Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01
Creators: name: Weiner 3rd, January
name: Suwalski, Phillip
name: Holtgrewe, Manuel
name: Rakitko, Alexander
name: Thibeault, Charlotte
name: Müller, Melina
name: Patriki, Dimitri
name: Quedenau, Claudia
name: Krüger, Ulrike
name: Ilinsky, Valery
name: Popov, Iaroslav
name: Balnis, Joseph
name: Jaitovich, Ariel
name: Helbig, Elisa T.
name: Lippert, Lena J.
name: Stubbemann, Paula
name: Real, Luis M.
name: Macías, Juan
name: Pineda, Juan A.
name: Fernandez-Fuertes, Marta
name: Wang, Xiaomin
name: Karadeniz, Zehra
name: Saccomanno, Jacopo
name: Doehn, Jan-Moritz
name: Hübner, Ralf-Harto
name: Hinzmann, Bernd
name: Salvo, Mauricio
name: Blueher, Anja
name: Siemann, Sandra
name: Jurisic, Stjepan
name: Beer, Juerg H.
name: Rutishauser, Jonas
name: Wiggli, Benedikt
name: Schmid, Hansruedi
name: Danninger, Kathrin
name: Binder, Ronald
name: Corman, Victor M.
name: Mühlemann, Barbara
name: Arjun Arkal, Rao
name: Fragiadakis, Gabriela K.
name: Mick, Eran
name: Consortium COMET
name: Calfee, Carolyn S.
name: Erle, David J.
name: Hendrickson, Carolyn M.
name: Kangelaris, Kirsten N.
name: Krummel, Matthew F.
name: Woodruff, Prescott G.
name: Langelier, Charles R.
name: Venkataramani, Urmila
name: García, Federico
name: Zyla, Joanna
name: Drosten, Christian
name: Alice, Braun
name: Jones, Terry C.
name: Suttorp, Norbert
name: Witzenrath, Martin
name: Hippenstiel, Stefan
name: Zemojtel, Tomasz
name: Skurk, Carsten
name: Poller, Wolfgang
name: Borodina, Tatiana
name: Study Group Pa-COVID
name: Ripke, Stephan
name: Sander, Leif E.
name: Beule, Dieter
name: Landmesser, Ulf
name: Guettouche, Toumy
name: Kurth, Florian
name: Heidecker, Bettina
Publisher: name: Charité - Universitätsmedizin Berlin
Year: 2021
Subjects: subject: SARS-CoV-2
subject: COVID-19
subject: Genetics
subject: FOS: Biological sciences
subject: Human Leukocyte Antigen
subject: intubation
subject: 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit

description: 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.