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Weiner J, Suwalski P, Holtgrewe M, et al. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01. EClinicalMedicine. 2021;40:101099doi: 10.1016/j.eclinm.2021.101099.
Weiner, J., Suwalski, P., Holtgrewe, M., Rakitko, A., Thibeault, C., Müller, M., Patriki, D., Quedenau, C., Krüger, U., Ilinsky, V., Popov, I., Balnis, J., Jaitovich, A., Helbig, E. T., Lippert, L. J., Stubbemann, P., Real, L. M., Macías, J., Pineda, J. A., Fernandez-Fuertes, M., Wang, X., Karadeniz, Z., Saccomanno, J., Doehn, J. M., Hübner, R. H., Hinzmann, B., Salvo, M., Blueher, A., Siemann, S., Jurisic, S., Beer, J. H., Rutishauser, J., Wiggli, B., Schmid, H., Danninger, K., Binder, R., Corman, V. M., Mühlemann, B., Arjun Arkal, R., Fragiadakis, G. K., Mick, E., Comet, C., Calfee, C. S., Erle, D. J., Hendrickson, C. M., Kangelaris, K. N., Krummel, M. F., Woodruff, P. G., Langelier, C. R., Venkataramani, U., García, F., Zyla, J., Drosten, C., Alice, B., Jones, T. C., Suttorp, N., Witzenrath, M., Hippenstiel, S., Zemojtel, T., Skurk, C., Poller, W., Borodina, T., Pa-Covid, S. G., Ripke, S., Sander, L. E., Beule, D., Landmesser, U., Guettouche, T., Kurth, F., & Heidecker, B. (2021). Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01. EClinicalMedicine, 40101099. https://doi.org/10.1016/j.eclinm.2021.101099
Weiner, January, et al. "Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01." EClinicalMedicine vol. 40 (2021): 101099. doi: https://doi.org/10.1016/j.eclinm.2021.101099
Weiner J, Suwalski P, Holtgrewe M, Rakitko A, Thibeault C, Müller M, Patriki D, Quedenau C, Krüger U, Ilinsky V, Popov I, Balnis J, Jaitovich A, Helbig ET, Lippert LJ, Stubbemann P, Real LM, Macías J, Pineda JA, Fernandez-Fuertes M, Wang X, Karadeniz Z, Saccomanno J, Doehn JM, Hübner RH, Hinzmann B, Salvo M, Blueher A, Siemann S, Jurisic S, Beer JH, Rutishauser J, Wiggli B, Schmid H, Danninger K, Binder R, Corman VM, Mühlemann B, Arjun Arkal R, Fragiadakis GK, Mick E, Comet C, Calfee CS, Erle DJ, Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Langelier CR, Venkataramani U, García F, Zyla J, Drosten C, Alice B, Jones TC, Suttorp N, Witzenrath M, Hippenstiel S, Zemojtel T, Skurk C, Poller W, Borodina T, Pa-Covid SG, Ripke S, Sander LE, Beule D, Landmesser U, Guettouche T, Kurth F, Heidecker B. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01. EClinicalMedicine. 2021 Oct;40:101099. doi: 10.1016/j.eclinm.2021.101099. Epub 2021 Sep 02. PMID: 34490415; PMCID: PMC8410317.
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EClinicalMedicine. 2021 Oct;40:101099. doi: 10.1016/j.eclinm.2021.101099. Epub 2021 Sep 02.

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

EClinicalMedicine

January Weiner, Phillip Suwalski, Manuel Holtgrewe, Alexander Rakitko, Charlotte Thibeault, Melina Müller, Dimitri Patriki, Claudia Quedenau, Ulrike Krüger, Valery Ilinsky, Iaroslav Popov, Joseph Balnis, Ariel Jaitovich, Elisa T Helbig, Lena J Lippert, Paula Stubbemann, Luis M Real, Juan Macías, Juan A Pineda, Marta Fernandez-Fuertes, Xiaomin Wang, Zehra Karadeniz, Jacopo Saccomanno, Jan-Moritz Doehn, Ralf-Harto Hübner, Bernd Hinzmann, Mauricio Salvo, Anja Blueher, Sandra Siemann, Stjepan Jurisic, Juerg H Beer, Jonas Rutishauser, Benedikt Wiggli, Hansruedi Schmid, Kathrin Danninger, Ronald Binder, Victor M Corman, Barbara Mühlemann, Rao Arjun Arkal, Gabriela K Fragiadakis, Eran Mick, Consortium Comet, Carolyn S Calfee, David J Erle, Carolyn M Hendrickson, Kirsten N Kangelaris, Matthew F Krummel, Prescott G Woodruff, Charles R Langelier, Urmila Venkataramani, Federico García, Joanna Zyla, Christian Drosten, Braun Alice, Terry C Jones, Norbert Suttorp, Martin Witzenrath, Stefan Hippenstiel, Tomasz Zemojtel, Carsten Skurk, Wolfgang Poller, Tatiana Borodina, Study Group Pa-Covid, Stephan Ripke, Leif E Sander, Dieter Beule, Ulf Landmesser, Toumy Guettouche, Florian Kurth, Bettina Heidecker

Affiliations

  1. Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Bioinformatics Berlin, DE 10178, Germany.
  2. Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany.
  3. Berliner Simulations- und Trainingszentrum, Charite, Berlin, DE 10117, Germany.
  4. Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Genomics Berlin, DE 10178, Germany.
  5. Genotek Ltd., Nastavnicheskii pereulok 17/1, R 105120 Moscow, Russian Federation.
  6. Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany.
  7. Kantonsspital Baden AG, Department of Medicine, Baden, CH 5404, Switzerland.
  8. Max Delbrueck Center for Molecular Medicine Berlin, DE 13125, Germany.
  9. Department of Molecular and Cellular Physiology, Albany Medical College, NY, USA.
  10. Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, ES 41014, Spain.
  11. Roche Sequencing Solutions Pleasanton, USA 94588.
  12. Department of Cardiology and Intensive Care, Klinikum Wels-Grieskirchen, Wels, Austria.
  13. Charite Universitaetsmedizin Berlin, Institute of Virology Chariteplatz, 1 d-10117, Berlin, DE, 10117, Germany.
  14. ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  15. CoLabs, University of California San Francisco, San Francisco, CA, USA.
  16. Department of Pathology, University of California, San Francisco, CA, USA.
  17. Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  18. Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, CA, USA.
  19. Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  20. Chan Zuckerberg Biohub, San Francisco, CA, USA.
  21. COMET (COVID-19 Multiphenotyping for Effective Therapies) Consortium members are listed in the Supplementary Appendix 1.
  22. Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  23. Lung Biology Center, University of California, San Francisco, CA, USA.
  24. Department of Medicine, University of California, San Francisco, CA, USA.
  25. Sandler Asthma Basic Research Center, University of California, San Francisco, CA, USA.
  26. Hospital Universitario Clínico San Cecilio, Instituto de Investigación Ibs. Granada, Spain.
  27. Department of Data Science and Engineering, Silesian University of Technology, Gliwice, Poland.
  28. Charite Universitaetsmedizin Berlin, Dept. of Psychiatry and Psychotherapy Chariteplatz 1 d-10117 Berlin, DE 10117, Germany.
  29. German Center for Infection Research (DZIF), Associated Partner Site, 10117 Berlin, Germany.
  30. Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing St., Cambridge, CB2 3EJ, U.K.
  31. Pa-COVID Study Group, Members are listed in the Supplementary Appendix 2.
  32. Massachusetts General Hospital, Analytic and Translational Genetics, Boston, MA 02114, USA.
  33. Stanley Center for Psychiatry Research, Broad Institute of MIT and Harvard Cambridge MA 02142, USA.
  34. Berlin Institute of Health at Charité, Berlin, Germany.

PMID: 34490415 PMCID: PMC8410317 DOI: 10.1016/j.eclinm.2021.101099

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 (

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

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.

© 2021 The Authors.

Keywords: COVID-19; Genetics; Human Leukocyte Antigen; SARS-CoV-2; intubation

Conflict of interest statement

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 myocardi

Publication Types

Grant support