Camps-Vilaró, AnnaDegano, Irene R.Elosua Llanos, RobertoSubirana Cachinero, IsaacSolà-Richarte, ClàudiaNogués Solan, Francesc XavierMasclans Enviz, Joan RamonGüerri Fernández, RobertoMarin, JudithTizón-Marcos, HelenaVaquerizo Montilla, BeatrizMarrugat de la Iglesia, Jaume2024-10-252024-10-252024Camps-Vilaró A, Pinsach-Abuin ML, Degano IR, Ramos R, Martí-Lluch R, Elosua R, et al. Genetic characteristics involved in COVID-19 severity. The CARGENCORS case-control study and meta-analysis. J Med Virol. 2024 Feb;96(2):e29404. DOI: 10.1002/jmv.294040146-6615http://hdl.handle.net/10230/68347Pre-existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID-19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID-19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID-19 severity. CARGENCORS (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS-CoV-2 [COVID-19] virus) is an age- and sex-matched case-control study with 818 COVID-19 cases hospitalized with hypoxemia, and 1636 controls with COVID-19 treated at home. The association between severity and SNVs related to CAD (n = 32), inflammation (n = 19), thrombosis (n = 14), virus infectivity (n = 11), and two published to be related to COVID-19 severity was tested with adjusted logistic regression models. Two external independent cohorts were used for meta-analysis (SCOURGE and UK Biobank). After adjustment for potential confounders, 14 new SNVs were associated with COVID-19 severity in the CARGENCORS Study. These SNVs were related to CAD (n = 10), thrombosis (n = 2), and inflammation (n = 2). We also confirmed eight SNVs previously related to severe COVID-19 and virus infectivity. The meta-analysis showed five SNVs associated with severe COVID-19 in adjusted analyses (rs11385942, rs1561198, rs6632704, rs6629110, and rs12329760). We identified 14 novel SNVs and confirmed eight previously related to COVID-19 severity in the CARGENCORS data. In the meta-analysis, five SNVs were significantly associated to COVID-19 severity, one of them previously related to CAD.application/pdfeng© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/jmv.29404COVID-19SARS-CoV-2SNVsGeneticsSeveritySingle nucleotide variantsinfo:eu-repo/semantics/openAccess