Two of the most common bacterial skin infections of young infants and children are bullous impetigo due to Staphylococcus aureus and its more acute form, staphylococcal scalded skin syndrome. Epidermolysin A (ETA), ETB and, possibly, ETD are responsible for these diseases, which may appear as epidemics in pediatric patients. We tested the reliability of a flow cytometry-assisted multiplex immunoassay (Bio-Plex system) for the detection of ETA and ETB. The Bio-Plex system was found to be highly specific and highly sensitive for toxin concentrations of between 2 and 80,000 pg/ml. The results of this assay were 100% identical to the results of a PCR-based method. We demonstrated that this test did not generate any cross-reactions with ETD-producing isolates. The level of detection of ETB by this test differed according to culture conditions and from isolate to isolate; these results must be taken into account for diagnostic purposes.Impetigo accounts for 10% of bacterial skin infections in neonates and young children. About 30% of children with impetigo develop bullous impetigo due to Staphyloccocus aureus (15). Children 7 years old and younger, adults with renal failure, and immunosuppressed adults may develop a generalized form of bullous impetigo called staphylococcal scalded skin syndrome. These two diseases are caused by strains of S. aureus that produce exfoliative toxins (ETs) or epidermolysins (epidermolysin A [ETA] and ETB). Three epidermolysins have been characterized: these include ETA (2), ETB (13), and ETD (30). These toxins are able to split the superficial epidermis by cleaving the desmosomes of the granular cell layer. This splitting exposes patients to secondary infections by opportunistic pathogens (15). ETs are serine proteases that specifically target and cleave Dsg1 (1). Dsg1 is a member of the desmosomal cadherin family, which includes desmogleins and desmocollins. These molecules are essential for the proper functioning of desmosomes, which maintain the integrity of epithelial tissues. ETs cleave Dsg1 in one of its calcium-binding domains. The three toxins hydrolyze the peptide bond after the glutamic acid at position 381, which forms part of a specific sequence located between extracellular domains 3 and 4.Samples from infected patients are frequently sent to laboratories for analysis, and the detection of epidermolysins is essential to limit the risks of colonization or spreading in pediatric hospital departments.A flow cytometry-assisted multiplex particle-based immunoassay (Bio-Plex system; Bio-Rad, Hercules, Calif.) has been designed and may be used to characterize bacterial compounds and toxins (9, 22). The Bio-Plex technology (8) consists of a particle counter and two laser beams (hardware) as well as software that allows the simultaneous discrimination of beads of different colors and the recording of phycoerythrin-generated fluorescence associated with the beads. One hundred different colors can be distinguished, making it theoretically possible to quantify 100 proteins or ligands si...

MAS825, a bispecific IL-1⍰/IL-18 monoclonal antibody, could improve clinical outcomes in COVID19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized nonventilated patients with COVID-19 pneumonia (n=138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on day of discharge (whichever was earlier) with worst case imputation for death. Other study endpoints included safety, Creactive protein (CRP), SARS-CoV2 presence and inflammatory markers. On Day 15, the APACHE II score was 14.5±1.87 and 13.5±1.8 in the MAS825 and placebo groups, respectively (P=0.33). MAS825 + SoC led to 33% relative reduction in intensive care unit (ICU) admissions, ~1 day reduction in ICU stay, reduction in mean duration of oxygen support (13.5 versus 14.3 days) and earlier clearance of virus on Day 15 versus placebo + SoC group. On Day 15, compared with placebo group, patients treated with MAS825 + SoC showed a 51% decrease in CRP levels, 42% lower IL-6 levels, 19% decrease in neutrophil levels and 16% lower interferon-γ levels, indicative of IL-1β and IL-18 pathway engagement. MAS825 + SoC did not improve APACHE II score in hospitalized patients with severe COVID19 pneumonia; however, it inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance versus placebo + SoC. MAS825 used in conjunction with SoC was well tolerated. None of the adverse events (AEs) or serious AEs were treatment-related.