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

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Item Type:Article
Title:Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01
Creators Name:Weiner, J. and Suwalski, P. and Holtgrewe, M. and Rakitko, A. and Thibeault, C. and Müller, M. and Patriki, D. and Quedenau, C. and Krüger, U. and Ilinsky, V. and Popov, I. and Balnis, J. and Jaitovich, A. and Helbig, E.T. and Lippert, L.J. and Stubbemann, P. and Real, L.M. and Macías, J. and Pineda, J.A. and Fernandez-Fuertes, M. and Wang, X. and Karadeniz, Z. and Saccomanno, J. and Doehn, J.M. and Hübner, R.H. and Hinzmann, B. and Salvo, M. and Blueher, A. and Siemann, S. and Jurisic, S. and Beer, J.H. and Rutishauser, J. and Wiggli, B. and Schmid, H. and Danninger, K. and Binder, R. and Corman, V.M. and Mühlemann, B. and Arjun Arkal, R. and Fragiadakis, G.K. and Mick, E. and Calfee, C.S. and Erle, D.J. and Hendrickson, C.M. and Kangelaris, K.N. and Krummel, M.F. and Woodruff, P.G. and Langelier, C.R. and Venkataramani, U. and García, F. and Zyla, J. and Drosten, C. and Braun, A. and Jones, T.C. and Suttorp, N. and Witzenrath, M. and Hippenstiel, S. and Zemojtel, T. and Skurk, C. and Wolfgang, P. and Borodina, T. and Ripke, S. and Sander, L.E. and Beule, D. and Landmesser, U. and Guettouche, T. and Kurth, F. and Heidecker, B.
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*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.
Keywords:SARS-CoV-2, COVID-19, Human Leukocyte Antigen, Intubation
Publisher:Elsevier / Lancet
Page Range:101099
Date:October 2021
Official Publication:https://doi.org/10.1016/j.eclinm.2021.101099
PubMed:View item in PubMed

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