%0 Journal Article
%A Weiner, January
%A Suwalski, Phillip
%A Holtgrewe, Manuel
%A Rakitko, Alexander
%A Thibeault, Charlotte
%A Müller, Melina
%A Patriki, Dimitri
%A Quedenau, Claudia
%A Krüger, Ulrike
%A Ilinsky, Valery
%A Popov, Iaroslav
%A Balnis, Joseph
%A Jaitovich, Ariel
%A Helbig, Elisa T
%A Lippert, Lena J
%A Stubbemann, Paula
%A Real, Luis M
%A Macías, Juan
%A Pineda, Juan A
%A Fernandez-Fuertes, Marta
%A Wang, Xiaomin
%A Karadeniz, Zehra
%A Saccomanno, Jacopo
%A Doehn, Jan-Moritz
%A Hübner, Ralf-Harto
%A Hinzmann, Bernd
%A Salvo, Mauricio
%A Blueher, Anja
%A Siemann, Sandra
%A Jurisic, Stjepan
%A Beer, Juerg H
%A Rutishauser, Jonas
%A Wiggli, Benedikt
%A Schmid, Hansruedi
%A Danninger, Kathrin
%A Binder, Ronald
%A Corman, Victor M
%A Mühlemann, Barbara
%A Arjun Arkal, Rao
%A Fragiadakis, Gabriela K
%A Mick, Eran
%A Comet, Consortium
%A Calfee, Carolyn S
%A Erle, David J
%A Hendrickson, Carolyn M
%A Kangelaris, Kirsten N
%A Krummel, Matthew F
%A Woodruff, Prescott G
%A Langelier, Charles R
%A Venkataramani, Urmila
%A García, Federico
%A Zyla, Joanna
%A Drosten, Christian
%A Alice, Braun
%A Jones, Terry C
%A Suttorp, Norbert
%A Witzenrath, Martin
%A Hippenstiel, Stefan
%A Zemojtel, Tomasz
%A Skurk, Carsten
%A Poller, Wolfgang
%A Borodina, Tatiana
%A Pa-Covid, Study Group
%A Ripke, Stephan
%A Sander, Leif E
%A Beule, Dieter
%A Landmesser, Ulf
%A Guettouche, Toumy
%A Kurth, Florian
%A Heidecker, Bettina
%T Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01.
%D 2021
%U https://hdl.handle.net/10668/27242
%X Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funded by Roche Sequencing Solutions, Inc.
%K COVID-19
%K Genetics
%K Human Leukocyte Antigen
%K SARS-CoV-2
%K intubation
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