Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
Pérez-Jurado, Luís A. (Universitat Pompeu Fabra)
Cáceres, Alejandro (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (Barcelona))
Balagué Dobón, Laura (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (Barcelona))
Esko, Tõnu (Program in Medical and Population Genetics (Barcelona))
López de Heredia, Miguel (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Quintela, Inés
Cruz, Raquel (Universidade de Santiago de Compostela)
Lapunzina, Pablo (Hospital Universitario La Paz (Madrid))
Carracedo, Ángel (Fundación Pública Galega de Medicina Xenómica)
González, Juan Ramón (Universitat Autònoma de Barcelona. Departament de Matemàtiques)
SCOURGE Cohort Group

Date:	2024
Abstract:	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.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1974 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-801 Agencia Estatal de Investigación RTI2018-100789-B-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Aged ; Aging ; Chromosomes, Human, Y ; COVID-19 ; Humans ; Male ; Mosaicism ; SARS-CoV-2
Published in:	Communications Biology, Vol. 7 Núm. 1 (december 2024) , p. 202, ISSN 2399-3642

DOI: 10.1038/s42003-024-05805-6
PMID: 38374351

14 p, 3.8 MB

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