Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19

Genome Medicine

Shengbao Suo¹  Guo-Cheng Yuan²  Nathalie Jette³  Sadhna Ahuja⁴  Mary Fowkes⁴  Nadejda M. Tsankova⁵  John F. Crary⁶  Heather Wargnier⁶  Emma Woodoff-Leith⁶  Dushyant P. Purohit⁷  Behnam Javidfar⁸  Cyril Peter⁸  Schahram Akbarian⁸  André Corvelo⁹  Georgios Voloudakis^1,10  Gabriel E. Hoffman^1,11  Shan Jiang^1,11  John F. Fullard^1,11  Wen Zhang^1,11  Hao-Chih Lee^1,11  Zhiping Shao^1,11  Panos Roussos^1,12 

[1] Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA;Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Neurology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Pathology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Pathology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Pathology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Neuropathology Brain Bank & Research Core, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Pathology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;New York Genome Center, New York, NY, USA;Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, 10029, New York, NY, USA;Mental Illness Research Education and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, 10468, Bronx, NY, USA;

关键词: Gene expression;    Neuroinflammation;    Prefrontal cortex;    Choroid plexus;    SARS-CoV-2;    Microglia;   

DOI  :  10.1186/s13073-021-00933-8

来源: Springer

【 摘 要 】

BackgroundCoronavirus 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.MethodsThree 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.ResultsQuantification 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.ConclusionsDespite 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.

【 授权许可】

CC BY