tetano
Editor, Senior Moderator
Nat Genet
. 2023 Apr 24.
doi: 10.1038/s41588-023-01375-1. Online ahead of print.
Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity
Ryuya Edahiro[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuya Shirai[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Yusuke Takeshima[SUP] 4 [/SUP], Shuhei Sakakibara[SUP] 5 [/SUP], Yuta Yamaguchi[SUP] 2 6 [/SUP], Teruaki Murakami[SUP] 2 6 [/SUP], Takayoshi Morita[SUP] 2 6 [/SUP], Yasuhiro Kato[SUP] 2 6 [/SUP], Yu-Chen Liu[SUP] 7 [/SUP], Daisuke Motooka[SUP] 7 8 9 [/SUP], Yoko Naito[SUP] 8 [/SUP], Ayako Takuwa[SUP] 7 [/SUP], Fuminori Sugihara[SUP] 10 [/SUP], Kentaro Tanaka[SUP] 8 [/SUP], James B Wing[SUP] 11 12 [/SUP], Kyuto Sonehara[SUP] 1 9 13 14 [/SUP], Yoshihiko Tomofuji[SUP] 1 9 13 [/SUP]; Japan COVID-19 Task Force; Ho Namkoong[SUP] 15 [/SUP], Hiromu Tanaka[SUP] 16 [/SUP], Ho Lee[SUP] 16 [/SUP], Koichi Fukunaga[SUP] 16 [/SUP], Haruhiko Hirata[SUP] 2 [/SUP], Yoshito Takeda[SUP] 2 [/SUP], Daisuke Okuzaki[SUP] 7 8 9 12 17 [/SUP], Atsushi Kumanogoh[SUP] 18 19 20 21 22 [/SUP], Yukinori Okada[SUP] 23 24 25 26 27 28 [/SUP]
Collaborators, Affiliations
Abstract
Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell-cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.
. 2023 Apr 24.
doi: 10.1038/s41588-023-01375-1. Online ahead of print.
Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity
Ryuya Edahiro[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuya Shirai[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Yusuke Takeshima[SUP] 4 [/SUP], Shuhei Sakakibara[SUP] 5 [/SUP], Yuta Yamaguchi[SUP] 2 6 [/SUP], Teruaki Murakami[SUP] 2 6 [/SUP], Takayoshi Morita[SUP] 2 6 [/SUP], Yasuhiro Kato[SUP] 2 6 [/SUP], Yu-Chen Liu[SUP] 7 [/SUP], Daisuke Motooka[SUP] 7 8 9 [/SUP], Yoko Naito[SUP] 8 [/SUP], Ayako Takuwa[SUP] 7 [/SUP], Fuminori Sugihara[SUP] 10 [/SUP], Kentaro Tanaka[SUP] 8 [/SUP], James B Wing[SUP] 11 12 [/SUP], Kyuto Sonehara[SUP] 1 9 13 14 [/SUP], Yoshihiko Tomofuji[SUP] 1 9 13 [/SUP]; Japan COVID-19 Task Force; Ho Namkoong[SUP] 15 [/SUP], Hiromu Tanaka[SUP] 16 [/SUP], Ho Lee[SUP] 16 [/SUP], Koichi Fukunaga[SUP] 16 [/SUP], Haruhiko Hirata[SUP] 2 [/SUP], Yoshito Takeda[SUP] 2 [/SUP], Daisuke Okuzaki[SUP] 7 8 9 12 17 [/SUP], Atsushi Kumanogoh[SUP] 18 19 20 21 22 [/SUP], Yukinori Okada[SUP] 23 24 25 26 27 28 [/SUP]
Collaborators, Affiliations
- PMID: 37095364
- DOI: 10.1038/s41588-023-01375-1
Abstract
Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell-cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.