1. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01
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Weiner 3rd, 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, Arjun Arkal, Rao, Fragiadakis, Gabriela K., Mick, Eran, Consortium COMET, 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, Study Group Pa-COVID, Ripke, Stephan, Sander, Leif E., Beule, Dieter, Landmesser, Ulf, Guettouche, Toumy, Kurth, Florian, Heidecker, Bettina, [Weiner, January] Charite Univ Med Berlin, Core Unit Bioinformat Berlin, Berlin Inst Hlth, DE-10178 Berlin, Germany, [Beule, Dieter] Charite Univ Med Berlin, Core Unit Bioinformat Berlin, Berlin Inst Hlth, DE-10178 Berlin, Germany, [Suwalski, Phillip] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Mueller, Melina] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Wang, Xiaomin] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Karadeniz, Zehra] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Skurk, Carsten] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Poller, Wolfgang] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Landmesser, Ulf] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Heidecker, Bettina] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Suwalski, Phillip] Charite, Berliner Simulat & Trainingszentrum, DE-10117 Berlin, Germany, [Holtgrewe, Manuel] Charite Univ Med Berlin, Berlin Inst Hlth, Core Unit Genom Berlin, DE-10178 Berlin, Germany, [Krueger, Ulrike] Charite Univ Med Berlin, Berlin Inst Hlth, Core Unit Genom Berlin, DE-10178 Berlin, Germany, [Zemojtel, Tomasz] Charite Univ Med Berlin, Berlin Inst Hlth, Core Unit Genom Berlin, DE-10178 Berlin, Germany, [Rakitko, Alexander] Genotek Ltd, Nastavnicheskii Pereulok 17-1, R-105120 Moscow, Russia, [Ilinsky, Valery] Genotek Ltd, Nastavnicheskii Pereulok 17-1, R-105120 Moscow, Russia, [Popov, Iaroslav] Genotek Ltd, Nastavnicheskii Pereulok 17-1, R-105120 Moscow, Russia, [Thibeault, Charlotte] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Helbig, Elisa T.] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Lippert, Lena J.] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Stubbemann, Paula] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Saccomanno, Jacopo] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Doehn, Jan-Moritz] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Huebner, Ralf-Harto] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Suttorp, Norbert] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Witzenrath, Martin] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Hippenstiel, Stefan] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Sander, Leif E.] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Kurth, Florian] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Patriki, Dimitri] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Jurisic, Stjepan] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Beer, Juerg H.] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Rutishauser, Jonas] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Wiggli, Benedikt] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Schmid, Hansruedi] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Quedenau, Claudia] Max Delbrueck Ctr Mol Med Berlin, DE-13125 Berlin, Germany, [Borodina, Tatiana] Max Delbrueck Ctr Mol Med Berlin, DE-13125 Berlin, Germany, [Balnis, Joseph] Albany Med Coll, Dept Mol & Cellular Physiol, Albany, NY 12208 USA, [Jaitovich, Ariel] Albany Med Coll, Dept Mol & Cellular Physiol, Albany, NY 12208 USA, [Real, Luis M.] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Macias, Juan] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Pineda, Juan A.] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Fernandez-Fuertes, Marta] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Hinzmann, Bernd] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Salvo, Mauricio] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Blueher, Anja] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Siemann, Sandra] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Guettouche, Toumy] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Danninger, Kathrin] Klinikum Wels Grieskirchen, Dept Cardiol & Intens Care, Wels, Austria, [Binder, Ronald] Klinikum Wels Grieskirchen, Dept Cardiol & Intens Care, Wels, Austria, [Corman, Victor M.] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Muehlemann, Barbara] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Drosten, Christian] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Jones, Terry C.] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Arkal, Rao Arjun] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Fragiadakis, Gabriela K.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Krummel, Matthew F.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Venkataramani, Urmila] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Arkal, Rao Arjun] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Fragiadakis, Gabriela K.] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Venkataramani, Urmila] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA, [Fragiadakis, Gabriela K.] Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA 94143 USA, [Mick, Eran] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Calfee, Carolyn S.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Hendrickson, Carolyn M.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Mick, Eran] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA, [Langelier, Charles R.] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA, [Mick, Eran] Chan Zuckerberg Biohub, San Francisco, CA USA, [Langelier, Charles R.] Chan Zuckerberg Biohub, San Francisco, CA USA, [Erle, David J.] COMET COVID 19 Multiphenotyping Effect Therapies, San Francisco, CA USA, [Consortium COMET] COMET COVID 19 Multiphenotyping Effect Therapies, San Francisco, CA USA, [Erle, David J.] Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA, [Kangelaris, Kirsten N.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA, [Arkal, Rao Arjun] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA, [Krummel, Matthew F.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, Sandler Asthma Basic Res Ctr, San Francisco, CA 94143 USA, [Garcia, Federico] Hosp Univ Clin San Cecilio, Inst Invest Ibs Granada, Granada, Spain, [Zyla, Joanna] Silesian Tech Univ, Dept Data Sci & Engn, Gliwice, Poland, [Alice, Braun] Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Charitepl 1, DE-10117 Berlin, Germany, [Ripke, Stephan] Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Charitepl 1, DE-10117 Berlin, Germany, [Jones, Terry C.] German Ctr Infect Res DZIF, Associated Partner Site, D-10117 Berlin, Germany, [Jones, Terry C.] Univ Cambridge, Ctr Pathogen Evolut, Dept Zool, Downing St, Cambridge CB2 3EJ, England, [Study Grp Pa-COVID] Pa COVID Study Grp, San Francisco, CA USA, [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet, Boston, MA 02114 USA, [Ripke, Stephan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA, [Landmesser, Ulf] Charite, Berlin Inst Hlth, Berlin, Germany, Roche Sequencing Solutions, Inc., Swiss National Science Foundation, Berlin Institutes of Health (B.I.H.), National Institutes of Health: NIH, Silesian University of Technology grant for Support and Development of Research Potential, NIAID-NIH CEIRS contract, NIH, German Research Foundation, German Ministry of Education and Research (BMBF), Berlin Institute of Health (CM-COVID), German Research Foundation (DFG), and Open Access Publication Fund of Charite - Universitatsmedizin Berlin
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SARS-CoV-2 ,Prevention ,Major histocompatibility complex ,Human Genome ,COVID-19 ,Pneumonia ,intubation ,Human Leukocyte Antigen ,Coronavirus ,Vaccine Related ,Emerging Infectious Diseases ,Infectious Diseases ,Good Health and Well Being ,Clinical Research ,FOS: Biological sciences ,Human Leukocyte Antigen  ,Genetics ,Pneumonia & Influenza ,2.1 Biological and endogenous factors ,Viral load ,Aetiology ,Lung ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit ,Research Paper - 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 COVID19 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. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
- Published
- 2021