Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19.
Genome Med
; 13(1): 118, 2021 07 19.
Article
in English
| MEDLINE | ID: covidwho-1318291
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Brain
/
Gene Expression Profiling
/
Transcriptome
/
COVID-19
/
Immunity
Type of study:
Observational study
Limits:
Humans
Language:
English
Journal:
Genome Med
Year:
2021
Document Type:
Article
Affiliation country:
S13073-021-00933-8
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