High fetal hemoglobin level is associated with increased risk of cerebral vasculopathy in children with sickle cell disease in Mayotte.

BACKGROUND: Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia, specific to each population, would be prognostically useful and could inform personalized therapeutics.The objective of this study was to describe the genetic modulators of sickle cell disease in a cohort of pediatric patients followed up in Mayotte. METHODS: This retrospective cohort study analyzed clinical and biological data, collected between January1st2007 and December 31st2017, in children younger than 18 years. RESULTS: We included 185 children with 72% SS, 16% Sß0-thalassemia and 12% Sß + thalassemia. The average age was 9.5 years; 10% of patients were lost to follow up. The Bantu haplotype was associated with an increase in hospitalizations and transfusions. The alpha-thalassemic mutation was associated with a decrease of hemolysis biological parameters (anemia, reticulocytes), and a decrease of cerebral vasculopathy. The Single Nucleotide Polymorphisms BCL11A rs4671393, BCL11A rs11886868, BCL11A rs1427407 and HMIP rs9399137 were associated with the group of children with HbF > 10%. Patients with HbF > 10% presented a significant risk of early onset of cerebral vasculopathy. CONCLUSIONS: The most remarkable result of our study was the association of SNPs with clinically relevant phenotypic groups. BCL11A rs4671393, BCL11A rs11886868, BCL11A rs1427407 and HMIP rs9399137 were correlated with HbF > 10%, a group that has a higher risk of cerebral vasculopathy and should be oriented towards the hemolytic sub-phenotype.

Characteristics and outcomes of SARS-COV 2 critically ill patients after emergence of the variant of concern 20H/501Y.V2: A comparative cohort study.

There are currently no data regarding characteristics of critically ill patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant of concern (VOC) 20H/501Y.V2. We therefore aimed to describe changes of characteristics in critically ill patients with Covid-19 between the first and the second wave when viral genome sequencing indicated that VOC was largely dominant in Mayotte Island (Indian Ocean). Consecutive patients with Covid-19 and over 18 years admitted in the unique intensive care unit (ICU) of Mayotte during wave 2 were compared with an historical cohort of patients admitted during wave 1. We performed a LR comparing wave 1 and wave 2 as outcomes. To complete analysis, we built a Random Forest model (RF), that is, a machine learning classification tool- using the same variable set as that of the LR. We included 156 patients, 41 (26.3%) and 115 (73.7%) belonging to the first and second waves respectively. Univariate analysis did not find difference in demographic data or in mortality. Our multivariate LR found that patients in wave 2 had less fever (absence of fever aOR 5.23, 95% confidence interval (CI) 1.89-14.48, p = .001) and a lower simplified acute physiology score (SAPS II) (aOR 0.95, 95% CI 0.91-0.99, p = .007) at admission; at 24 hours, the need of invasive mechanical ventilation was higher (aOR 3.49, 95% CI 0.98-12.51, p = .055) and pO2/FiO2 ratio was lower (aOR 0.99, 95 % CI 0.98-0.99, p = .03). Patients in wave 2 had also an increased risk of ventilator-associated pneumonia (VAP) (aOR 4.64, 95% CI 1.54-13.93, p = .006). Occurrence of VAP was also a key variable to classify patients between wave 1 and wave 2 in the variable importance plot of the RF model. Our data suggested that VOC 20H/501Y.V2 could be associated with a higher severity of respiratory failure at admission and a higher risk for developing VAP. We hypothesized that the expected gain in survival brought by recent improvements in critical care management could have been mitigated by increased transmissibility of the new lineage leading to admission of more severe patients. The immunological role of VOC 20H/501Y.V2 in the propensity for VAP requires further investigations.

Isotypic analysis of antibodies against activated Factor VII in patients with Factor VII deficiency using the x-MAP technology.

While the immune response to hemophilic factors in hemophilia has been widely studied, little is known about the development of anti-Factor VII (FVII) antibodies in FVII deficiency. We developed a robust technique based on the x-MAP technology to detect the presence of antibodies against FVII and characterize their isotype and validated this method using blood samples from 100 patients with FVII deficiency (median FVII clotting activity [FVII:C]: 6%) and 95 healthy controls. Anti-FVII antibodies were detected in patients but also in some controls, although the concentration of total immunoglobulin G (IgGt) and IgG1 and IgG4 subclasses was significantly different between groups. The IgG1 subclass concentrations remained significantly different also when only untreated patients were compared with controls. This difference could partially be related to the F7 genotype, particularly in patients harboring the p.Arg139Gln mutation. This x-MAP-based method might be useful for assessing the immunogenicity of novel FVII compounds and of activated FVII (FVIIa) concentrates. Further prospective studies are needed to better understand the clinical relevance of these antibodies in the management of patients with FVII deficiency.