biostudies-literatureUnknown7(1)Perez-Jurado LAThe 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 LOCommunications biology202https://www.ebi.ac.uk/biostudies/studies/S-EPMC10876565biostudies-literatureClonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2.PMC10876565de la Horra CAndreu-Bernabeu ALopez-Ruz MARodriguez-Urrego PACuesta LValencia-Ramos JBrion MDantas-Komatsu RCSRodriguez-Ferrer MRodriguez-Garcia JASouza VSRodriguez-Gallego CDiaz-Perez AMunoz Garcia PRodriguez-Novoa GEPadilla-Conejo IHorcajada JPMejuto-Montero NSantos ARuiz-Cubillan JJTeper AHeili-Frades SPariente-Rodriguez RSchluter AHerrero MJFernandez-Villa TTorres-Gutierrez RPMontoya JJBernal EMendez-Echevarria ALopez-Rodriguez RMoreno-Escalante JSanchez-Prados MCRubio CVillar FValido APerales CArnalich Fernandez FCamacho SSanchez-Carpintero Abad MVasconcelos RHTMartin-Fernandez MMartinez-Paz PMartinez-Ramas AMoreno RArcanjo ACPeces-Barba GFriaza VOrtiz-Flores 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GPInigo-Campos AMedeiros JFPHernandez-Moro CCardona-Huerta SCorton MJimenez PPerez-Matute PfalseClonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2.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 LO2024-01-01T00:00:00Z2024 Feb2026-06-02T22:44:22.439Z2025-04-19T07:37:50.693ZS-EPMC108765653837435110.1038/s42003-024-05805-6