Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19.
Publication/Presentation Date
7-19-2021
Abstract
BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with neurological and neuropsychiatric illness in many individuals. We sought to further our understanding of the relationship between brain tropism, neuro-inflammation, and host immune response in acute COVID-19 cases.
METHODS: Three brain regions (dorsolateral prefrontal cortex, medulla oblongata, and choroid plexus) from 5 patients with severe COVID-19 and 4 controls were examined. The presence of the virus was assessed by western blot against viral spike protein, as well as viral transcriptome analysis covering > 99% of SARS-CoV-2 genome and all potential serotypes. Droplet-based single-nucleus RNA sequencing (snRNA-seq) was performed in the same samples to examine the impact of COVID-19 on transcription in individual cells of the brain.
RESULTS: Quantification of viral spike S1 protein and viral transcripts did not detect SARS-CoV-2 in the postmortem brain tissue. However, analysis of 68,557 single-nucleus transcriptomes from three distinct regions of the brain identified an increased proportion of stromal cells, monocytes, and macrophages in the choroid plexus of COVID-19 patients. Furthermore, differential gene expression, pseudo-temporal trajectory, and gene regulatory network analyses revealed transcriptional changes in the cortical microglia associated with a range of biological processes, including cellular activation, mobility, and phagocytosis.
CONCLUSIONS: Despite the absence of detectable SARS-CoV-2 in the brain at the time of death, the findings suggest significant and persistent neuroinflammation in patients with acute COVID-19.
Volume
13
Issue
1
First Page
118
Last Page
118
ISSN
1756-994X
Published In/Presented At
Fullard, J. F., Lee, H. C., Voloudakis, G., Suo, S., Javidfar, B., Shao, Z., Peter, C., Zhang, W., Jiang, S., Corvelo, A., Wargnier, H., Woodoff-Leith, E., Purohit, D. P., Ahuja, S., Tsankova, N. M., Jette, N., Hoffman, G. E., Akbarian, S., Fowkes, M., Crary, J. F., … Roussos, P. (2021). Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19. Genome medicine, 13(1), 118. https://doi.org/10.1186/s13073-021-00933-8
Disciplines
Medicine and Health Sciences
PubMedID
34281603
Department(s)
Medical Education
Document Type
Article