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

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dc.contributor.authorPérez-Jurado, Luis Alberto
dc.contributor.authorCáceres, Alejandro
dc.contributor.authorBalagué-Dobón, Laura
dc.contributor.authorEsko, Tonu
dc.contributor.authorLópez de Heredia, Miguel
dc.contributor.authorQuintela, Inés
dc.contributor.authorCruz, Raquel
dc.contributor.authorLapunzina, Pablo
dc.contributor.authorCarracedo, Ángel
dc.contributor.authorSCOURGE Cohort Group
dc.contributor.authorGonzález, Juan R
dc.contributor.authorMeijome, Xose M
dc.contributor.authorBrochado-Kith, Oscar
dc.contributor.authorCeballos, Francisco C
dc.contributor.authorFernandez-Rodriguez, Amanda
dc.contributor.authorJimenez-Sousa, Maria Angeles
dc.contributor.authorMartin-Vicente, Maria
dc.contributor.authorResino, Salvador
dc.contributor.authorVirseda-Berdices, Ana
dc.contributor.funderGovernment of Catalonia (España)
dc.contributor.funderMinisterio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
dc.contributor.funderEstonian Research Counciles_ES
dc.contributor.funderInstituto de Salud Carlos III
dc.contributor.funderAmancio Ortega Foundationes_ES
dc.contributor.funderBanco Santander
dc.date.accessioned2024-04-01T07:57:20Z
dc.date.available2024-04-01T07:57:20Z
dc.date.issued2024-02-19
dc.description.abstractThe 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.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipWe thank Gemma Moncunill, Lluís 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 María 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.es_ES
dc.format.number1es_ES
dc.format.page202es_ES
dc.format.volume7es_ES
dc.identifier.citationCommun Biol. 2024 Feb 19;7(1):202.es_ES
dc.identifier.doi10.1038/s42003-024-05805-6es_ES
dc.identifier.e-issn2399-3642es_ES
dc.identifier.journalCommunications biologyes_ES
dc.identifier.pubmedID38374351es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/19094
dc.language.isoenges_ES
dc.publisherNature Publishing Group
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/MINECO//MDM-2014-0370/ES/DPTO. CIENCIAS EXPERIMENTALES Y DE LA SALUD/es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/CEX2018-000806-Ses_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/COV20_00622es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/RTI2018-100789-B-I00es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s42003-024-05805-6es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiología (CNM)es_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshSARS-CoV-2es_ES
dc.subject.meshCOVID-19es_ES
dc.subject.meshMalees_ES
dc.subject.meshHumanses_ES
dc.subject.meshAgedes_ES
dc.subject.meshMosaicismes_ES
dc.subject.meshChromosomes, Human, Yes_ES
dc.subject.meshAginges_ES
dc.titleClonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2es_ES
dc.typeresearch articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
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