Clonal 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 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

Estudio de cohortes en atención primaria sobre la evolución de sujetos con prediabetes (PREDAPS): Fundamentos y metodología

The PREDAPS study aims to determine the risk of developing diabetes and the risk of vascular complications in patients with prediabetes and identify factors associated with those risks. It is a prospective observational study of a cohort of 1184 subjects with prediabetes and another cohort of 838 subjects with no alterations in glucose metabolism. The data at baseline were obtained from patients attending primary care centers in Spain throughout 2012. Subjects with prediabetes were classified into three groups: those who had only altered the fasting blood glucose levels -between 100 and 125mg/dl-, those who had only altered the HbA1c level -between 5.7 and 6.4% - and those who had altered both parameters. Information on sociodemographic characteristics, personal and family history, lifestyle and drug therapy was obtained from medical records and the interview with the doctor in the consultation. It was also performed a physical examination to determine weight, height, waist circumference and blood pressure were performed and blood and urine analysis. The PREDAPS study may help to reduce uncertainty in individual prevention strategies in subjects with prediabetes. Annual monitoring of patients recruited for five years will enable to know the risk of developing diabetes type 2 and the risk of macro-and microvascular complications in the three groups of subjects with prediabetes and determine the factors associated with those risks.El estudio PREDAPS pretende determinar el riesgo de desarrollo de diabetes y aparición de complicaciones vasculares en sujetos con prediabetes e identificar los factores asociados. Se trata de un estudio observacional de seguimiento de una cohorte de 1.184 sujetos con prediabetes y otra cohorte de 838 sujetos sin alteraciones en el metabolismo de la glucosa. Los datos de la etapa basal se obtuvieron de pacientes que acudieron a centros de Atención Primaria en España a lo largo del año 2012. Los sujetos con prediabetes fueron clasificados en tres grupos: aquellos que sólo tenían alteradas las cifras de glucemia en ayunas -entre 100 y 125 mg/dl-, aquellos que sólo tenían alterado el nivel de HbA1c -entre 5,7 y 6,4%- y aquellos que tenían alterados ambos parámetros. La información sobre sus características sociodemográficas, antecedentes familiares y personales, estilos de vida y tratamiento farmacológico se obtuvo de la historia clínica y de la entrevista realizada en la consulta por el médico. Se realizó un examen físico para determinar peso, talla, perímetro de la cintura y presión arterial y se realizaron análisis de sangre y orina. El estudio PREDAPS puede contribuir a disminuir la incertidumbre en las estrategias individuales de prevención en los sujetos con prediabetes. El seguimiento anual durante cinco años de los participantes posibilitará conocer el riesgo de desarrollo de diabetes mellitus tipo 2 y el de complicaciones macro y microvasculares en los tres grupos de sujetos con prediabetes, así como averiguar los posibles factores asociados a esos riesgos