1. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01
- Author
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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, and Heidecker, Bettina
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Coronaviruses ,Emerging Infectious Diseases ,Human Genome ,Clinical Research ,Infectious Diseases ,Genetics ,2.1 Biological and endogenous factors ,2.5 Research design and methodologies (aetiology) ,Good Health and Well Being ,SARS-CoV-2 ,COVID-19 ,Human Leukocyte Antigen  ,intubation ,Human Leukocyte Antigen ,Clinical sciences ,Health services and systems ,Public health - Abstract
BackgroundSince 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.MethodsWe 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).FindingsWe 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.InterpretationHLA-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.FundingFunded by Roche Sequencing Solutions, Inc.
- Published
- 2021