The Genetic Risk for COVID-19 Severity Is Associated With Defective Immune Responses.
COVID-19
cytokine
genome-wide association studies
genotyping
single-cell
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
21
01
2022
accepted:
19
04
2022
entrez:
31
5
2022
pubmed:
1
6
2022
medline:
3
6
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35634344
doi: 10.3389/fimmu.2022.859387
pmc: PMC9133558
doi:
Substances chimiques
von Willebrand Factor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
859387Informations de copyright
Copyright © 2022 Kuijpers, Chu, Jaeger, Moorlag, Koeken, Zhang, Nooijer, Grondman, Gupta, Janssen, Mourits, de Bree, de Mast, van de Veerdonk, Joosten, Li, Netea and Xu.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Viral Immunol. 2021 Jul-Aug;34(6):416-420
pubmed: 33902347
Nature. 2022 Mar;603(7902):587-598
pubmed: 35090163
PLoS Genet. 2014 May 15;10(5):e1004383
pubmed: 24830394
EClinicalMedicine. 2020 Jun 25;24:100434
pubmed: 32766543
Nat Commun. 2020 Nov 17;11(1):5859
pubmed: 33203833
N Engl J Med. 2021 Apr 22;384(16):1491-1502
pubmed: 33631065
J Clin Invest. 2020 May 1;130(5):2620-2629
pubmed: 32217835
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
Genome Biol. 2021 Aug 23;22(1):242
pubmed: 34425859
PLoS One. 2014 Apr 22;9(4):e95192
pubmed: 24755770
N Engl J Med. 2020 Oct 15;383(16):1522-1534
pubmed: 32558485
Cell. 2020 May 28;181(5):969-977
pubmed: 32437659
Lancet Haematol. 2020 Aug;7(8):e575-e582
pubmed: 32619411
Immunology. 2020 Mar;159(3):289-297
pubmed: 31671203
Nat Genet. 2022 Apr;54(4):382-392
pubmed: 35241825
Bioinformatics. 2012 May 15;28(10):1353-8
pubmed: 22492648
Cell. 2016 Nov 3;167(4):1125-1136.e8
pubmed: 27814509
Nat Med. 2021 Apr;27(4):659-667
pubmed: 33633408
Nat Rev Immunol. 2020 Sep;20(9):529-536
pubmed: 32728222
Thromb Haemost. 2018 Dec;118(12):2112-2125
pubmed: 30453346
Front Cardiovasc Med. 2020 Dec 04;7:584987
pubmed: 33344516
Lancet Infect Dis. 2020 Jun;20(6):669-677
pubmed: 32240634
J Invest Dermatol. 2005 Oct;125(4):615-28
pubmed: 16185259
Nat Med. 2021 Oct;27(10):1752-1760
pubmed: 34480127
Nature. 2020 Nov;587(7835):610-612
pubmed: 32998156
J Clin Invest. 2020 Oct 1;130(10):5591-5602
pubmed: 32692728
Genome Biol. 2021 Jul 6;22(1):198
pubmed: 34229738
Cell. 2016 Nov 3;167(4):1111-1124.e13
pubmed: 27814508
Nature. 2021 Mar;591(7848):92-98
pubmed: 33307546
Nature. 2015 Feb 19;518(7539):317-30
pubmed: 25693563
Science. 2020 Oct 23;370(6515):
pubmed: 32972996
J Med Virol. 2020 Nov;92(11):2768-2776
pubmed: 32543740
Thromb J. 2007 Sep 25;5:14
pubmed: 17894864
JAMA. 2020 Aug 18;324(7):663-673
pubmed: 32706371
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
Br J Haematol. 2020 Jul;190(1):27-28
pubmed: 32420611
Transfusion. 2020 Aug;60(8):1883-1884
pubmed: 32562280
Crit Care. 2020 Aug 12;24(1):496
pubmed: 32787887
Br J Anaesth. 2020 Sep;125(3):238-242
pubmed: 32731958
Nat Genet. 1995 Nov;11(3):241-7
pubmed: 7581446
Nature. 2021 Dec;600(7889):472-477
pubmed: 34237774
Hum Genet. 2021 Sep;140(9):1313-1328
pubmed: 34155559
Cell Rep. 2016 Nov 22;17(9):2474-2487
pubmed: 27818087
Clin Chim Acta. 2020 Oct;509:220-223
pubmed: 32562665
Signal Transduct Target Ther. 2021 Feb 22;6(1):85
pubmed: 33619245
EBioMedicine. 2021 Apr;66:103339
pubmed: 33867313
Cell. 2016 Nov 3;167(4):1099-1110.e14
pubmed: 27814507
Expert Rev Respir Med. 2020 Sep;14(9):865-868
pubmed: 32567404
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Nat Genet. 2018 Sep;50(9):1219-1224
pubmed: 30104762
Cell. 2020 Sep 17;182(6):1419-1440.e23
pubmed: 32810438
Nat Genet. 2016 Nov;48(11):1443-1448
pubmed: 27694958
J Thromb Haemost. 2017 Jul;15(7):1285-1294
pubmed: 28671350
Pathog Dis. 2016 Dec;74(9):
pubmed: 27915228
Lancet. 2020 Mar 28;395(10229):1033-1034
pubmed: 32192578
Blood Adv. 2020 Oct 27;4(20):4981-4989
pubmed: 33057633
Cell Host Microbe. 2020 Jun 10;27(6):992-1000.e3
pubmed: 32320677
J Intensive Care. 2020 May 24;8:36
pubmed: 32483488
Nat Rev Immunol. 2020 Jun;20(6):363-374
pubmed: 32346093
Nat Protoc. 2020 Sep;15(9):2759-2772
pubmed: 32709988
N Engl J Med. 2021 Jan 7;384(1):20-30
pubmed: 33332779
BMJ. 2020 May 22;369:m1985
pubmed: 32444460
Nature. 2020 Mar;579(7798):265-269
pubmed: 32015508
Nature. 2020 Jul;583(7816):437-440
pubmed: 32434211
J Infect Dis. 2021 Apr 23;223(8):1322-1333
pubmed: 33524124