Journal Article

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

Schmartz, Georges P., Agam, Maayan R., Wyss-Coray, Tony, Hahn, Oliver, Gate, David, Cobos, Inma, Lu, Nannan, Stein, Julian A., Vest, Ryan T., Kern, Fabian, Fehlmann, Tobias, Schaum, Nicholas, Channappa, Divya, Ludwig, Nicole, Calcuttawala, Kruti, Lee, Davis P., McNerney, M. Windy, Maat, Christina A., Losada, Patricia M., Schulz-Schaeffer, Walter J., Keller, Andreas, Yang, Andrew C., Berdnik, Daniela

2021

Overview

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. Single-nucleus transcriptomes of frontal cortex and choroid plexus samples from patients with COVID-19 reveal pathological cell states that are similar to those associated with human neurodegenerative diseases and chronic brain disorders.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 13/51 / 38/91 / 631/1647/664/1257 / 631/250/254 / 631/250/371 / 631/326/596/4130 / 631/337/2019 / 631/378/87 / Aged / Aged, 80 and over / Alzheimer's disease / Antibodies / Astrocytes - pathology / Brain / Brain - metabolism / Brain - pathology / Brain - physiopathology / Brain - virology / Brain diseases / Cell Nucleus - genetics / Choroid / Choroid plexus / Choroid Plexus - metabolism / Choroid Plexus - pathology / Choroid Plexus - physiopathology / Choroid Plexus - virology / Cognition / Cognitive ability / Coronaviruses / Cortex (frontal) / COVID-19 / COVID-19 - diagnosis / COVID-19 - genetics / COVID-19 - pathology / COVID-19 - physiopathology / Female / Genes / Genetic diversity / Genetic variance / Health aspects / Humanities and Social Sciences / Humans / Infections / Inflammation / Inflammation - virology / Influenza / Lymphocytes / Lymphocytes T / Male / Mental disorders / Microglia / Microglia - pathology / Middle Aged / multidisciplinary / Neurological diseases / Neurons - pathology / Parenchyma / Patients / Perturbation / Respiratory system / SARS-CoV-2 - growth & development / SARS-CoV-2 - pathogenicity / Schizophrenia / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Single-Cell Analysis / Subpopulations / Synaptic transmission / Transcriptome / Transcriptomes / Viral infections / Virus Replication