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

  • Pablo Delgado-Wicke,
  • Sara Fernández de Córdoba-Oñate,
  • Emilia Roy-Vallejo,
  • Estíbaliz Alegría-Carrasco,
  • Diego A. Rodríguez-Serrano,
  • Amalia Lamana,
  • Nuria Montes,
  • Ana Nicolao-Gómez,
  • Rosa Carracedo-Rodríguez,
  • Ana Marcos-Jiménez,
  • Paula Díaz-Fernández,
  • José M. Galván-Román,
  • Laura Rabes-Rodríguez,
  • Marta Sanz-Alba,
  • Jesús Álvarez-Rodríguez,
  • Almudena Villa-Martí,
  • Carlos Rodríguez-Franco,
  • Gonzalo Villapalos-García,
  • Pablo Zubiaur,
  • Francisco Abad-Santos,
  • Ignacio de los Santos,
  • Rosa P. Gomariz,
  • Rosario García-Vicuña,
  • Cecilia Muñoz-Calleja,
  • Isidoro González-Álvaro,
  • Elena Fernández-Ruiz,
  • Carmen Suárez Fernández,
  • Ana Barrios,
  • Jesús Sanz,
  • Pedro Casado,
  • Ángela Gutiérrez,
  • Azucena Bautista,
  • Pilar Hernández,
  • Nuria Ruiz Giménez,
  • Berta Moyano,
  • Paloma Gil,
  • María Jesús Delgado,
  • Pedro Parra,
  • Beatriz Sánchez,
  • Carmen Sáez,
  • Marta Fernández-Rico,
  • Cristina Arévalo-Román,
  • Marianela Ciudad,
  • Santos Castañeda,
  • Irene Llorente,
  • Eva G. Tomero,
  • Noelia García-Castañeda,
  • Miren Uriarte,
  • Laura Cardeñoso,
  • Leticia Fontán García-Rodrigo,
  • Diego Domingo García,
  • Teresa Alarcón-Cavero,
  • María Auxiliadora Semiglia Chong,
  • Ainhoa Gutiérrez-Cobos,
  • Nelly D. Zurita-Cruz,
  • Francisco Sánchez-Madrid,
  • Enrique Martín-Gayo,
  • Ildefonso Sánchez-Cerrillo,
  • Pedro Martínez-Fleta,
  • Celia López-Sanz,
  • Ligia Gabrie,
  • Luciana del Campo-Guerola,
  • Reyes Tejedor,
  • Julio Ancochea,
  • Elena García-Castillo,
  • Elena Ávalos,
  • Ana Sánchez-Azofra,
  • Tamara Alonso,
  • Carolina Cisneros,
  • Claudia Valenzuela,
  • Francisco J. García-Pérez,
  • Rosa M. Girón,
  • Javier Aspa,
  • Celeste Marcos,
  • M. del Perpetuo Socorro Churruca,
  • Enrique Zamora,
  • Adrián Martínez,
  • Mar Barrio-Mayo,
  • Rosalina Henares-Espi,
  • Rosa Méndez,
  • David Arribas,
  • Marta Chicot-Llano,
  • Begoña González,
  • Begoña Quicios,
  • Pablo Patiño,
  • Marina Trigueros,
  • Cristina Dominguez-Peña,
  • David Jiménez-Jiménez,
  • Pablo Villamayor,
  • Alfonso Canabal,
  • Rafael de la Cámara,
  • Javier Ortiz,
  • Isabel Iturrate

摘要

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.