Multisystem Inflammatory Syndrome in Children Associated With Coronavirus Disease 2019 in a Children's Hospital in New York City: Patient Characteristics and an Institutional Protocol for Evaluation, Management, and Follow-Up.

OBJECTIVES: The disease caused by severe acute respiratory syndrome coronavirus 2, known as coronavirus disease 2019, has resulted in a global pandemic. Reports are emerging of a new severe hyperinflammatory syndrome related to coronavirus disease 2019 in children and adolescents. The Centers for Disease Control and Prevention has designated this disease multisystem inflammatory syndrome in children. Our objective was to develop a clinical inpatient protocol for the evaluation, management, and follow-up of patients with this syndrome. DATA SOURCES: The protocol was developed by a multidisciplinary team based on relevant literature related to coronavirus disease 2019, multisystem inflammatory syndrome in children, and related inflammatory syndromes, as well as our experience caring for children with multisystem inflammatory syndrome in children. Data were obtained on patients with multisystem inflammatory syndrome in children at our institution from the pre-protocol and post-protocol periods. DATA SYNTHESIS: Our protocol was developed in order to identify cases of multisystem inflammatory syndrome in children with high sensitivity, stratify risk to guide treatment, recognize co-infectious or co-inflammatory processes, mitigate coronary artery abnormalities, and manage hyperinflammatory shock. Key elements of evaluation include case identification using broad clinical characteristics and comprehensive laboratory and imaging investigations. Treatment centers around glucocorticoids and IV immunoglobulin with biologic immunomodulators as adjuncts. Multidisciplinary follow-up after discharge is indicated to manage continued outpatient therapy and evaluate for disease sequelae. In nearly 2 months, we admitted 54 patients with multisystem inflammatory syndrome in children, all of whom survived without the need for invasive ventilatory or mechanical circulatory support. After institution of this protocol, patients received earlier treatment and had shorter lengths of hospital stay. CONCLUSIONS: This report provides guidance to clinicians on evaluation, management, and follow-up of patients with a novel hyperinflammatory syndrome related to coronavirus disease 2019 known as multisystem inflammatory syndrome in children. It is based on the relevant literature and our experience. Instituting such a protocol during a global pandemic is feasible and is associated with patients receiving treatment and returning home more quickly.

Preclinical Antimalarial Combination Study of M5717, a Plasmodium falciparum Elongation Factor 2 Inhibitor, and Pyronaridine, a Hemozoin Formation Inhibitor.

Antimalarial drug resistance in the Plasmodium falciparum parasite poses a constant challenge for drug development. To mitigate this risk, new antimalarial medicines should be developed as fixed-dose combinations. Assessing the pharmacodynamic interactions of potential antimalarial drug combination partners during early phases of development is essential in developing the targeted parasitological and clinical profile of the final drug product. Here, we have studied the combination of M5717, a P. falciparum translation elongation factor 2 inhibitor, and pyronaridine, an inhibitor of hemozoin formation. Our test cascade consisted of in vitro isobolograms as well as in vivo studies in the P. falciparum severe combined immunodeficient (SCID) mouse model. We also analyzed pharmacokinetic and pharmacodynamic parameters, including genomic sequencing of recrudescent parasites. We observed no pharmacokinetic interactions with the combination of M5717 and pyronaridine. M5717 did not negatively impact the rate of kill of the faster-acting pyronaridine, and the latter was able to suppress the selection of M5717-resistant mutants, as well as significantly delay the recrudescence of parasites both with suboptimal and optimal dosing regimens.

Early Treatment of Multisystem Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory illness occurring after severe acute respiratory syndrome coronavirus 2 infection. The optimal treatment of MIS-C is unknown, although prior studies have indicated benefits of intravenous immunoglobulin (IVIG) and glucocorticoids. We hypothesize that early treatment with glucocorticoids is associated with shorter hospital length of stay (LOS). METHODS: This study is a multicenter retrospective cohort study of patients hospitalized with MIS-C over a roughly 1-year period. The primary outcome was hospital LOS comparing subjects who received glucocorticoids within 48 hours of arrival to the treating hospital to those who did not. Secondary outcomes included ICU LOS. Unadjusted and adjusted analyses were performed. RESULTS: The final analysis included 131 subjects. Subjects who received early glucocorticoids were more likely to receive early IVIG and to require ICU admission. Early glucocorticoid administration was associated with shorter ICU LOS (4 vs 9 days, P = .004) in the unadjusted analysis. In the adjusted analysis, early glucocorticoid administration and early IVIG administration were both independently associated with shorter hospital LOS (incidence rate ratio 0.75, P = .025; incidence rate ratio 0.56, P = .026, respectively). CONCLUSIONS: Glucocorticoids and intravenous immunoglobulin were independently associated with shorter hospital length of stay when given early in hospitalization to MIS-C patients after accounting for potential confounding factors. The optimal dose and duration of treatment require further investigation, but this study supports early combination therapy with both IVIG and glucocorticoids for all children hospitalized with MIS-C.