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| Status |
Public on Jun 16, 2021 |
| Title |
The landscape of human brain immune response in patients with severe COVID-19 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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. 3 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 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. 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 cortical microglia associated with a range of biological processes, including cellular activation, mobility and phagocytosis. Despite the absence of detectable SARS-CoV-2 in the brain at time of death, the findings suggest significant and persistent neuroinflammation in patients with acute COVID-19.
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| Overall design |
Single-nucleus transcriptome analysis of human brain tissue from patients with coronavirus disease 2019 amd controls
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| Contributor(s) |
Fullard JF, Lee H, Roussos P |
| Citation(s) |
34281603 |
| Submission date |
Jan 09, 2021 |
| Last update date |
Jul 21, 2021 |
| Contact name |
Panos Roussos |
| E-mail(s) |
panagiotis.roussos@mssm.edu
|
| Phone |
212-824-8982
|
| Organization name |
Icahn School of Medicine at Mount Sinai
|
| Department |
Psychiatry
|
| Street address |
1470 Madison Ave
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA690931 |
| SRA |
SRP301022 |
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