Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01.

Autor:	Weiner J; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Bioinformatics Berlin, DE 10178, Germany., Suwalski P; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany.; Berliner Simulations- und Trainingszentrum, Charite, Berlin, DE 10117, Germany., Holtgrewe M; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Genomics Berlin, DE 10178, Germany., Rakitko A; Genotek Ltd., Nastavnicheskii pereulok 17/1, R 105120 Moscow, Russian Federation., Thibeault C; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Müller M; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany., Patriki D; Kantonsspital Baden AG, Department of Medicine, Baden, CH 5404, Switzerland., Quedenau C; Max Delbrueck Center for Molecular Medicine Berlin, DE 13125, Germany., Krüger U; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Genomics Berlin, DE 10178, Germany., Ilinsky V; Genotek Ltd., Nastavnicheskii pereulok 17/1, R 105120 Moscow, Russian Federation., Popov I; Genotek Ltd., Nastavnicheskii pereulok 17/1, R 105120 Moscow, Russian Federation., Balnis J; Department of Molecular and Cellular Physiology, Albany Medical College, NY, USA., Jaitovich A; Department of Molecular and Cellular Physiology, Albany Medical College, NY, USA., Helbig ET; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Lippert LJ; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Stubbemann P; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Real LM; Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, ES 41014, Spain., Macías J; Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, ES 41014, Spain., Pineda JA; Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, ES 41014, Spain., Fernandez-Fuertes M; Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, ES 41014, Spain., Wang X; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany., Karadeniz Z; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany., Saccomanno J; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Doehn JM; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Hübner RH; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Hinzmann B; Roche Sequencing Solutions Pleasanton, USA 94588., Salvo M; Roche Sequencing Solutions Pleasanton, USA 94588., Blueher A; Roche Sequencing Solutions Pleasanton, USA 94588., Siemann S; Roche Sequencing Solutions Pleasanton, USA 94588., Jurisic S; Kantonsspital Baden AG, Department of Medicine, Baden, CH 5404, Switzerland., Beer JH; Kantonsspital Baden AG, Department of Medicine, Baden, CH 5404, Switzerland., Rutishauser J; Kantonsspital Baden AG, Department of Medicine, Baden, CH 5404, Switzerland., Wiggli B; Kantonsspital Baden AG, Department of Medicine, Baden, CH 5404, Switzerland., Schmid H; Kantonsspital Baden AG, Department of Medicine, Baden, CH 5404, Switzerland., Danninger K; Department of Cardiology and Intensive Care, Klinikum Wels-Grieskirchen, Wels, Austria., Binder R; Department of Cardiology and Intensive Care, Klinikum Wels-Grieskirchen, Wels, Austria., Corman VM; Charite Universitaetsmedizin Berlin, Institute of Virology Chariteplatz, 1 d-10117, Berlin, DE, 10117, Germany., Mühlemann B; Charite Universitaetsmedizin Berlin, Institute of Virology Chariteplatz, 1 d-10117, Berlin, DE, 10117, Germany., Arjun Arkal R; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.; CoLabs, University of California San Francisco, San Francisco, CA, USA.; Department of Pathology, University of California, San Francisco, CA, USA., Fragiadakis GK; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.; CoLabs, University of California San Francisco, San Francisco, CA, USA.; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Mick E; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, CA, USA.; Division of Infectious Diseases, University of California, San Francisco, CA, USA.; Chan Zuckerberg Biohub, San Francisco, CA, USA., Comet C; COMET (COVID-19 Multiphenotyping for Effective Therapies) Consortium members are listed in the Supplementary Appendix 1., Calfee CS; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, CA, USA., Erle DJ; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.; CoLabs, University of California San Francisco, San Francisco, CA, USA.; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, CA, USA.; COMET (COVID-19 Multiphenotyping for Effective Therapies) Consortium members are listed in the Supplementary Appendix 1.; Lung Biology Center, University of California, San Francisco, CA, USA.; Department of Medicine, University of California, San Francisco, CA, USA., Hendrickson CM; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, CA, USA., Kangelaris KN; Department of Medicine, University of California, San Francisco, CA, USA., Krummel MF; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.; Department of Pathology, University of California, San Francisco, CA, USA., Woodruff PG; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, CA, USA.; Department of Pathology, University of California, San Francisco, CA, USA.; Sandler Asthma Basic Research Center, University of California, San Francisco, CA, USA., Langelier CR; Division of Infectious Diseases, University of California, San Francisco, CA, USA.; Chan Zuckerberg Biohub, San Francisco, CA, USA., Venkataramani U; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.; CoLabs, University of California San Francisco, San Francisco, CA, USA., García F; Hospital Universitario Clínico San Cecilio, Instituto de Investigación Ibs. Granada, Spain., Zyla J; Department of Data Science and Engineering, Silesian University of Technology, Gliwice, Poland., Drosten C; Charite Universitaetsmedizin Berlin, Institute of Virology Chariteplatz, 1 d-10117, Berlin, DE, 10117, Germany., Alice B; Charite Universitaetsmedizin Berlin, Dept. of Psychiatry and Psychotherapy Chariteplatz 1 d-10117 Berlin, DE 10117, Germany., Jones TC; Charite Universitaetsmedizin Berlin, Institute of Virology Chariteplatz, 1 d-10117, Berlin, DE, 10117, Germany.; German Center for Infection Research (DZIF), Associated Partner Site, 10117 Berlin, Germany.; Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing St., Cambridge, CB2 3EJ, U.K., Suttorp N; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Witzenrath M; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Hippenstiel S; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Zemojtel T; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Genomics Berlin, DE 10178, Germany., Skurk C; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany., Poller W; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany., Borodina T; Max Delbrueck Center for Molecular Medicine Berlin, DE 13125, Germany., Pa-Covid SG; Pa-COVID Study Group, Members are listed in the Supplementary Appendix 2., Ripke S; Charite Universitaetsmedizin Berlin, Dept. of Psychiatry and Psychotherapy Chariteplatz 1 d-10117 Berlin, DE 10117, Germany.; Massachusetts General Hospital, Analytic and Translational Genetics, Boston, MA 02114, USA.; Stanley Center for Psychiatry Research, Broad Institute of MIT and Harvard Cambridge MA 02142, USA., Sander LE; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Beule D; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Bioinformatics Berlin, DE 10178, Germany., Landmesser U; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany.; Berlin Institute of Health at Charité, Berlin, Germany., Guettouche T; Roche Sequencing Solutions Pleasanton, USA 94588., Kurth F; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany., Heidecker B; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany.
Jazyk:	angličtina
Zdroj:	EClinicalMedicine [EClinicalMedicine] 2021 Oct; Vol. 40, pp. 101099. Date of Electronic Publication: 2021 Sep 02.
DOI:	10.1016/j.eclinm.2021.101099
Abstrakt:	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. Competing Interests: Bettina Heidecker, MD reports support from Roche Sequencing Solutions, Inc; a project grant from the Swiss National Science Foundation; is an inventor on patents that use RNA for diagnosis of myocarditis. Juerg H. Beer, MD reports grants from the Swiss National Foundation of Science, the Swiss Heart Foundation, the Foundation Kardio, Baden; Grant support to the institution from Bayer not related to this study; and lecture fee from Daiichi Sankyo to the institution. Martin Witzenrath, MD reports grants from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Deutsche Gesellschaft für Pneumologie, European Respiratory Society, Marie Curie Foundation, Else Kröner Fresenius Stiftung, Capnetz Stiftung, International Max Planck Research School, Quark Pharma, Takeda Pharma, Noxxon, Pantherna, Silence Therapeutics, Vaxxilon, Actelion, Bayer Health Care, Biotest, and Boehringer Ingelheim; consulting fees from Noxxon, Pantherna, Silence Therapeutics, Vaxxilon, Aptarion, Glaxo Smith Kline, Sinoxa, and Biotest; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra Zeneca, Berlin Chemie, Chiesi, Novartis, Teva, Actelion, Boehringer Ingelheim, Glaxo Smith Kline, Biotest, and Bayer Health Care; patent EPO 12,181,535.1: IL-27 for modulation of immune response in acute lung injury issued 2012, patent WO/2010/094,491: Means for inhibiting the expression of Ang-2 issued 2010, and patent DE 102,020,116,249.9: Camostat/ Niclosamide cotreatment in SARS-CoV-2 infected human lung cells issued 2020/21. Alexander Rakitko, Valery Ilinsky, and Iaroslav Popov are employees of Genotek Ltd. Melina Müller declares support for the present manuscript from Roche Sequencing Solutions and Swiss National Science Foundation and Berlin Institutes of Health. Joseph Balnis and Ariel Jaitovich declare support from the National Institute of Health (NIH, K01-HL130704). Bernd Hinzmann, Mauricio A Salvo, Anja Blüher, and Sandra Siemann declare support from Roche Sequencing Solutions. Carolyn Calfee reports NIH payment to her institution; payment from Roche/Genentech Payment and Bayer to her institution for observational study in ARDS; payment from Quantum Leap Healthcare Collaborative to her institution for adaptive platform Phase 2 trial in COVID-19; and consulting fees for novel therapies for ARDS from Vasomune and Quark Pharmaceuticals Payment. David J Erle reports NIH Grants to UCSF. Prescott G Woodruff reports support from Roche Sequencing Solutions, Inc., Swiss National Science Foundation, and Berlin Institutes of Health; US National Institutes of Health grant to his institution (U19AI077439) Charles Langelier reports NIH payment to his institution. Federico García reports grants from ViiV, MSD, and Roche; payment from Abbvie, Gilead, ViiV, MSD, and Roche; support for attending meetings and/or travel from Abbvie and Gilead; participation on a Data Safety Monitoring Board or Advisory Board for Gilead, ViiV, and Thera. Joanna Zyla has been supported by the Silesian University of Technology grant for Support and Development of Research Potential. Terry C. Jones reports a grant from Wellcome Trust, UK, on unrelated research on ancient viral DNA and an NIAID-NIH CEIRS grant (HHSN272201400008C). Leif Erik Sander reports Berlin Institutes of Health support to the PA-COVID-19 study group. Wolfgang Poller reports that this study was partially funded by Roche Sequencing Solutions, Inc., which also provided material for exome sequencing. Ulf Landmesser reports consulting fees from Abbott, Amgen, Bayer, Cardiac Dimensions, Novartis, Pfizer, and Omeicos; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Abott, NovoNordisk, Bayer, Amgen, DaiichiSankyo, Pfizer, Sanofi, Boson Scientific, Astra Zeneca, and Boehringer Ingelheim. All other authors have nothing to declare. (© 2021 The Authors.)
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