Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID-19

Rosario López-Rodríguez; Marta Del Pozo-Valero; Marta Corton; Pablo Minguez; Javier Ruiz-Hornillos; María Elena Pérez-Tomás; María Barreda-Sánchez; Esther Mancebo; Cristina Villaverde; Gonzalo Núñez-Moreno; Raquel Romero; Estela Paz-Artal; Encarna Guillén-Navarro; Berta Almoguera; Carmen Ayuso; Lidia Fernández-Caballero; Ruth Fernández Sanchez; Inés García Vara; Laura Marzal Gordo; Andrea Martinez-Ramas; Lorena Ondo; Miguel Górgolas; Alfonso Cabello; Germán Peces Barba; Sara Heili; César Calvo; María Dolores Martín Ríos; Arnoldo Santos; Olga Sánchez-Pernaute; Lucía Llanos; Sandra Zazo; Federico Rojo; Felipe Villar; Raimundo de Andrés; Ignacio Jiménez Alfaro; Ignacio Gadea; Celia Perales; Yolanda Cañadas Juarez; Ignacio Mahillo; Antonio Herrero; Juan Carlos Taracido; Elisa García-Vázquez; Rubén Jara-Rubio; José A. Pons-Miñano; Juana M. Marín-Martínez; M. Teresa Herranz-Marín; Enrique Bernal-Morell; Josefina García-García; Juan de Dios González-Caballero; M. Dolores Chirlaque-López; Alfredo Minguela-Puras; Manuel Muro-Amador; Antonio Moreno-Docón; Genoveva Yagüe-Guirao; José M. Abellán-Perpiñán; Jorge E. Martínez-Pérez; Fernando I. Sánchez-Martínez; Alberto Utrero-Rico; Mario Fernández-Ruiz; Octavio Carretero; José María Aguado; Rocio Laguna-Goya; Ángel Jiménez; María Herrera Abián; Mercedes García Salmones; Lidia Gagliardi Alarcon; María Rubio Oliveira; Carlos Fabian Castaño Romero; Carlos Aranda Cosgaya; Virginia Víctor Palomares; Leticia García Rodríguez; Maria Sanchez Carpintero Abad; Mª Carmen García Torrejón

doi:10.1038/s41598-022-14035-x

Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID-19

Rosario López-Rodríguez, Marta Del Pozo-Valero, Marta Corton, Pablo Minguez, Javier Ruiz-Hornillos, María Elena Pérez-Tomás, María Barreda-Sánchez, Esther Mancebo, Cristina Villaverde, Gonzalo Núñez-Moreno, Raquel Romero, Estela Paz-Artal, Encarna Guillén-Navarro, Berta Almoguera, Carmen Ayuso, Lidia Fernández-Caballero, Ruth Fernández Sanchez, Inés García Vara, Laura Marzal Gordo, Andrea Martinez-RamasLorena Ondo, Miguel Górgolas, Alfonso Cabello, Germán Peces Barba, Sara Heili, César Calvo, María Dolores Martín Ríos, Arnoldo Santos, Olga Sánchez-Pernaute, Lucía Llanos, Sandra Zazo, Federico Rojo, Felipe Villar, Raimundo de Andrés, Ignacio Jiménez Alfaro, Ignacio Gadea, Celia Perales, Yolanda Cañadas Juarez, Ignacio Mahillo, Antonio Herrero, Juan Carlos Taracido, Elisa García-Vázquez, Rubén Jara-Rubio, José A. Pons-Miñano, Juana M. Marín-Martínez, M. Teresa Herranz-Marín, Enrique Bernal-Morell, Josefina García-García, Juan de Dios González-Caballero, M. Dolores Chirlaque-López, Alfredo Minguela-Puras, Manuel Muro-Amador, Antonio Moreno-Docón, Genoveva Yagüe-Guirao, José M. Abellán-Perpiñán, Jorge E. Martínez-Pérez, Fernando I. Sánchez-Martínez, Alberto Utrero-Rico, Mario Fernández-Ruiz, Octavio Carretero, José María Aguado, Rocio Laguna-Goya, Ángel Jiménez, María Herrera Abián, Mercedes García Salmones, Lidia Gagliardi Alarcon, María Rubio Oliveira, Carlos Fabian Castaño Romero, Carlos Aranda Cosgaya, Virginia Víctor Palomares, Leticia García Rodríguez, Maria Sanchez Carpintero Abad, Mª Carmen García Torrejón

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Abstract

Rare variants affecting host defense against pathogens could be involved in COVID-19 severity and may help explain fatal outcomes in young and middle-aged patients. Our aim was to report the presence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected group of COVID-19 patients under 65 years who required intubation or resulting in death (n = 44). To this end, different etiopathogenic mechanisms were explored using gene prioritization-based analysis in which genes involved in immune response, immunodeficiencies or blood coagulation were studied. We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic and were located in genes mainly involved in immune response. A network analysis, including the 42 genes with candidate variants, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks composed by genes enriched in carbohydrate metabolism and in DNA metabolism and repair processes. In conclusion, we have detected candidate variants that may potentially influence COVID-19 outcome in our cohort of patients. Further studies are needed to confirm the ultimate role of the genetic variants described in the present study on COVID-19 severity.

Original language	English
Article number	10369
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-14035-x
State	Published - Dec 2022
Externally published	Yes

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López-Rodríguez, R., Del Pozo-Valero, M., Corton, M., Minguez, P., Ruiz-Hornillos, J., Pérez-Tomás, M. E., Barreda-Sánchez, M., Mancebo, E., Villaverde, C., Núñez-Moreno, G., Romero, R., Paz-Artal, E., Guillén-Navarro, E., Almoguera, B., Ayuso, C., Fernández-Caballero, L., Fernández Sanchez, R., García Vara, I., Marzal Gordo, L., ... Torrejón, M. C. G. (2022). Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID-19. Scientific Reports, 12(1), Article 10369. https://doi.org/10.1038/s41598-022-14035-x

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title = "Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID-19",

abstract = "Rare variants affecting host defense against pathogens could be involved in COVID-19 severity and may help explain fatal outcomes in young and middle-aged patients. Our aim was to report the presence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected group of COVID-19 patients under 65 years who required intubation or resulting in death (n = 44). To this end, different etiopathogenic mechanisms were explored using gene prioritization-based analysis in which genes involved in immune response, immunodeficiencies or blood coagulation were studied. We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic and were located in genes mainly involved in immune response. A network analysis, including the 42 genes with candidate variants, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks composed by genes enriched in carbohydrate metabolism and in DNA metabolism and repair processes. In conclusion, we have detected candidate variants that may potentially influence COVID-19 outcome in our cohort of patients. Further studies are needed to confirm the ultimate role of the genetic variants described in the present study on COVID-19 severity.",

author = "Rosario L{\'o}pez-Rodr{\'i}guez and {Del Pozo-Valero}, Marta and Marta Corton and Pablo Minguez and Javier Ruiz-Hornillos and P{\'e}rez-Tom{\'a}s, {Mar{\'i}a Elena} and Mar{\'i}a Barreda-S{\'a}nchez and Esther Mancebo and Cristina Villaverde and Gonzalo N{\'u}{\~n}ez-Moreno and Raquel Romero and Estela Paz-Artal and Encarna Guill{\'e}n-Navarro and Berta Almoguera and Carmen Ayuso and Lidia Fern{\'a}ndez-Caballero and {Fern{\'a}ndez Sanchez}, Ruth and {Garc{\'i}a Vara}, In{\'e}s and {Marzal Gordo}, Laura and Andrea Martinez-Ramas and Lorena Ondo and Miguel G{\'o}rgolas and Alfonso Cabello and Barba, {Germ{\'a}n Peces} and Sara Heili and C{\'e}sar Calvo and R{\'i}os, {Mar{\'i}a Dolores Mart{\'i}n} and Arnoldo Santos and Olga S{\'a}nchez-Pernaute and Luc{\'i}a Llanos and Sandra Zazo and Federico Rojo and Felipe Villar and {de Andr{\'e}s}, Raimundo and Alfaro, {Ignacio Jim{\'e}nez} and Ignacio Gadea and Celia Perales and Juarez, {Yolanda Ca{\~n}adas} and Ignacio Mahillo and Antonio Herrero and Taracido, {Juan Carlos} and Elisa Garc{\'i}a-V{\'a}zquez and Rub{\'e}n Jara-Rubio and Pons-Mi{\~n}ano, {Jos{\'e} A.} and Mar{\'i}n-Mart{\'i}nez, {Juana M.} and Herranz-Mar{\'i}n, {M. Teresa} and Enrique Bernal-Morell and Josefina Garc{\'i}a-Garc{\'i}a and {de Dios Gonz{\'a}lez-Caballero}, Juan and Chirlaque-L{\'o}pez, {M. Dolores} and Alfredo Minguela-Puras and Manuel Muro-Amador and Antonio Moreno-Doc{\'o}n and Genoveva Yag{\"u}e-Guirao and Abell{\'a}n-Perpi{\~n}{\'a}n, {Jos{\'e} M.} and Mart{\'i}nez-P{\'e}rez, {Jorge E.} and S{\'a}nchez-Mart{\'i}nez, {Fernando I.} and Alberto Utrero-Rico and Mario Fern{\'a}ndez-Ruiz and Octavio Carretero and Aguado, {Jos{\'e} Mar{\'i}a} and Rocio Laguna-Goya and {\'A}ngel Jim{\'e}nez and Abi{\'a}n, {Mar{\'i}a Herrera} and Salmones, {Mercedes Garc{\'i}a} and Alarcon, {Lidia Gagliardi} and Oliveira, {Mar{\'i}a Rubio} and Romero, {Carlos Fabian Casta{\~n}o} and Cosgaya, {Carlos Aranda} and Palomares, {Virginia V{\'i}ctor} and Rodr{\'i}guez, {Leticia Garc{\'i}a} and Abad, {Maria Sanchez Carpintero} and Torrej{\'o}n, {Mª Carmen Garc{\'i}a}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2022.",

year = "2022",

month = dec,

doi = "10.1038/s41598-022-14035-x",

language = "English",

volume = "12",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

López-Rodríguez, R, Del Pozo-Valero, M, Corton, M, Minguez, P, Ruiz-Hornillos, J, Pérez-Tomás, ME, Barreda-Sánchez, M, Mancebo, E, Villaverde, C, Núñez-Moreno, G, Romero, R, Paz-Artal, E, Guillén-Navarro, E, Almoguera, B, Ayuso, C, Fernández-Caballero, L, Fernández Sanchez, R, García Vara, I, Marzal Gordo, L, Martinez-Ramas, A, Ondo, L, Górgolas, M, Cabello, A, Barba, GP, Heili, S, Calvo, C, Ríos, MDM, Santos, A, Sánchez-Pernaute, O, Llanos, L, Zazo, S, Rojo, F, Villar, F, de Andrés, R, Alfaro, IJ, Gadea, I, Perales, C, Juarez, YC, Mahillo, I, Herrero, A, Taracido, JC, García-Vázquez, E, Jara-Rubio, R, Pons-Miñano, JA, Marín-Martínez, JM, Herranz-Marín, MT, Bernal-Morell, E, García-García, J, de Dios González-Caballero, J, Chirlaque-López, MD, Minguela-Puras, A, Muro-Amador, M, Moreno-Docón, A, Yagüe-Guirao, G, Abellán-Perpiñán, JM, Martínez-Pérez, JE, Sánchez-Martínez, FI, Utrero-Rico, A, Fernández-Ruiz, M, Carretero, O, Aguado, JM, Laguna-Goya, R, Jiménez, Á, Abián, MH, Salmones, MG, Alarcon, LG, Oliveira, MR, Romero, CFC, Cosgaya, CA, Palomares, VV, Rodríguez, LG, Abad, MSC & Torrejón, MCG 2022, 'Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID-19', Scientific Reports, vol. 12, no. 1, 10369. https://doi.org/10.1038/s41598-022-14035-x

TY - JOUR

T1 - Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID-19

AU - López-Rodríguez, Rosario

AU - Del Pozo-Valero, Marta

AU - Corton, Marta

AU - Minguez, Pablo

AU - Ruiz-Hornillos, Javier

AU - Pérez-Tomás, María Elena

AU - Barreda-Sánchez, María

AU - Mancebo, Esther

AU - Villaverde, Cristina

AU - Núñez-Moreno, Gonzalo

AU - Romero, Raquel

AU - Paz-Artal, Estela

AU - Guillén-Navarro, Encarna

AU - Almoguera, Berta

AU - Ayuso, Carmen

AU - Fernández-Caballero, Lidia

AU - Fernández Sanchez, Ruth

AU - García Vara, Inés

AU - Marzal Gordo, Laura

AU - Martinez-Ramas, Andrea

AU - Ondo, Lorena

AU - Górgolas, Miguel

AU - Cabello, Alfonso

AU - Barba, Germán Peces

AU - Heili, Sara

AU - Calvo, César

AU - Ríos, María Dolores Martín

AU - Santos, Arnoldo

AU - Sánchez-Pernaute, Olga

AU - Llanos, Lucía

AU - Zazo, Sandra

AU - Rojo, Federico

AU - Villar, Felipe

AU - de Andrés, Raimundo

AU - Alfaro, Ignacio Jiménez

AU - Gadea, Ignacio

AU - Perales, Celia

AU - Juarez, Yolanda Cañadas

AU - Mahillo, Ignacio

AU - Herrero, Antonio

AU - Taracido, Juan Carlos

AU - García-Vázquez, Elisa

AU - Jara-Rubio, Rubén

AU - Pons-Miñano, José A.

AU - Marín-Martínez, Juana M.

AU - Herranz-Marín, M. Teresa

AU - Bernal-Morell, Enrique

AU - García-García, Josefina

AU - de Dios González-Caballero, Juan

AU - Chirlaque-López, M. Dolores

AU - Minguela-Puras, Alfredo

AU - Muro-Amador, Manuel

AU - Moreno-Docón, Antonio

AU - Yagüe-Guirao, Genoveva

AU - Abellán-Perpiñán, José M.

AU - Martínez-Pérez, Jorge E.

AU - Sánchez-Martínez, Fernando I.

AU - Utrero-Rico, Alberto

AU - Fernández-Ruiz, Mario

AU - Carretero, Octavio

AU - Aguado, José María

AU - Laguna-Goya, Rocio

AU - Jiménez, Ángel

AU - Abián, María Herrera

AU - Salmones, Mercedes García

AU - Alarcon, Lidia Gagliardi

AU - Oliveira, María Rubio

AU - Romero, Carlos Fabian Castaño

AU - Cosgaya, Carlos Aranda

AU - Palomares, Virginia Víctor

AU - Rodríguez, Leticia García

AU - Abad, Maria Sanchez Carpintero

AU - Torrejón, Mª Carmen García

PY - 2022/12

Y1 - 2022/12

N2 - Rare variants affecting host defense against pathogens could be involved in COVID-19 severity and may help explain fatal outcomes in young and middle-aged patients. Our aim was to report the presence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected group of COVID-19 patients under 65 years who required intubation or resulting in death (n = 44). To this end, different etiopathogenic mechanisms were explored using gene prioritization-based analysis in which genes involved in immune response, immunodeficiencies or blood coagulation were studied. We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic and were located in genes mainly involved in immune response. A network analysis, including the 42 genes with candidate variants, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks composed by genes enriched in carbohydrate metabolism and in DNA metabolism and repair processes. In conclusion, we have detected candidate variants that may potentially influence COVID-19 outcome in our cohort of patients. Further studies are needed to confirm the ultimate role of the genetic variants described in the present study on COVID-19 severity.

AB - Rare variants affecting host defense against pathogens could be involved in COVID-19 severity and may help explain fatal outcomes in young and middle-aged patients. Our aim was to report the presence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected group of COVID-19 patients under 65 years who required intubation or resulting in death (n = 44). To this end, different etiopathogenic mechanisms were explored using gene prioritization-based analysis in which genes involved in immune response, immunodeficiencies or blood coagulation were studied. We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic and were located in genes mainly involved in immune response. A network analysis, including the 42 genes with candidate variants, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks composed by genes enriched in carbohydrate metabolism and in DNA metabolism and repair processes. In conclusion, we have detected candidate variants that may potentially influence COVID-19 outcome in our cohort of patients. Further studies are needed to confirm the ultimate role of the genetic variants described in the present study on COVID-19 severity.

UR - http://www.scopus.com/inward/record.url?scp=85132267240&partnerID=8YFLogxK

U2 - 10.1038/s41598-022-14035-x

DO - 10.1038/s41598-022-14035-x

M3 - Article

C2 - 35725860

AN - SCOPUS:85132267240

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 10369

ER -

Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID-19

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