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

Clinicopathological characterization and genomic sequence differences observed in a highly virulent fowl <i>Aviadenovirus</i> serotype 4

<p>Highly virulent fowl aviadenoviruses (genus: <i>Aviadenovirus</i>) represent a significant risk in poultry farming that may contribute to increased mortality rates and may adversely affect the growth performance of poultry flocks. In this study, we performed the clinicopathological characterization of a FAdV strain SHP95 isolated from a commercial farm and its whole genome sequencing. The study revealed that the isolated strain is a highly virulent serotype 4 FAdV that can cause 100% mortality in day-old specific pathogen free (SPF) chickens with a dose of 2.5 × 10⁵ TCID₅₀. At a lower viral dose (1.5 × 10⁴ TCID₅₀), the infection in day-old SPF chickens caused 40% mortality and lesions characteristic for Hepatitis-hydropericardium syndrome (HHS). The viral strain was detectable by real time PCR in chicken organs, including the lymphoid organs until day 28 after infection. The whole genome assembly of strain SHP95 revealed a size of 45,641 bp, which encodes for 42 viral open reading frame (ORF). The comparative analysis in the genome shows 98.1% similarity between strain SHP95 and other FAdV-4 genomes reported. The major differences in the genome sequence between pathogenic and non-pathogenic fowl Adenovirus were identified in the right arm of the genome.</p