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Dysregulation of brain and choroid plexus cell types in severe COVID-19 #MMPMID34153974
Yang AC; Kern F; Losada PM; Agam MR; Maat CA; Schmartz GP; Fehlmann T; Stein JA; Schaum N; Lee DP; Calcuttawala K; Vest RT; Berdnik D; Lu N; Hahn O; Gate D; McNerney MW; Channappa D; Cobos I; Ludwig N; Schulz-Schaeffer WJ; Keller A; Wyss-Coray T
Nature 2021[Jul]; 595 (7868): 565-571 PMID34153974show ga
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.