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The Genetic Risk for COVID-19 Severity Is Associated With Defective Immune Responses.
Kuijpers, Yunus; Chu, Xiaojing; Jaeger, Martin; Moorlag, Simone J C F M; Koeken, Valerie A C M; Zhang, Bowen; de Nooijer, Aline; Grondman, Inge; Gupta, Manoj Kumar; Janssen, Nico; Mourits, Vera P; de Bree, L Charlotte J; de Mast, Quirijn; van de Veerdonk, Frank L; Joosten, Leo A B; Li, Yang; Netea, Mihai G; Xu, Cheng-Jian.
  • Kuijpers Y; Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • Chu X; TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • Jaeger M; Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • Moorlag SJCFM; TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • Koeken VACM; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
  • Zhang B; Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • de Nooijer A; Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • Grondman I; Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • Gupta MK; TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • Janssen N; Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • Mourits VP; Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • de Bree LCJ; TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • de Mast Q; Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • van de Veerdonk FL; Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • Joosten LAB; Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • Li Y; TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  • Netea MG; Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
  • Xu CJ; Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
Front Immunol ; 13: 859387, 2022.
Article in English | MEDLINE | ID: covidwho-1924095
ABSTRACT
Recent genome-wide association studies (GWASs) of COVID-19 patients of European ancestry have identified genetic loci significantly associated with disease severity. Here, we employed the detailed clinical, immunological and multi-omics dataset of the Human Functional Genomics Project (HFGP) to explore the physiological significance of the host genetic variants that influence susceptibility to severe COVID-19. A genomics investigation intersected with functional characterization of individuals with high genetic risk for severe COVID-19 susceptibility identified several major patterns i. a large impact of genetically determined innate immune responses in COVID-19, with ii. increased susceptibility for severe disease in individuals with defective cytokine production; iii. genetic susceptibility related to ABO blood groups is probably mediated through the von Willebrand factor (VWF) and endothelial dysfunction. We further validated these identified associations at transcript and protein levels by using independent disease cohorts. These insights allow a physiological understanding of genetic susceptibility to severe COVID-19, and indicate pathways that could be targeted for prevention and therapy.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Genome-Wide Association Study / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.859387

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Genome-Wide Association Study / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.859387