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We thank Gemma Moncunill, Lluis Armengol and Jozef Gecz for their critical reading of initial versions of this manuscript. The authors acknowledge support from the Catalan Department of Economy and Knowledge (SGR2017/1974, SGR2017/801), the Spanish Ministry of Science Programa de Excelencia Maria de Maeztu (MDM-2014-0370) and Centro de Excelencia Severo Ochoa (CEX2018-000806-S), the Fondo Europeo de Desarrollo Regional, UE (RTI2018-100789-B-I00) and the Estonian Research Council (PUT1660). The SCOURGE study has been funded by Instituto de Salud Carlos III (COV20_00622) and ofounded by European Union (ERDF) A way of making Europe; additional funding was received from Amancio Ortega Foundation and Banco de Santander. Authors also receive support from the Generalitat de Catalunya through the CERCA Program.

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Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

Publicado en:Commun Biol. 7 (1): 202- - 2024-02-19 7(1), DOI: 10.1038/s42003-024-05805-6

Autores: Perez-Jurado, Luis A; Caceres, Alejandro; Balague-Dobon, Laura; Esko, Tonu; de Heredia, Miguel Lopez; Quintela, Ines; Cruz, Raquel; Lapunzina, Pablo; Carracedo, Angel; Abellan, Javier; Acosta-Isaac, Rene; Maria Aguado, Jose; Aguilar, Carlos; Aguilera-Albesa, Sergio; Ahmadi Sabbagh, Abdolah; Alba, Jorge; Albu, Sergiu; Alcala-Gallardo, Karla A M; Alcoba-Florez, Julia; Alcolea Batres, Sergio; Rafael Algarin-Lara, Holmes; Almadana, Virginia; Medeiros, Kelliane A; Almeida, Julia; Almoguera, Berta; Alonso, Maria R; Alvarez, Nuria; Alvarez-Sala Walther, Rodolfo; Alvarez-Benitez, Yady; Alvarez-Navia, Felipe; dos Santos, Katiusse A; Andreu-Bernabeu, Alvaro; Rosa Antonijoan, Maria; Martinez-Aquino, Eleno; Arana-Arri, Eunate; Aranda, Carlos; Arango, Celso; Araque, Carolina; Araujo, Nathalia K; Arcanjo, Ana C; Arnaiz, Ana; Arnalich Fernandez, Francisco; Arranz, Maria J; Arribas Lopez, Jose Ramon; Artiga, Maria-Jesus; Avello-Malaver, Yubelly; Ayuso, Carmen; Ballina Martin, Belen; Baptista-Rosas, Raul C; Maria Baldion, Ana; Barranco-Diaz, Andrea; Barreda-Sanchez, Maria; Barrera-Penagos, Viviana; Belhassen-Garcia, Moncef; Bernal-Bello, David; Bernal, Enrique; Bezerra, Joao F; Bezerra, Marcos A C; Blanca-Lopez, Natalia; Blancas, Rafael; Boix-Palop, Lucia; Borobia, Alberto; Bravo, Elsa; Brion, Maria; Brochado-Kith, Oscar; Brugada, Ramon; Bustos, Matilde; Cabello, Alfonso; Caceres-Agra, Juan J; Calbo, Esther; Calderon, Enrique J; Camacho, Shirley; Ceballos, Francisco C; Canadas, Yolanda; Carbonell, Cristina; Cardona-Huerta, Servando; Sanchez-Carpintero Abad, Maria; Carpio Segura, Carlos; Antonio Carrillo-Avila, Jose; Campos, Marcela C; Casasnovas, Carlos; Castano, Luis; Castano, Carlos F; Castelao, Jose E; Castellano Candalija, Aranzazu; Castillo, Maria A; Chaves-Santiago, Walter G; Chiquillo-Gomez, Sylena; Cid-Lopez, Marco A; Cienfuegos-Jimenez, Oscar; Conde-Vicente, Rosa; Cunha, Gabriela C R; Lourdes Cordero-Lorenzana, M; Corella, Dolores; Corrales, Almudena; Cortes-Sanchez, Jose L; Corton, Marta; Souza, Karla S C; Silva, Fabiola T C; Cuesta, Luisa; Tavares, Nathali A C; Carvalho, Maria C C; Dalmau, David; Dantas-Komatsu, Raquel C S; Teresa Darnaude, M; de Andres, Raimundo; de Juan, Carmen; de la Cruz Troca, Juan J; de la Horra, Carmen; de la Hoz, Ana B; De Martino-Rodriguez, Alba; Cruz, Marina S; de Sousa Alves Neri, Julianna Lys; del Campo-Perez, Victor; Delgado-Cuesta, Juan; Diaz de Bustamante, Aranzazu; Diaz-Perez, Anderson; Dietl, Beatriz; Diz-de Almeida, Silvia; Alves, Manoella do Monte; Dominguez-Garrido, Elena; Rosa, Lidia S; Luchessi, Andre D; Echave-Sustaeta, Jose; Eiros, Rocio; Enciso-Olivera, Cesar O; Escudero, Gabriela; Pablo Espana, Pedro; Estigarribia Sanabria, Gladys; Carmen Farinas, Maria; Fernandez, Ramon; Fernandez-Caballero, Lidia; Fernandez-Cruz, Ana; Fernandez-Ferrero, Silvia; Fernandez Martinez, Yolanda; Fernandez-Nestosa, Maria J; Fernandez-Robelo, Uxia; Fernandez-Rodriguez, Amanda; Fernandez-Sampedro, Marta; Fernandez, Ruth; Fernandez-Villa, Tania; Fernandez-Capitan, Carmen; Carioca, Antonio Augusto F; Flores-Perez, Patricia; Fuenmayor-Hernandez, Lacides; Fuertes-Nunez, Marta; Fumado, Victoria; Gadea, Ignacio; Gagliardi, Lidia; Gago-Dominguez, Manuela; Gallego, Natalia; Galoppo, Cristina; Garcia-Soidan, Ana; Garcia-Cerrada, Carlos; Garcia-de-Vicuna, Aitor; Garcia-Garcia, Josefina; Garcia-Garcia, Irene; Garcia-Ibarbia, Carmen; Garcia-Montero, Andres C; Garcia, Leticia; Garcia, Mercedes; Garcia Torrejon, Maria Carmen; Garcia, Ines; Garcia-Vazquez, Elisa; Garza-Frias, Emiliano; Gentile, Angela; Gil-Fournier, Belen; de Araujo, Jessica N G; Gomez-Duque, Mario; Gomez-Arrue, Javier; Gomez Carrera, Luis; Gomez Garcia, Maria; Gomez Sacristan, Angela; Gonzalez, Juan R; Gonzalez-Neira, Anna; Gonzalez Alvarez, Beatriz; Bernaldo de Quiros, Fernan Gonzalez; Gonzalez-Montelongo, Rafaela; Gonzalez-Penas, Javier; Gonzalez-Sagrado, Manuel; Gonzalo-Benito, Hugo; Gorgojo-Galindo, Oscar; Gorgolas, Miguel; Guaragna, Florencia; Chaux, Jessica G; Guillen-Navarro, Encarna; Guillen-Guio, Beatriz; Guisado-Vasco, Pablo; Gutierrez-Castaneda, Luz D; Gutierrez-Bautista, Juan F; Heili-Frades, Sara; Jacomo, Rafael H; Hernandez, Estefania; Hernandez-Moro, Cristina; Hernandez-Ortega, Luis D; Hernandez-Perez, Guillermo; Hernandez-Vaquero, Rebeca; Herraez, Belen; Teresa Herranz, M; Herrera, Maria; Jose Herrero, Maria; Herrero-Gonzalez, Antonio; Horcajada, Juan P; Imaz-Ayo, Natale; Intxausti-Urrutibeaskoa, Maider; Inigo-Campos, Antonio; Iniguez, Maria; Jara, Ruben; Jimenez, Angel; Jimenez-Alfaro, Ignacio; Jimenez, Pilar; Jimenez-Sousa, Maria A; Jordan, Iolanda; Laguna-Goya, Rocio; Laorden, Daniel; Lasa-Lazaro, Maria; Claudia Lattig, Maria; Lauriente, Ailen; Liger Borja, Anabel; Llanos, Lucia; Lopez-Bernus, Amparo; Lopez de Heredia, Miguel; Lopez-Garcia, Esther; Lopez-Granados, Eduardo; Lopez-Rodriguez, Rosario; Lopez-Ruz, Miguel A; Lorente, Leonardo; Lorenzo-Salazar, Josem; Lozano, Jose E; Lozano-Espinosa, Maria; Mahillo, Ignacio; Mancebo, Esther; Mar, Carmen; Marcelo Calvo, Cristina; Marcos-Delgado, Alba; Marcos, Miguel; Marin-Candon, Alicia; Mariscal-Aguilar, Pablo; Martin-Pedraza, Laura; Martin-Fernandez, Marta; Martin-Lopez, Caridad; Martin-Oterino, Jose-Angel; Dolores Martin, Maria; Martin, Vicente; Martin, Maria M; Martin-Vicente, Maria; Martinez, Amalia; Martinez-Gonzalez, Oscar; Martinez, Ricardo; Martinez-Paz, Pedro; Diaz-Caneja, Covadonga M; Martinez-Nieto, Oscar; Martinez-Lopez, Iciar; Martinez-Resendez, Michel F; Martinez, Silvia; Jose Martinez, Juan; Martinez-Perez, Angel; Martinez-Ramas, Andrea; Martinez-Robles, Violeta; Marzal, Laura; Mazzeu, Juliana F; Medrano, Francisco J; Meijome, Xose M; Mejuto-Montero, Natalia; Mendes, Ingrid; Duarte, Alice L; Mendez-Echevarria, Ana; Mendoza Charris, Humberto; Merayo Macias, Eleuterio; Mercadillo, Fatima; Mercado-Sesma, Arieh R; Minguez, Pablo; Molina-Roldan, Elena; Molina, AntonioJ J; Jose Montoya, Juan; Pinho, Susana M T; Moreira-Escriche, Patricia; Morelos-Arnedo, Xenia; Moreno, Rocio; Moreno Cuerda, Victor; Moreno-Docon, Antonio; Moreno-Escalante, Junior; Moreno Fernandez, Alberto; Munoz Garcia, Patricia; Neira, Pablo; Nevado, Julian; Nieto-Ganan, Israel; Silbiger, Vivian N; Nunez-Torres, Rocio; Obrador-Hevia, Antonia; Gonzalo Ocejo-Vinyals, J; Olivar, Virginia; Oliveira, Silviene F; Ondo, Lorena; Orfao, Alberto; Ortega-Paino, Eva; Ortega, Luis; Ortiz-Lopez, Rocio; Ortiz-Flores, Fernando; Oteo, Jose A; Pacheco, Manuel; Javier Pacheco-Miranda, Fredy; Padilla-Conejo, Irene; Panadero-Fajardo, Sonia; Parellada, Mara; Pariente-Rodriguez, Roberto; Friaza, Vicente; Paz-Artal, Estela; Peces-Barba, German; Pedromingo Kus, Miguel S; Perales, Celia; Santos, Ney P C; Guegel, Genilson P; Jazmin Perez, Maria; Perez, Alexandra; Perez-Matute, Patricia; Perez, Cesar; Perez-de-Nanclares, Gustavo; Perez-Garcia, Felipe; Perez, Patricia; Elena Perez-Tomas, M; Perucho, Teresa; Pichardo, Lisbeth A; Ribeiro, Adriana P; Pinsach-Abuin, Mel lina; Adriana Pinzon, Luz; Medeiros, Jeane F P; Pita, Guillermo; Pla-Junca, Francesc; Planas-Serra, Laura; Pompa-Mera, Ericka N; Porras-Hurtado, Gloria L; Pujol, Aurora; Eugenia Quevedo-Chavez, Maria; Angeles Quijada, Maria; Ramiro-Leon, Soraya; Rascado Sedes, Pedro; Nunes, Joana F R; Recalde, Delia; Recio-Fernandez, Emma; Resino, Salvador; Sousa, Renata R; Rivadeneira-Chamorro, Carlos S; Roa-Agudelo, Diana; Robelo Pardo, Montserrat; Fernandes, Marianne R; Rodriguez-Hernandez, Maria A; Rodriguez-Palmero, Agusti; Rodriguez-Ruiz, Emilio; Johanna Rodriguez, Marilyn; Rodriguez-Artalejo, Fernando; Rodriguez-Ferrer, Marena; Rodriguez-Gallego, Carlos; Rodriguez-Garcia, Jose A; Rodriguez Maya, Belen; Rodriguez-Nicolas, Antonio; Ezequiel Rodriguez-Novoa, German; Rodriguez-Urrego, Paula A; Rojo, Federico; Romero-Coronado, Andrea; Morilla, Ruben; Rondon-Garcia, Filomeno; Rosales-Castillo, Antonio; Rubio, Cladelis; Rubio Olivera, Maria; Ruiz-Cabello, Francisco; Ruiz-Casares, Eva; Ruiz-Cubillan, Juan J; Ruiz-Hornillos, Javier; Ruiz, Montserrat; Ryan, Pablo; Salamanca, Hector D; Salazar-Garcia, Lorena; Gabriela Salgueiro-Origlia, Giorgina; Sangil, Anna; Sanchez-Pernaute, Olga; Sanchez, Pedro-Luis; Sanchez Lopez, Antonio J; Sanchez-Pablo, Clara; Concepcion Sanchez-Prados, Maria; Sanchez-Real, Javier; Sanchez-Redondo, Jorge; Sancho-Sainz, Cristina; Sande, Esther; Santos, Arnoldo; Schluter, Agatha; Segovia, Sonia; Serra-Llovich, Alex; Sevil-Puras, Fernando; Sevilla-Porras, Marta; Sicolo, Miguel A; Silvan-Fuentes, Cristina; Moraes, Vitor M S; Souza, Vanessa S; Sole-Violan, Jordi; Manuel Soria, Jose; Sorli, Jose V; Silva, Nayara S; Carlos Souto, Juan; Sprockel, John J; Javier Suarez-Rama, Jose; Suarez-Zamora, David A; Taboada-Fraga, Xiana; Tamayo, Eduardo; Tamayo-Velasco, Alvaro; Carlos Taracido-Fernandez, Juan; Vasconcelos, Romero H T; Telleria, Carlos; Carratto, Thassia M T; Antonio Tenorio-Castano, Jair; Teper, Alejandro; Araujo, Izabel M T; Torres-Macho, Juan; Torres-Tobar, Lilian; Torres-Gutierrez, Ronald P; Troya, Jesus; Urioste, Miguel; Valencia-Ramos, Juan; Valido, Agustin; Pablo Vargas-Gallo, Juan; Varon, Belen; Vega, Tomas; Velasco-Quirce, Santiago; Velez-Santamaria, Valentina; Victor, Virginia; Vidan-Estevez, Julia; Silva, Gabriela V; Vieitez-Santiago, Miriam; Vilches, Carlos; Villalobos, Lavinia; Villar, Felipe; Villar-Garcia, Judit; Villaverde, Cristina; Villoslada-Blanco, Pablo; Virseda-Berdices, Ana; Costa, Tatiana X; Yanez, Zuleima; Zapatero-Gaviria, Antonio; Zarate, Ruth; Zazo, Sandra; Flores, Carlos; Riancho, Jose A; Rojas-Martinez, Augusto

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Resumen

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality.

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