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Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity.
Edahiro, Ryuya; Shirai, Yuya; Takeshima, Yusuke; Sakakibara, Shuhei; Yamaguchi, Yuta; Murakami, Teruaki; Morita, Takayoshi; Kato, Yasuhiro; Liu, Yu-Chen; Motooka, Daisuke; Naito, Yoko; Takuwa, Ayako; Sugihara, Fuminori; Tanaka, Kentaro; Wing, James B; Sonehara, Kyuto; Tomofuji, Yoshihiko; Namkoong, Ho; Tanaka, Hiromu; Lee, Ho; Fukunaga, Koichi; Hirata, Haruhiko; Takeda, Yoshito; Okuzaki, Daisuke; Kumanogoh, Atsushi; Okada, Yukinori.
  • Edahiro R; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Shirai Y; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Takeshima Y; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Sakakibara S; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Yamaguchi Y; Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
  • Murakami T; Laboratory of Experimental Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
  • Morita T; Laboratory of Immune Regulation, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Kato Y; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Liu YC; Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
  • Motooka D; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Naito Y; Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
  • Takuwa A; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Sugihara F; Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
  • Tanaka K; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Wing JB; Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
  • Sonehara K; Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Tomofuji Y; Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Namkoong H; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.
  • Tanaka H; Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Lee H; Laboratory of Human Immunology (Single Cell Genomics), WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Fukunaga K; Core Instrumentation Facility, Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Hirata H; Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Takeda Y; Laboratory of Human Immunology (Single Cell Immunology), Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Okuzaki D; Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Japan.
  • Kumanogoh A; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Okada Y; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.
Nat Genet ; 55(5): 753-767, 2023 05.
Article in English | MEDLINE | ID: covidwho-2294568
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Leukocytes, Mononuclear / COVID-19 Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: Nat Genet Journal subject: Genetics, Medical Year: 2023 Document Type: Article Affiliation country: S41588-023-01375-1

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Leukocytes, Mononuclear / COVID-19 Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: Nat Genet Journal subject: Genetics, Medical Year: 2023 Document Type: Article Affiliation country: S41588-023-01375-1