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 Aníbal Rodríguez-Serrano, Amalia Lamana, Núria Montés, Ana Nicolao-Gómez, Rosa Carracedo-Rodríguez, Ana Marcos‐Jiménez, Paula Díaz-Fernández, José María 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, PREDINMUN-COVID Group, 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
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.