Frontiers in Immunology (May 2022)
The Genetic Risk for COVID-19 Severity Is Associated With Defective Immune Responses
- Yunus Kuijpers,
- Yunus Kuijpers,
- Xiaojing Chu,
- Xiaojing Chu,
- Xiaojing Chu,
- Martin Jaeger,
- Simone J. C. F. M. Moorlag,
- Valerie A. C. M. Koeken,
- Valerie A. C. M. Koeken,
- Valerie A. C. M. Koeken,
- Bowen Zhang,
- Bowen Zhang,
- Aline de Nooijer,
- Inge Grondman,
- Manoj Kumar Gupta,
- Manoj Kumar Gupta,
- Nico Janssen,
- Vera P. Mourits,
- L. Charlotte J. de Bree,
- Quirijn de Mast,
- Frank L. van de Veerdonk,
- Leo A. B. Joosten,
- Leo A. B. Joosten,
- Yang Li,
- Yang Li,
- Yang Li,
- Mihai G. Netea,
- Mihai G. Netea,
- Cheng-Jian Xu,
- Cheng-Jian Xu,
- Cheng-Jian Xu,
- Cheng-Jian Xu
Affiliations
- Yunus Kuijpers
- Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- Yunus Kuijpers
- 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
- Xiaojing Chu
- Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- Xiaojing Chu
- 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
- Xiaojing Chu
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Martin Jaeger
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Simone J. C. F. M. Moorlag
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Valerie A. C. M. Koeken
- Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- Valerie A. C. M. Koeken
- 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
- Valerie A. C. M. Koeken
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Bowen Zhang
- Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- Bowen Zhang
- 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
- Aline de Nooijer
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Inge Grondman
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Manoj Kumar Gupta
- Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- Manoj Kumar Gupta
- 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
- Nico Janssen
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Vera P. Mourits
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- L. Charlotte J. de Bree
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Quirijn de Mast
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Frank L. van de Veerdonk
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Leo A. B. Joosten
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Leo A. B. Joosten
- Núcleo de Pesquisa da Faculdade da Polícia Militar (FPM) do Estado de Goiás, Goiânia, Brazil
- Yang Li
- Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- Yang Li
- 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
- Yang Li
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Mihai G. Netea
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Mihai G. Netea
- Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany
- Cheng-Jian Xu
- Centre for Individualised Infection Medicine, CiiM, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
- Cheng-Jian Xu
- 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
- Cheng-Jian Xu
- Department of Internal Medicine and Radboud Institute for Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Cheng-Jian Xu
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- DOI
- https://doi.org/10.3389/fimmu.2022.859387
- Journal volume & issue
-
Vol. 13
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.
Keywords
