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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Pairo-Castineira, Erola | es-ES |
dc.contributor.author | Clohisey, Sara | es-ES |
dc.contributor.author | Klaric, Lucija | es-ES |
dc.contributor.author | SERRANO RUIZ, ALFREDO | es-ES |
dc.date.accessioned | 2023-09-13T09:58:49Z | - |
dc.date.available | 2023-09-13T09:58:49Z | - |
dc.date.issued | 2021-03-04 | es_ES |
dc.identifier.issn | 1476-4687 | es_ES |
dc.identifier.uri | https://doi.org/10.1038/s41586-020-03065-y | es_ES |
dc.description | Artículos en revistas | es_ES |
dc.description.abstract | . | es-ES |
dc.description.abstract | Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10−8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice. | en-GB |
dc.format.mimetype | application/pdf | es_ES |
dc.language.iso | en-GB | es_ES |
dc.rights | es_ES | |
dc.rights.uri | es_ES | |
dc.source | Revista: Nature, Periodo: 1, Volumen: 591, Número: 7848, Página inicial: 92, Página final: 98 | es_ES |
dc.title | Genetic mechanisms of critical illness in COVID-19 | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.description.version | info:eu-repo/semantics/publishedVersion | es_ES |
dc.rights.holder | la editorial no permite el depóstio en abierto | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/restrictedAccess | es_ES |
dc.keywords | . | es-ES |
dc.keywords | Genetic variants Critical illness Therapeutic development Repurposing of medications Clinical trials | en-GB |
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