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00925njm 22002777a 4500 dc Pérez-Jurado, Luis Alberto author Cáceres, Alejandro author Balagué-Dobón, Laura author Esko, Tonu author López de Heredia, Miguel author Quintela, Inés author Cruz, Raquel author Lapunzina, Pablo author Carracedo, Ángel author SCOURGE Cohort Group author González, Juan R author Meijome, Xose M author Brochado-Kith, Oscar author Ceballos, Francisco C author Fernandez-Rodriguez, Amanda author Jimenez-Sousa, Maria Angeles author Martin-Vicente, Maria author Resino, Salvador author Virseda-Berdices, Ana author 2024-02-19 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. Commun Biol. 2024 Feb 19;7(1):202. 10.1038/s42003-024-05805-6 2399-3642 Communications biology 38374351 http://hdl.handle.net/20.500.12105/19094 Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2