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

Acellular human corneal matrix sheets seeded with human adipose-derived mesenchymal stem cells integrate functionally in an experimental animal model

Purpose: To evaluate the in vivo biocompatibility of grafts composed of sheets of decellularized human corneal stroma with or without the recellularization of human adipose derived adult stem cells (h-ADASC) into the rabbit cornea. Methods: Sheets of human corneal stroma of 90 gm thickness were decellularized, and their lack of cytotoxicity was assayed. The recellularization was achieved by the injection of 2 x 10(5) labeled h-ADASC in the graft followed by five days of cell culture. The grafts were implanted in vivo into a stromal pocket at 50% depth. After a triple-masked three-month follow-up, the animals were euthanized and the bio-integration of the graft, the viability of the stem cells and the expression of keratocan (human keratocyte-specific protein) were assessed. Results: The decellularized stromal sheets showed an intact extracellular matrix with a decellularization rate of 92.8% and an excellent recellularization capacity in vitro with h-ADASC. A complete and stable graft transparency was observed during the full follow-up, with absence of any clinical sign of rejection. The postmortem analysis demonstrated the survival of the transplanted human stem cells inside the graft and their differentiation into functional keratocytes, as assessed by the expression of human keratocan. Conclusions: We report a new model of lamellar keratoplasty that requires only a simple and safe procedure of liposuction and a donor allogeneic cornea to provide an optically transparent autologous stromal graft with excellent biocompatibility and integration into the host tissue in a rabbit modelThis work was supported in part by grants CEN-20091021 from the Spanish Ministry of Health, IAP-560610-2008-44 and SAF2010-19230 from the Spanish Ministry of Science and Innovation, and from Fundacio Marato de TV3, Spain

Clinical Characteristics and Risk Factors of Respiratory Failure in a Cohort of Young Patients Requiring Hospital Admission with SARS-CoV2 Infection in Spain: Results of the Multicenter SEMI-COVID-19 Registry.

Age is a risk factor for COVID severity. Most studies performed in hospitalized patients with SARS-CoV2 infection have shown an over-representation of older patients and consequently few have properly defined COVID-19 in younger patients who require hospital admission. The aim of the present study was to analyze the clinical characteristics and risk factors for the development of respiratory failure among young (18 to 50 years) hospitalized patients with COVID-19. This retrospective nationwide cohort study included hospitalized patients from 18 to 50 years old with confirmed COVID-19 between March 1, 2020, and July 2, 2020. All patient data were obtained from the SEMI-COVID Registry. Respiratory failure was defined as the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) ≤200 mmHg or the need for mechanical ventilation and/or high-flow nasal cannula or the presence of acute respiratory distress syndrome. During the recruitment period, 15,034 patients were included in the SEMI-COVID-19 Registry, of whom 2327 (15.4%) were younger than 50 years. Respiratory failure developed in 343 (14.7%), while mortality occurred in 2.3%. Patients with respiratory failure showed a higher incidence of major adverse cardiac events (44 (13%) vs 14 (0.8%), p320 U/I (OR, 1.69; 95% CI, 1.18 to 2.42; p=0.0039), AST >35 mg/dL (OR, 1.74; 95% CI, 1.2 to 2.52; p=0.003), sodium 35 mg/dL (OR, 1.74; 95% CI, 1.2 to 2.52; p=0.003), sodium 8 mg/dL (OR, 2.42; 95% CI, 1.72 to 3.41; p Young patients with COVID-19 requiring hospital admission showed a notable incidence of respiratory failure. Obesity, SAHS, alcohol abuse, and certain laboratory parameters were independently associated with the development of this complication. Patients who suffered respiratory failure had a higher mortality and a higher incidence of major cardiac events, venous thrombosis, and hospital stay

Estimation of Admission D-dimer Cut-off Value to Predict Venous Thrombotic Events in Hospitalized COVID-19 Patients: Analysis of the SEMI-COVID-19 Registry.

Venous thrombotic events (VTE) are frequent in COVID-19, and elevated plasma D-dimer (pDd) and dyspnea are common in both entities. To determine the admission pDd cut-off value associated with in-hospital VTE in patients with COVID-19. Multicenter, retrospective study analyzing the at-admission pDd cut-off value to predict VTE and anticoagulation intensity along hospitalization due to COVID-19. Among 9386 patients, 2.2% had VTE: 1.6% pulmonary embolism (PE), 0.4% deep vein thrombosis (DVT), and 0.2% both. Those with VTE had a higher prevalence of tachypnea (42.9% vs. 31.1%; p = 0.0005), basal O2 saturation 1.0 μg/ml treated with prophylactic dose (p 2.0 μg/ml treated with intermediate dose (p = 0.0001), and 31.3% for those with pDd >3.0 μg/ml and full anticoagulation (p = 0.0183). In hospitalized patients with COVID-19, a pDd value greater than 3.0 μg/ml can be considered to screen VTE and to consider full-dose anticoagulation