Cross-sectional case-control studies (Blue)
Though SARS-CoV-2 primarily targets the respiratory system, patients and survivors can suffer neurological symptoms. Yet, an unbiased understanding of the cellular and molecular processes affected in the brains of COVID-19 patients is still missing. In this article the authors profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control (including 1 terminal influenza) and 8 COVID-19 patients. While a systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, the authors observe broad cellular perturbations which predict that choroid plexus barrier cells sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. The authors discover COVID-19 disease-associated microglia and astrocyte subpopulations that share features with pathological cell states reported in human neurodegenerative disease. Synaptic signaling of upper-layer excitatory neurons—evolutionarily expanded in humans and linked to cognitive function—are preferentially affected in COVID-19. Across cell types, COVID-19 perturbations overlap with those in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia, and depression. The authors concluded that their findings and public dataset provide a molecular framework to understand COVID-19 related neurological disease observed now and which may emerge later.
Yang, A. C. et al. Dysregulation of brain and choroid plexus cell types in severe COVID-19. Nature