Objective To characterize the demographic and clinical features of pediatric SARS-CoV-2 syndromes and identify admission variables predictive of disease severity. Study design We conducted a multicenter, retrospective and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at eight sites in New York, New Jersey, and Connecticut. Results We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into three groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% versus 18%, P =.02). Seven patients (2%) died and 114 (41%) were admitted to the ICU. In multivariable analyses, obesity (OR=3.39, 95% CI:1.26-9.10, P =.02) and hypoxia on admission (OR=4.01; 95% CI:1.14-14.15; P =.03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR=8.33 per unit decrease in 10 9 cells/L, 95% CI:2.32-33.33, P =.001) and higher C-reactive protein (OR=1.06 per unit increase in mg/dL, 95% CI:1.01-1.12, P =.017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity. Conclusions We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.

IMPORTANCE Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. OBJECTIVE To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. DESIGN, SETTING, AND PARTICIPANTS This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates;denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age-and month-specific multipliers accounting for underdetection of reported COVID-19 case counts.

Bacterial vaginosis is a highly prevalent and poorly understood polymicrobial disorder of the vaginal microbiota, with significant adverse sequelae. Gardnerella vaginalis predominates in bacterial vaginosis. Biofilms of G. vaginalis are present in human infections and are implicated in persistent disease, treatment failure, and transmission. Here we demonstrate that G. vaginalis biofilms contain extracellular DNA, which is essential to their structural integrity. Enzymatic disruption of this DNA specifically inhibits biofilms, acting on both newly forming and established biofilms. DNase liberates bacteria from the biofilm to supernatant fractions and potentiates the activity of metronidazole, an antimicrobial agent used in the treatment of bacterial vaginosis. Using a new murine vaginal colonization model for G. vaginalis, we demonstrate >10-fold inhibition of G. vaginalis colonization by DNase. We conclude that DNase merits investigation as a potential nonantibiotic adjunct to existing bacterial vaginosis therapies in order to decrease the risk of chronic infection, recurrence, and associated morbidities.

We undertook a cross-sectional survey of antimicrobial stewardship clinicians in North America and Australasia regarding practices, goals, and barriers to implementation of stewardship for pediatric oncology patients. Goals and barriers were similar regardless of clinician or institutional characteristics and geographic location. Strategies addressing these factors could help optimize antimicrobial use.

Background: Retrocyclins are cyclic antimicrobial peptides that have been shown to be both broadly active and safe in animal models. RC-101, a synthetic retrocyclin, targets important human pathogens and is a candidate vaginal microbicide. Its activity against microbes associated with bacterial vaginosis is unknown. Methods:We investigated the effect of RC-101 on toxin activity, bacterial growth and biofilm formation of Gardnerella vaginalis in vitro.Results: RC-101 potently inhibits the cytolytic activity of vaginolysin, the Gardnerella vaginalis toxin, on both erythrocytes and nucleated cells. RC-101 lacks inhibitory activity against planktonic G. vaginalis but markedly decreases biofilm formation.Conclusions: These dual properties, toxin inhibition and biofilm retardation, justify further exploration of RC-101 as a candidate agent for bacterial vaginosis prevention.Keywords: defensin, vaginolysin, bacterial vaginosis, biofilm IntroductionBacterial vaginosis (BV) is a highly prevalent vaginal dysbiosis that has been linked to adverse pregnancy outcomes and enhanced transmission of sexually transmitted infections (STIs). The precise pathogenesis of BV remains unclear. However, loss of vaginal Lactobacillus and overgrowth of Gardnerella vaginalis are thought to be key elements of the disease process. G. vaginalis forms biofilms at the vaginal mucosal surface in vivo, and these appear to contribute to persistence and the frequent failure of antimicrobial therapy for BV.1,2 G. vaginalis biofilms may also be found in male partners of women with BV and may represent a transmissible state for this organism.3 In addition, G. vaginalis produces vaginolysin (VLY), a human-specific cholesterol-dependent cytolysin that lyses epithelial cells and erythrocytes and is thought to play an important role in BV pathogenesis. 4 VLY is inactive at normal vaginal pH (,4.5) but fully active at the higher pH levels noted in the BV milieu. 5Defensins are antimicrobial peptides that have important roles in immune defence and in shaping microbial ecology at mucosal surfaces.6 Q-Defensins, also known as retrocyclins, are 18-residue circular peptides related to the a-and b-defensins. Retrocyclins have broad antibacterial and antiviral activity, but the human retrocyclin gene does not produce a functional product owing to a premature stop codon.7 Based on several studies showing that retrocyclins prevent HIV and herpes simplex virus (HSV) infection, efforts are now under way to develop a topical intravaginal preparation of synthetic retrocyclin RC-101 for STI prophylaxis.8 RC-101 has been shown to lack significant effects on lactobacilli that normally colonize the vaginal tract and to be non-toxic to human cells. We hypothesized that RC-101 might have antibacterial and antitoxin effects against G. vaginalis and VLY that could make it useful for BV prophylaxis. Materials and methods Bacterial strains and growth conditionsGardnerella vaginalis strain 49145 was purchased from ATCC and was grown on solid human blood-bilayer Tween agar (BD Bios...