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

Amoxicillin-Resistant Streptococci Carriage in the Mouths of Children: A Systematic Review and Meta-Analysis

Streptococcal bacteremia that occurs during invasive dental procedures can lead to infective endocarditis (IE) in children with certain heart diseases. Prior to such procedures, antibiotic prophylaxis (AP) with amoxicillin (AMPC) is recommended. However, the detection of amoxicillin-resistant strains (AMPC-RS) in the mouths of children with heart diseases raises the concern that they would be uncovered by the action of standard AP. This work carried out a systematic review and meta-analysis regarding AMPC-RS carriage in the mouths of children. We consulted databases covering studies between the years 2000 and 2021, following the PRISMA declaration. A meta-analysis was carried out to assess the prevalence of children carrying AMPC-RS in the mouths. The antimicrobial tests were carried out by microdilution (46.2% of articles), disk diffusion (38.3%), and the E-test (15.4%). Streptococcus mitis and S. sanguinis were bacteria with the most found resistance phenotype, with MIC reaching values of 128 µg/mL. Of the 13 selected articles, only 6 presented results that made it possible to calculate the prevalence of children carrying AMPC-RS in their mouths, ranging from 5.5% to 86.3%. Most of the studies were classified as high quality, and the collected data demonstrate the presence of streptococcal strains with different levels of resistance in the collected samples, such as the dental plaque. The meta-analysis pointed to evidence of AMPC-RS being carried, with a prevalence of 21.3% (I² = 0%, p = 0.705). There is an important prevalence of AMPC-RS carriage in the mouths of children. Specific attention should be directed to AP in those susceptible to IE

BMP6 and VDR gene polymorphisms are associated with osteonecrosis in a sickle cell anaemia cohort

The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18–0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34–0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02–0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.</p