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

 

Andrew C. Yang, 

Fabian Kern, 

Patricia M. Losada, 

Maayan R. Agam, 

Christina A. Maat, 

Georges P. Schmartz, 

Tobias Fehlmann, 

Julian A. Stein, 

Nicholas Schaum, 

Davis P. Lee, 

Kruti Calcuttawala, 

Ryan T. Vest, 

Daniela Berdnik, 

Nannan Lu, 

Oliver Hahn,

David Gate,

M. Windy McNerney, 

Divya Channappa, 

Inma Cobos, 

Nicole Ludwig, 

Walter J. Schulz-Schaeffer, 

Andreas Keller & 

Tony Wyss-Coray 

• DOI: https://doi.org/10.1038/s41586-021-03710-0

• PDF: https://www.nature.com/articles/s41586-021-03710-0_reference.pdf

• Abstract

  Though SARS-CoV-2 primarily targets the respiratory system, patients and survivors can suffer neurological symptoms1–3. Yet, an unbiased understanding of the cellular and molecular processes affected in the brains of COVID-19 patients is still missing. Here, we 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, we 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. We discover COVID-19 disease-associated microglia and astrocyte subpopulations that share features with pathological cell states reported in human neurodegenerative disease4–6. Synaptic signaling of upper-layer excitatory neurons—evolutionarily expanded in humans7 and linked to cognitive function8—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. Our findings and public dataset provide a molecular framework to understand COVID-19 related neurological disease observed now and which may emerge later.

• https://www.nature.com/articles/s41586-021-03710-0