Dysregulation of brain and choroid plexus cell types in severe COVID-19.
Updated September 19, 2023Although 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.
To reference this project, please use the following link:
Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.
Downloaded and exported data is governed by the HCA Data Release Policy and licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). For more information please see our Data Use Agreement.
Analysis Portals
Project Label
Keller-Human-10x3pv3Species
Sample Type
Anatomical Entity
Organ Part
Selected Cell Types
Disease Status (Specimen)
Disease Status (Donor)
Development Stage
Library Construction Method
Nucleic Acid Source
Paired End
falseAnalysis Protocol
analysis_protocol_1File Format
Cell Count Estimate
65.3kDonor Count
22