PT - JOURNAL ARTICLE AU - Andrew C. Yang AU - Fabian Kern AU - Patricia M. Losada AU - Christina A. Maat AU - Georges Schmartz AU - Tobias Fehlmann AU - Nicholas Schaum AU - Davis P. Lee AU - Kruti Calcuttawala AU - Ryan T. Vest AU - David Gate AU - Daniela Berdnik AU - M. Windy McNerney AU - Divya Channappa AU - Inma Cobos AU - Nicole Ludwig AU - Walter J. Schulz-Schaeffer AU - Andreas Keller AU - Tony Wyss-Coray TI - Broad transcriptional dysregulation of brain and choroid plexus cell types with COVID-19 AID - 10.1101/2020.10.22.349415 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.10.22.349415 4099 - http://biorxiv.org/content/early/2020/10/22/2020.10.22.349415.short 4100 - http://biorxiv.org/content/early/2020/10/22/2020.10.22.349415.full AB - Though SARS-CoV-2 primarily targets the respiratory system, it is increasingly appreciated that patients may suffer neurological symptoms of varied severity1–3. However, an unbiased understanding of the molecular processes across brain cell types that could contribute to these symptoms in COVID-19 patients is still missing. Here, we profile 47,678 droplet-based single-nucleus transcriptomes from the frontal cortex and choroid plexus across 10 non-viral, 4 COVID-19, and 1 influenza patient. We complement transcriptomic data with immunohistochemical staining for the presence of SARS-CoV-2. We find that all major cortex parenchymal and choroid plexus cell types are affected transcriptionally with COVID-19. This arises, in part, from SARS-CoV-2 infection of the cortical brain vasculature, meninges, and choroid plexus, stimulating increased inflammatory signaling into the brain. In parallel, peripheral immune cells infiltrate the brain, microglia activate programs mediating the phagocytosis of live neurons, and astrocytes dysregulate genes involved in neurotransmitter homeostasis. Among neurons, layer 2/3 excitatory neurons—evolutionarily expanded in humans4—show a specific downregulation of genes encoding major SNARE and synaptic vesicle components, predicting compromised synaptic transmission. These perturbations are not observed in terminal influenza. Many COVID-19 gene expression changes are shared with those in chronic brain disorders and reside in genetic variants associated with cognitive function, schizophrenia, and depression. Our findings and public dataset provide a molecular framework and new opportunities to understand COVID-19 related neurological disease.Competing Interest StatementThe authors have declared no competing interest.