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

Successful pharmaco-invasive approach using a lower alteplase dose and VA-ECMO support in high-risk pulmonary embolism: case report

Despite the elevated mortality rates associated with high-risk pulmonary embolism (PE), this condition remains understudied. Data regarding the effectiveness and safety of invasive therapies such as venoarterial extracorporeal membrane oxygenation (VA-ECMO) in this patient population remains controversial. Here, we present the case of a 61-year-old male with high-risk PE associated with refractory cardiac arrest and cardiogenic shock who underwent a combination of extracorporeal cardiopulmonary resuscitation with VA-ECMO and pharmaco-invasive therapy (mechanical thrombi fragmentation plus lower alteplase dose), resulting in successful pulmonary reperfusion. After a prolonged in-hospital stay, the patient was discharged in stable condition