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

Reactivity of TpMe2Ir(C2H4)(DMAD) with carboxylic acids. A DFT study on geometrical isomers and structural characterization

The thermally unstable adduct TpMe2Ir(C2H4)(DMAD), which was generated “in situ” by the reaction of DMAD with TpMe2Ir(C2H4)2 (1) at low temperature, reacted with different carboxylic acids to produce the following compounds: TpMe2Ir(E-C(CO2Me)double bond; length as m-dashCH(CO2Me))(H2O)(OC(O)C6H4R), (R = H, 2a; o-OH, 2b; o-Cl, 2c; m-Cl, 2d; o-NO2, 2e; m-NO2, 2f;o-Me, 2g;p-Me, 2h) and TpMe2Ir(E-C(CO2Me)double bond; length as m-dashCH(CO2Me))(H2O)(OC(O)Me) 3. In the reaction of derivative 2a with Lewis bases, TpMe2Ir(E-C(CO2Me)double bond; length as m-dashCH(CO2Me))(L)(OC(O)C6H5), (L = Py, 4a; m-Br–Py, 4b; m-Cl–Py, 4c; NCMe, 5) were obtained, of which 4b and 4c were isolated as a mixture of two isomers in which the substituted pyridine ring was present at different rotational orientations. All new compounds prepared were characterized by 1H and 13C{1H} NMR spectroscopy, the structure of compounds 2d, 2h and 4a being determined by X-ray diffraction analysis. DFT was used to analyze the relative stability and the structural orientation of the isomers.CCDC 768172, 768174 and 768173 contain the supplementary crystallographic data for 2d, 2h and 4a. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Also, all NMR spectra including 1-D, 2-D heteronuclear experiments and long range bond correlations are available for this article from the author.Peer Reviewe