Journal
NATURE
Volume 595, Issue 7868, Pages 565-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03710-0
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Funding
- NOMIS Foundation
- National Institute on Aging [T32-AG0047126, 1RF1AG059694]
- Nan Fung Life Sciences
- Bertarelli Brain Rejuvenation Sequencing Cluster (an initiative of the Stanford Wu Tsai Neurosciences Institute)
- Stanford Alzheimer's Disease Research Center [P30 AG066515]
- Siebel Scholarship
- State of Saarland
- Rolf M. Schwiete Stiftung
- Saarland University
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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.
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.
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