Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation (IL-17A, CCL20, CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK- and T- lymphocytes, suggesting extravasation to affected tissues. Finally, we profiled the auto-antigen reactivity of MIS-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti-IL6R antibody and/or IVIG, which led to rapid disease resolution.
Objective To assess clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2associated multisystem inflammatory syndrome in children (MIS-C). Study design Children with MIS-C admitted to pediatric intensive care units in New York City between April 23 and May 23, 2020, were included. Demographic and clinical data were collected. Results Of 33 children with MIS-C, the median age was 10 years; 61% were male; 45% were Hispanic/Latino; and 39% were black. Comorbidities were present in 45%. Fever (93%) and vomiting (69%) were the most common presenting symptoms. Depressed left ventricular ejection fraction was found in 63% of patients with median ejection fraction of 46.6% (IQR, 39.5-52.8). C-reactive protein, procalcitonin, d-dimer, and pro-B-type natriuretic peptide levels were elevated in all patients. For treatment, intravenous immunoglobulin was used in 18 (54%), corticosteroids in 17 (51%), tocilizumab in 12 (36%), remdesivir in 7 (21%), vasopressors in 17 (51%), mechanical ventilation in 5 (15%), extracorporeal membrane oxygenation in 1 (3%), and intra-aortic balloon pump in 1 (3%). The left ventricular ejection fraction normalized in 95% of those with a depressed ejection fraction. All patients were discharged home with median duration of pediatric intensive care unit stay of 4.7 days (IQR, 4-8 days) and a hospital stay of 7.8 days (IQR, 6.0-10.1 days). One patient (3%) died after withdrawal of care secondary to stroke while on extracorporeal membrane oxygenation. Conclusions Critically ill children with coronavirus disease-2019-associated MIS-C have a spectrum of severity broader than described previously but still require careful supportive intensive care. Rapid, complete clinical and myocardial recovery was almost universal.
In children who suffer out of hospital cardiac arrest, targeted hypothermia at 33.0 C confers no benefit when compared to targeted normothermia at 36.8 C. Level of evidence: 2B (RCT with wide CIs)Appraised by: Andrew Claxton Citation: Moler FW, Silverstein FS, Holubkov R and the THAPCA Trial Investigators. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Eng
BACKGROUND-Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after inhospital cardiac arrest are limited.
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