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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; Arjun Arkal, Rao; 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.
  • 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.
  • Holtgrewe M; Berliner Simulations- und Trainingszentrum, Charite, Berlin, DE 10117, Germany.
  • Rakitko A; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Genomics Berlin, DE 10178, Germany.
  • Thibeault C; Genotek Ltd., Nastavnicheskii pereulok 17/1, R 105120 Moscow, Russian Federation.
  • Müller M; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany.
  • Patriki D; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany.
  • Quedenau C; Kantonsspital Baden AG, Department of Medicine, Baden, CH 5404, Switzerland.
  • Krüger U; Max Delbrueck Center for Molecular Medicine Berlin, DE 13125, Germany.
  • Ilinsky V; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Genomics Berlin, DE 10178, Germany.
  • Popov I; Genotek Ltd., Nastavnicheskii pereulok 17/1, R 105120 Moscow, Russian Federation.
  • Balnis J; Genotek Ltd., Nastavnicheskii pereulok 17/1, R 105120 Moscow, Russian Federation.
  • Jaitovich A; Department of Molecular and Cellular Physiology, Albany Medical College, NY, USA.
  • Helbig ET; Department of Molecular and Cellular Physiology, Albany Medical College, NY, USA.
  • 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; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany.
  • 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; Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, ES 41014, Spain.
  • Karadeniz Z; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, Germany.
  • Saccomanno J; Department of Cardiology, Charite Universitaetsmedizin Berlin, DE 12203, 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; Charite Universitaetsmedizin Berlin, Department of Infectious Diseases and Respiratory Medicine Berlin, DE 10117, Germany.
  • 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; Roche Sequencing Solutions Pleasanton, USA 94588.
  • 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; Kantonsspital Baden AG, Department of Medicine, Baden, CH 5404, Switzerland.
  • Binder R; Department of Cardiology and Intensive Care, Klinikum Wels-Grieskirchen, Wels, Austria.
  • Corman VM; Department of Cardiology and Intensive Care, Klinikum Wels-Grieskirchen, Wels, Austria.
  • Mühlemann B; Charite Universitaetsmedizin Berlin, Institute of Virology Chariteplatz, 1 d-10117, Berlin, DE, 10117, Germany.
  • Arjun Arkal R; Charite Universitaetsmedizin Berlin, Institute of Virology Chariteplatz, 1 d-10117, Berlin, DE, 10117, Germany.
  • Fragiadakis GK; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Mick E; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Comet C; Department of Pathology, University of California, San Francisco, CA, USA.
  • Calfee CS; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Erle DJ; CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Hendrickson CM; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Kangelaris KN; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Krummel MF; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Woodruff PG; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Langelier CR; COMET (COVID-19 Multiphenotyping for Effective Therapies) Consortium members are listed in the Supplementary Appendix 1.
  • Venkataramani U; Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, CA, USA.
EClinicalMedicine ; 40: 101099, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1385454
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*0401 with severe clinical course of COVID-19. Carriers of HLA-C*0401 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*0401 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles.

INTERPRETATION:

HLA-C*0401 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.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Etiology study / Prognostic study / Reviews / Risk factors Language: English Journal: EClinicalMedicine Year: 2021 Document Type: Article Affiliation country: J.eclinm.2021.101099

Full text: Available Collection: International databases Database: MEDLINE Type of study: Etiology study / Prognostic study / Reviews / Risk factors Language: English Journal: EClinicalMedicine Year: 2021 Document Type: Article Affiliation country: J.eclinm.2021.101099