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. 2024 Sep 5;14(1):20728.
doi: 10.1038/s41598-024-71476-2.

Genetic variants regulating the immune response improve the prediction of COVID-19 severity provided by clinical variables

Pablo Delgado-Wicke #  1 , Sara Fernández de Córdoba-Oñate #  2   3   4 , Emilia Roy-Vallejo  5 , Estíbaliz Alegría-Carrasco  1 , Diego A Rodríguez-Serrano  6 , Amalia Lamana  7 , Nuria Montes  2   8   9 , Ana Nicolao-Gómez  1 , Rosa Carracedo-Rodríguez  1 , Ana Marcos-Jiménez  10 , Paula Díaz-Fernández  10 , José M Galván-Román  5 , Laura Rabes-Rodríguez  5 , Marta Sanz-Alba  5 , Jesús Álvarez-Rodríguez  5 , Almudena Villa-Martí  5 , Carlos Rodríguez-Franco  5 , Gonzalo Villapalos-García  11   12 , Pablo Zubiaur  11   12 , Francisco Abad-Santos  11   12 , Ignacio de Los Santos  5   13 , Rosa P Gomariz  7 , Rosario García-Vicuña  2   14 , Cecilia Muñoz-Calleja  10   14   13 , Isidoro González-Álvaro #  15 , Elena Fernández-Ruiz #  16   17 ; PREDINMUN-COVID Group
Collaborators, Affiliations

Genetic variants regulating the immune response improve the prediction of COVID-19 severity provided by clinical variables

Pablo Delgado-Wicke et al. Sci Rep. .

Abstract

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.

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Conflict of interest statement

TFA-S has been consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Aptatargets, Chemo, FAES, Farmalider, Ferrer, Galenicum, GlaxoSmithKline, Gilead, Italfarmaco, Janssen-427 Cilag, Kern, Normon, Novartis, Servier, Teva and Zambon. IG-Á reports personal fees from Lilly and Sanofi; personal fees and non-financial support from BMS; personal fees and non-financial support from Abbvie; research support, personal fees and non-financial support from Roche Laboratories; research support from Gebro Pharma; non-financial support from MSD, Pfizer and Novartis, not related to the submitted work. RGV declares educational or research grants for her institution from Abbvie, Lilly, Janssen, MSD, Novartis, Sanofi and UCB; consultancies/speaking personal fees from Abbvie, Biogen, MSD, Pfizer, Sandoz and UCB; non-financial support from Abbvie, Janssen, Lilly, MSD, Novartis, Pfizer and UCB, all outside the present work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Predicted probability of COVID-19 severity for each significant SNP in the clinical model. Numbers inside each graph bar indicate the predicted probability of COVID-19 severity as percentage (95% confidence interval) for each genotype: OAS1 rs1131454, TLR7 rs3853839, TYK2 rs280500, rs280519 and rs8108236, and VIP rs688136. Upper horizontal lines indicate significant p-values and Odds ratios from the multivariable analysis in which each SNP was included separately in the clinical model.
Fig. 2
Fig. 2
Forest plot of the final multivariable model with clinical and genetic variables. The Odds ratios (dots) and 95% confidence intervals (horizontal bars) for all variables are depicted. ORs = 1 correspond to reference conditions and are represented by grey dots, as well as non-significant conditions. Conditions that significantly increase the probability of developing severe COVID-19 are represented by red dots, while those conditions significantly associated with the development of mild COVID-19 are represented in blue (p < 0.05). HIV human immunodeficiency virus, DM Diabetes mellitus, AHT arterial hypertension.
See this image and copyright information in PMC

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