tetano
Editor, Senior Moderator
Genome Med
. 2021 Jul 19;13(1):118.
doi: 10.1186/s13073-021-00933-8.
Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19
John F Fullard[SUP] #[/SUP][SUP] 1 2 3 4 5 [/SUP], Hao-Chih Lee[SUP] #[/SUP][SUP] 1 2 3 4 5 [/SUP], Georgios Voloudakis[SUP] 1 2 5 [/SUP], Shengbao Suo[SUP] 6 [/SUP], Behnam Javidfar[SUP] 2 5 [/SUP], Zhiping Shao[SUP] 1 2 3 4 5 [/SUP], Cyril Peter[SUP] 2 5 [/SUP], Wen Zhang[SUP] 1 2 3 4 5 [/SUP], Shan Jiang[SUP] 1 2 3 4 5 [/SUP], André Corvelo[SUP] 7 [/SUP], Heather Wargnier[SUP] 8 9 10 [/SUP], Emma Woodoff-Leith[SUP] 8 9 10 [/SUP], Dushyant P Purohit[SUP] 5 8 [/SUP], Sadhna Ahuja[SUP] 8 [/SUP], Nadejda M Tsankova[SUP] 8 9 [/SUP], Nathalie Jette[SUP] 11 12 [/SUP], Gabriel E Hoffman[SUP] 1 2 3 4 5 [/SUP], Schahram Akbarian[SUP] 2 5 [/SUP], Mary Fowkes[SUP] 8 [/SUP], John F Crary[SUP] 8 9 10 [/SUP], Guo-Cheng Yuan[SUP] 4 13 [/SUP], Panos Roussos[SUP] 14 15 16 17 18 19 [/SUP]
Affiliations
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: Choroid plexus; Gene expression; Microglia; Neuroinflammation; Prefrontal cortex; SARS-CoV-2.
. 2021 Jul 19;13(1):118.
doi: 10.1186/s13073-021-00933-8.
Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19
John F Fullard[SUP] #[/SUP][SUP] 1 2 3 4 5 [/SUP], Hao-Chih Lee[SUP] #[/SUP][SUP] 1 2 3 4 5 [/SUP], Georgios Voloudakis[SUP] 1 2 5 [/SUP], Shengbao Suo[SUP] 6 [/SUP], Behnam Javidfar[SUP] 2 5 [/SUP], Zhiping Shao[SUP] 1 2 3 4 5 [/SUP], Cyril Peter[SUP] 2 5 [/SUP], Wen Zhang[SUP] 1 2 3 4 5 [/SUP], Shan Jiang[SUP] 1 2 3 4 5 [/SUP], André Corvelo[SUP] 7 [/SUP], Heather Wargnier[SUP] 8 9 10 [/SUP], Emma Woodoff-Leith[SUP] 8 9 10 [/SUP], Dushyant P Purohit[SUP] 5 8 [/SUP], Sadhna Ahuja[SUP] 8 [/SUP], Nadejda M Tsankova[SUP] 8 9 [/SUP], Nathalie Jette[SUP] 11 12 [/SUP], Gabriel E Hoffman[SUP] 1 2 3 4 5 [/SUP], Schahram Akbarian[SUP] 2 5 [/SUP], Mary Fowkes[SUP] 8 [/SUP], John F Crary[SUP] 8 9 10 [/SUP], Guo-Cheng Yuan[SUP] 4 13 [/SUP], Panos Roussos[SUP] 14 15 16 17 18 19 [/SUP]
Affiliations
- PMID: 34281603
- DOI: 10.1186/s13073-021-00933-8
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: Choroid plexus; Gene expression; Microglia; Neuroinflammation; Prefrontal cortex; SARS-CoV-2.