RT Journal Article
T1 Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01
A1 Weiner, January
A1 Suwalski, Phillip
A1 Holtgrewe, Manuel
A1 Rakitko, Alexander
A1 Thibeault, Charlotte
A1 Mueller, Melina
A1 Patriki, Dimitri
A1 Quedenau, Claudia
A1 Krueger, Ulrike
A1 Ilinsky, Valery
A1 Popov, Iaroslav
A1 Balnis, Joseph
A1 Jaitovich, Ariel
A1 Helbig, Elisa T.
A1 Lippert, Lena J.
A1 Stubbemann, Paula
A1 Real, Luis M.
A1 Macias, Juan
A1 Pineda, Juan A.
A1 Fernandez-Fuertes, Marta
A1 Wang, Xiaomin
A1 Karadeniz, Zehra
A1 Saccomanno, Jacopo
A1 Doehn, Jan-Moritz
A1 Huebner, Ralf-Harto
A1 Hinzmann, Bernd
A1 Salvo, Mauricio
A1 Blueher, Anja
A1 Siemann, Sandra
A1 Jurisic, Stjepan
A1 Beer, Juerg H.
A1 Rutishauser, Jonas
A1 Wiggli, Benedikt
A1 Schmid, Hansruedi
A1 Danninger, Kathrin
A1 Binder, Ronald
A1 Corman, Victor M.
A1 Muehlemann, Barbara
A1 Arkal, Rao Arjun
A1 Fragiadakis, Gabriela K.
A1 Mick, Eran
A1 Calfee, Carolyn S.
A1 Erle, David J.
A1 Hendrickson, Carolyn M.
A1 Kangelaris, Kirsten N.
A1 Krummel, Matthew F.
A1 Woodruff, Prescott G.
A1 Langelier, Charles R.
A1 Venkataramani, Urmila
A1 Garcia, Federico
A1 Zyla, Joanna
A1 Drosten, Christian
A1 Alice, Braun
A1 Jones, Terry C.
A1 Suttorp, Norbert
A1 Witzenrath, Martin
A1 Hippenstiel, Stefan
A1 Zemojtel, Tomasz
A1 Skurk, Carsten
A1 Poller, Wolfgang
A1 Borodina, Tatiana
A1 Ripke, Stephan
A1 Sander, Leif E.
A1 Beule, Dieter
A1 Landmesser, Ulf
A1 Guettouche, Toumy
A1 Kurth, Florian
A1 Heidecker, Bettina
A1 Consortium COMET, 
A1 Study Grp Pa-COVID, 
K1 SARS-CoV-2
K1 COVID-19
K1 Genetics
K1 Human Leukocyte Antigen&nbsp
K1 intubation
K1 Major histocompatibility complex
K1 Viral load
K1 Coronavirus
AB 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/)
PB Elsevier
YR 2021
FD 2021-10-25
LK http://hdl.handle.net/10668/18764
UL http://hdl.handle.net/10668/18764
LA en
DS RISalud
RD Apr 19, 2025