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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Front+Immunol 2022 ; 13 (ä): 859387 Nephropedia Template TP
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The Genetic Risk for COVID-19 Severity Is Associated With Defective Immune Responses #MMPMID35634344
Kuijpers Y; Chu X; Jaeger M; Moorlag SJCFM; Koeken VACM; Zhang B; de Nooijer A; Grondman I; Gupta MK; Janssen N; Mourits VP; de Bree LCJ; de Mast Q; van de Veerdonk FL; Joosten LAB; Li Y; Netea MG; Xu CJ
Front Immunol 2022[]; 13 (ä): 859387 PMID35634344show ga
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.