Wicke, Pablo DelgadoFernández de Córdoba Oñate, SaraRoy Vallejo, EmiliaAlegría Carrasco, EstibalizRodríguez Serrano, Diego A.Lamana Domínguez, AmaliaMontes, NuriaNicolao Gómez, AnaCarracedo Rodríguez, RosaMarcos Jiménez, AnaDíaz Fernández, PaulaGalván Román, José M.Rabes Rodríguez, LauraSanz Alba, MartaÁlvarez Rodríguez, JesúsVilla Martí, AlmudenaRodríguez Franco, CarlosVillapalos García, GonzaloZubiaur, PabloAbad Santos, FranciscoDe los Santos, IgnacioPérez Gomáriz, Rosa MaríaGarcía Vicuña, RosarioMuñoz Calleja, CeciliaGonzález Álvaro, IsidoroFernández Ruiz, ElenaSuárez Fernández, CarmenBarrios, AnaSanz, JesúsCasado, PedroGutiérrez, ÁngelaBautista, AzucenaHernández, PilarRuiz Giménez, NuriaMoyano, BertaGil, PalomaDelgado, María JesúsParra, PedroSánchez, BeatrizSáez, CarmenFernández Rico, MartaArévalo Román, CristinaCiudad, MarianelaCastañeda, SantosLlorente, IreneTomero, Eva G.García Castañeda, NoeliaUriarte, MirenCardeñoso, LauraFontán García-Rodrigo, LeticiaDomingo García, DiegoAlarcón Cavero, TeresaSemiglia Chong, María AuxiliadoraGutiérrez Cobos, AinhoaZurita Cruz, Nelly D.Sánchez Madrid, FranciscoMartín Gayo, EnriqueSánchez Cerrillo, IldefonsoMartínez Fleta, PedroLópez Sanz, CeliaGabrie, LigiaDel Campo Guerola, LucianaTejedor, ReyesAncochea, JulioGarcía Castillo, ElenaÁvalos, ElenaSánchez Azofra, AnaAlonso, TamaraCisneros, CarolinaValenzuela, ClaudiaGarcía Pérez, Francisco J.Girón, Rosa M.Aspa, JavierMarcos, CelesteSocorro Churruca, M. del PerpetuoZamora, EnriqueMartínez, AdriánBarrio Mayo, MarHenares Espi, RosalinaMéndez, RosaArribas, DavidChicot Llano, MartaGonzález, BegoñaQuicios, BegoñaPatiño, PabloTrigueros, MarinaDominguez Peña, CristinaJiménez Jiménez, DavidVillamayor, PabloCanabal, AlfonsoDe la Cámara, RafaelOrtiz, JavierIturrate, Isabel2024-12-082024-12-082024-09Delgado-Wicke, P., Fernández de Córdoba-Oñate, S., Roy-Vallejo, E. et al. Genetic variants regulating the immune response improve the prediction of COVID-19 severity provided by clinical variables. Sci Rep 14, 20728 (2024). https://doi.org/10.1038/s41598-024-71476-210.1038/s41598-024-71476-2https://hdl.handle.net/20.500.14352/112192Funding: This study was funded with grants: “Fondos Supera COVID19” by Banco Santander and CRUE to CM-C and RPG; RD21/0002/0027, PI18/0371 and PI21/00526 to IG-Á; PI19/00096 and PI22/00428 to EF-R and RICORS RD21/0002/0004 to RPG from Ministerio de Ciencia e Innovación (Instituto de Salud Carlos III, ISCIII), co-funded by European Regional Development Fund (ERDF) “A way to make Europe”; and co-financed by the Community of Madrid (CAM) through the COVID 2019 Aid to IdeS. The work of ER-V and AM-J was funded by Rio-Hortega grants CM19/00149 and CM19/00254, respectively, from the Ministerio de Ciencia e Innovación (Instituto de Salud Carlos III, ISCIII) and co-funded by The ERDF "A way to make Europe"; GV-G and PD-F were co-financed by ISCIII and the European Social Fund (PFIS grants FI20/00090 and FI19/00092, respectively). PZ was financed by Universidad Autónoma de Madrid, Margarita Salas contract, grants for the requalification of the Spanish university system. EA-C and AN-G were financed by INVESTIGO (2022-C23.I01.P03.S0020-0000031) and INVESTIGO CAM (09-PIN1-00015.6/2022), by Ministerio de Ciencia e Innovación and CAM respectively, both financed by the European Union's Recovery, Transformation and Resilience Plan and NextGenerationEU.The characteristics of the host are crucial in the final outcome of COVID-19. Herein, the influence of genetic and clinical variants in COVID-19 severity was investigated in a total of 1350 patients. Twenty-one single nucleotide polymorphisms of genes involved in SARS-CoV-2 sensing as Toll-like-Receptor 7, antiviral immunity as the type I interferon signalling pathway (TYK2, STAT1, STAT4, OAS1, SOCS) and the vasoactive intestinal peptide and its receptors (VIP/VIPR1,2) were studied. To analyse the association between polymorphisms and severity, a model adjusted by age, sex and different comorbidities was generated by ordinal logistic regression. The genotypes rs8108236-AA (OR 0.12 [95% CI 0.02–0.53]; p = 0.007) and rs280519-AG (OR 0.74 [95% CI 0.56–0.99]; p = 0.03) in TYK2, and rs688136-CC (OR 0.7 [95% CI 0.5–0.99]; p = 0.046) in VIP, were associated with lower severity; in contrast, rs3853839-GG in TLR7 (OR 1.44 [95% CI 1.07–1.94]; p = 0.016), rs280500-AG (OR 1.33 [95% CI 0.97–1.82]; p = 0.078) in TYK2 and rs1131454-AA in OAS1 (OR 1.29 [95% CI 0.95–1.75]; p = 0.110) were associated with higher severity. Therefore, these variants could influence the risk of severe COVID-19.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal article2045-2322https://doi.org/10.1038/s41598-024-71476-2https://www.nature.com/articles/s41598-024-71476-2#citeasopen access575:61616.98:578.834Genética médicaEnfermedades infecciosasInmunologíaMicrobiología médica2410.07 Genética Humana3205.05 Enfermedades Infecciosas2412 Inmunología3201.03 Microbiología Clínica2407.02 Citogenética