-related neurological disease, and any such disease that may emerge at a later date.
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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Comment in
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Single-cell transcriptomics reveals neuroinflammation in severe COVID-19.Nat Rev Neurol. 2021 Aug;17(8):461. doi: 10.1038/s41582-021-00536-2. Nat Rev Neurol. 2021. PMID: 34234324 Free PMC article. No abstract available.
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