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

Pseudomorphic Replacement of Mg–Ca Carbonates after Gypsum and Anhydrite

In this paper, we present a comparative study of the pseudomorphic carbonatation of gypsum and anhydrite single crystals in Mg-bearing aqueous solutions at room temperature. We have found that carbonatation of gypsum an anhydrite occurs via a similar coupled dissolution–crystallization mechanism. However, whereas pseudomorphization of anhydrite precisely preserves the external form and dimension of the initial crystals, pseudomorphs after gypsum are less perfect and the shape and volume of the original crystals are partially lost. Furthermore, the mineralogical compositions of the pseudomorphs after anhydrite and gypsum are different, because gypsum is replaced by relatively large calcite crystals, while anhydrite pseudomorphs consist of aggregates of calcite and aragonite. Such textural and compositional differences can be clearly related to the length scale of the coupling between dissolution and crystallization at the replacement fronts. In situ atomic force microscopy observations of the early stages of carbonatation have shown that dissolution and crystallization are very tightly coupled on anhydrite rather than on gypsum surfaces. This clearly indicates that during the replacement of anhydrite and gypsum, dissolution and precipitation, respectively, are the rate-limiting steps. On the other hand, the higher supersaturation levels reached during the replacement of anhydrite lead to a competition between calcite and aragonite crystallization. This explains the fact that calcite and aragonite coexist within the replacement layers after anhydrite. Finally, we have found that dissolved magnesium in the reacting solutions is almost equally incorporated into the pseudomorphs, regardless of both the precursor phase and the mineralogical composition of the replacements. Our calculations and chemical analyses have shown that the compositions of the MgxCa1–xCO3 solid solution for which supersaturations reach maximum values correspond quite well with maximum Mg/Ca ratios in the replacement layers.This work was supported by the Spanish Government (MAT2012-38810 and CGL2013-48247-P). AFM and SEM images, and EDX analyses were obtained at the ICTS Centro Nacional de Microscopia Electrónica-UCM. We thank Ana Vicente for assistance with the SEM. GIXRD patterns were recorded at the X-ray Diffraction Central Service-UCM. We also thank Ignacio Carabias for technical support and valuable help in GIXRD interpretation. C.P. is grateful to the Spanish Government for a FPU Fellowship.Peer reviewe