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Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01
- Weiner, January;
- Suwalski, Phillip;
- Holtgrewe, Manuel;
- Rakitko, Alexander;
- Thibeault, Charlotte;
- Müller, Melina;
- Patriki, Dimitri;
- Quedenau, Claudia;
- Krüger, Ulrike;
- Ilinsky, Valery;
- Popov, Iaroslav;
- Balnis, Joseph;
- Jaitovich, Ariel;
- Helbig, Elisa T;
- Lippert, Lena J;
- Stubbemann, Paula;
- Real, Luis M;
- Macías, Juan;
- Pineda, Juan A;
- Fernandez-Fuertes, Marta;
- Wang, Xiaomin;
- Karadeniz, Zehra;
- Saccomanno, Jacopo;
- Doehn, Jan-Moritz;
- Hübner, Ralf-Harto;
- Hinzmann, Bernd;
- Salvo, Mauricio;
- Blueher, Anja;
- Siemann, Sandra;
- Jurisic, Stjepan;
- Beer, Juerg H;
- Rutishauser, Jonas;
- Wiggli, Benedikt;
- Schmid, Hansruedi;
- Danninger, Kathrin;
- Binder, Ronald;
- Corman, Victor M;
- Mühlemann, Barbara;
- Arkal, Rao Arjun;
- Fragiadakis, Gabriela K;
- Mick, Eran;
- COMET, Consortium;
- Calfee, Carolyn S;
- Erle, David J;
- Hendrickson, Carolyn M;
- Kangelaris, Kirsten N;
- Krummel, Matthew F;
- Woodruff, Prescott G;
- Langelier, Charles R;
- Venkataramani, Urmila;
- García, Federico;
- Zyla, Joanna;
- Drosten, Christian;
- Alice, Braun;
- Jones, Terry C;
- Suttorp, Norbert;
- Witzenrath, Martin;
- Hippenstiel, Stefan;
- Zemojtel, Tomasz;
- Skurk, Carsten;
- Poller, Wolfgang;
- Borodina, Tatiana;
- Pa-COVID, Study Group;
- Ripke, Stephan;
- Sander, Leif E;
- Beule, Dieter;
- Landmesser, Ulf;
- Guettouche, Toumy;
- Kurth, Florian;
- Heidecker, Bettina
Abstract
Background
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.Methods
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).Findings
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.Interpretation
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.Funding
Funded by Roche Sequencing Solutions, Inc.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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