dc.creator | Weiner, January | es |
dc.creator | Suwalski, Phillip | es |
dc.creator | Holtgrewe, Manuel | es |
dc.creator | Rakitko, Alexander | es |
dc.creator | Macías Sánchez, Juan | es |
dc.creator | Pineda Vergara, Juan Antonio | es |
dc.creator | Heidecker, Bettina | es |
dc.date.accessioned | 2022-10-11T14:31:49Z | |
dc.date.available | 2022-10-11T14:31:49Z | |
dc.date.issued | 2021-09-02 | |
dc.identifier.citation | Weiner, J., Suwalski, P., Holtgrewe, M., Rakitko, A., Macías Sánchez, J., Pineda Vergara, J.A. y Heidecker, B. (2021). Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01. EClinicalMedicine, 40, 101099. https://doi.org/10.1016/j.eclinm.2021.101099. | |
dc.identifier.issn | 2589-5370 | es |
dc.identifier.uri | https://hdl.handle.net/11441/137815 | |
dc.description.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. | es |
dc.format | application/pdf | es |
dc.format.extent | 12 p. | es |
dc.language.iso | eng | es |
dc.relation.ispartof | EClinicalMedicine, 40, 101099. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | SARS-CoV-2 | es |
dc.subject | COVID-19 | es |
dc.subject | Genetics | es |
dc.subject | Human Leukocyte Antigen | es |
dc.subject | Intubation | es |
dc.title | Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01 | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S2589537021003795?via%3Dihub | es |
dc.identifier.doi | 10.1016/j.eclinm.2021.101099 | es |
dc.journaltitle | EClinicalMedicine | es |
dc.publication.volumen | 40 | es |
dc.publication.initialPage | 101099 | |