Heterogeneity in the evaluation of suspected MIS-C: a cross-sectional vignette-based survey.

BACKGROUND AND OBJECTIVES: Multisystem Inflammatory Syndrome in Children (MIS-C) is an emerging complication of COVID-19 which lacks a definitive diagnostic test and evidence-based guidelines for workup. We sought to assess practitioners' preferences when initiating a workup for pediatric patients presenting with symptoms concerning for MIS-C. METHODS: In a cross-sectional vignette-based survey, providers were presented with clinical vignettes of a patient presenting with 24 h of fever from a community with high rates of COVID-19. Respondents were asked about their general practices in pursuing a workup for potential MIS-C including testing obtained, criteria for diagnosis, and timing to confirm or rule out the diagnosis. RESULTS: Most of the 174 respondents were physicians from the United States at academic medical centers. The majority of providers would not initiate MIS-C workup for fever and non-specific symptoms unless the fever lasted more than 72 h. Skin rash, abdominal pain, and shortness of breath were symptoms that raised greatest concern for MIS-C. Most providers would obtain COVID-19 PCR or antigen testing, plus blood work, in the initial workup. The list of laboratory studies providers would obtain is extensive. Providers primarily rely on cardiac involvement to confirm a MIS-C diagnosis, and establishing a diagnosis takes 24-48 h. CONCLUSIONS: Significant heterogeneity exists amongst providers as to when to initiate the MIS-C workup, the order and content of the workup, and how to definitively diagnose MIS-C. A diagnostic test with high sensitivity and specificity for MIS-C and refined evidence-based guidelines are needed to expedite diagnosis and treatment.

Monocyte anisocytosis increases during multisystem inflammatory syndrome in children with cardiovascular complications.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A complex, time-consuming laboratory evaluation is currently required to distinguish MIS-C from other illnesses. New assays are urgently needed early in the evaluation process to expedite MIS-C workup and initiate treatment when appropriate. This study aimed to measure the performance of a monocyte anisocytosis index, obtained on routine complete blood count (CBC), to rapidly identify subjects with MIS-C at risk for cardiac complications. METHODS: We measured monocyte anisocytosis, quantified by monocyte distribution width (MDW), in blood samples collected from children who sought medical care in a single medical center from April 2020 to October 2020 (discovery cohort). After identifying an effective MDW threshold associated with MIS-C, we tested the utility of MDW as a tier 1 assay for MIS-C at multiple institutions from October 2020 to October 2021 (validation cohort). The main outcome was the early screening of MIS-C, with a focus on children with MIS-C who displayed cardiac complications. The screening accuracy of MDW was compared to tier 1 routine laboratory tests recommended for evaluating a child for MIS-C. RESULTS: We enrolled 765 children and collected 846 blood samples for analysis. In the discovery cohort, monocyte anisocytosis, quantified as an MDW threshold of 24.0, had 100% sensitivity (95% CI 78-100%) and 80% specificity (95% CI 69-88%) for identifying MIS-C. In the validation cohort, an initial MDW greater than 24.0 maintained a 100% sensitivity (95% CI 80-100%) and monocyte anisocytosis displayed a diagnostic accuracy greater that other clinically available hematologic parameters. Monocyte anisocytosis decreased with disease resolution to values equivalent to those of healthy controls. CONCLUSIONS: Monocyte anisocytosis detected by CBC early in the clinical workup improves the identification of children with MIS-C with cardiac complications, thereby creating opportunities for improving current practice guidelines.

Temporal Variability of Microparticles Under the Seattle Aquarium, Washington State: Documenting the Global Covid-19 Pandemic.

Anthropogenic debris including microparticles (<5 mm) are ubiquitous in marine environments. The Salish Sea experiences seasonal fluctuations in precipitation, river discharge, sewage overflow events, and tourism-all variables previously thought to have an impact on microparticle transport and concentrations. Our goals are two-fold: 1) describe long-term microparticle contamination data including concentration, type, and size; and 2) determine if seasonal microparticle concentrations are dependent on environmental or tourism variables in Elliott Bay, Salish Sea. We sampled 100 L of seawater at a depth of approximately 9 m at the Seattle Aquarium, Seattle, Washington State, United States, approximately every two weeks from 2019 through 2020 and used an oil extraction protocol to separate microparticles. We found that microparticle concentrations ranged from 0 to 0.64 particles L-1 and fibers were the most common type observed. Microparticle concentrations exhibited a breakpoint on 10 April 2020, where estimated slope and associated microparticle concentration significantly declined. Further, when considering both environmental as well as tourism variables, temporal microparticle concentration was best described by a mixed-effects model, with tourism as the fixed effect and the person counting microparticles as the random effect. Although monitoring efforts presented set out to identify effects of seasonality and interannual differences in microparticle concentrations, it instead captured an effect of decreased tourism due to the global Covid-19 pandemic. Long-term monitoring is critical to establish temporal microparticle concentrations and to help researchers understand if there are certain events, both seasonal and sporadic (e.g., rain events, tourism, or global pandemics), when the marine environment is more at risk from anthropogenic pollution. Environ Toxicol Chem 2022;41:917-930. © 2021 Seattle Aquarium. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.