Dysregulation of brain and choroid plexus cell types in severe COVID-19

Although SARS-CoV-2 primarily targets the respiratory system, patients with and survivors of COVID-19 can suffer neurological symptoms(1-3). 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 disease(4-6). Synaptic signalling of upper-layer excitatory neurons-which are evolutionarily expanded in humans(7) and linked to cognitive function(8)-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.

Automated summary

This study found that patients with COVID-19 exhibited widespread cellular perturbations in the brain, including the relay of peripheral inflammation into the brain by choroid plexus barrier cells and infiltration of peripheral T cells. Additionally, COVID-19 affected synaptic signaling of upper-layer excitatory neurons linked to cognitive function.