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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: |
Weiner, J.  ORCID: https://orcid.org/0000-0003-1438-7819, Suwalski, P., Holtgrewe, M. ORCID: https://orcid.org/0000-0002-3051-1763, Rakitko, A. ORCID: https://orcid.org/0000-0003-0567-7734, Thibeault, C., Müller, M., Patriki, D., Quedenau, C. ORCID: https://orcid.org/0000-0002-6846-4915, Krüger, U., Ilinsky, V. ORCID: https://orcid.org/0000-0003-4377-2759, 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. ORCID: https://orcid.org/0000-0002-7299-808X, 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. ORCID: https://orcid.org/0000-0002-2895-7969, Drosten, C., Braun, A. ORCID: https://orcid.org/0000-0003-1145-0261, Jones, T.C., Suttorp, N., Witzenrath, M., Hippenstiel, S., Zemojtel, T., Skurk, C., Wolfgang, P., Borodina, T. ORCID: https://orcid.org/0000-0002-6978-016X, Ripke, S., Sander, L.E., Beule, D. ORCID: https://orcid.org/0000-0002-3284-0632, Landmesser, U., Guettouche, T., Kurth, F. and Heidecker, B.
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| 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 |
| Source: | EClinicalMedicine |
| ISSN: | 2589-5370 |
| Publisher: | Elsevier / Lancet |
| Volume: | 40 |
| 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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