Pérez Jurado, Luis A.Cáceres, AlejandroBalagué Dobón, LauraEsko, TonuLópez de Heredia, MiguelQuintela, InésCruz, RaquelLapunzina, PabloCarracedo, ÁngelSCOURGE Cohort GroupGonzález, Juan R.2024-05-152024-05-152024-02-192399-3642https://hdl.handle.net/2445/211324The 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.14 p.application/pdfengcc by (c) Pérez Jurado, Luis A. et al, 2024http://creativecommons.org/licenses/by/3.0/es/COVID-19Anomalies cromosòmiquesCOVID-19Chromosome abnormalitiesinfo:eu-repo/semantics/article2024-05-08info:eu-repo/semantics/openAccess38374351