Multisystem inflammatory syndrome in children: Salient echocardiogram findings in the acute phase and longitudinal follow-up

Background Coronary artery (CA) abnormalities and left ventricular (LV) systolic dysfunction have been reported in multisystem inflammatory syndrome in children (MIS-C);however, a thorough review of all findings on transthoracic echocardiogram (TTE) with long term follow-up is lacking. Objectives Comprehensively describe the findings on TTE during the acute phase of MIS-C and how those findings change on serial follow-up 6 months after diagnosis. Methods Pediatric patients meeting CDC criteria for MIS-C were included, with data collected from acute phase (T0), outpatient follow-up at 2 weeks (T1), 6–8 weeks (T2), and 6 months (T3), including TTE findings of descending aorta Doppler profile, CA abnormalities, valvar regurgitation, LV systolic function and pericardial effusion. Results Fifty patients (52% male) were included;45 (90%) were SARS-CoV-2 IgG antibody positive, 13 (26%) PCR positive, and 8 (16%) positive for both. Mean age was 8.3 years (range 9 months - 17 years). Holodiastolic flow reversal in descending aorta was seen in 72% at T0, in 6% at T1, with complete resolution in all by T2. CA abnormalities were seen in 52% at T0, 31% at T1, 13% at T2 and none at T3. Mitral regurgitation was present in 84% at T0, 40% at T1, 36% at T2, and 24% by T3. LV systolic dysfunction (ejection fraction <55%) occurred in 52% at T0, with resolution by discharge in 69%, and complete resolution by T2. Trivial to small pericardial effusion was present in 48% at T0, 13% at T1, 3% at T2 and 4% by T3. Conclusion In addition to CA abnormalities and LV systolic dysfunction, holodiastolic flow reversal in the descending aorta, valvar regurgitation and pericardial effusion are prominent findings in MIS-C. Longitudinal follow-up shows improvement in all.

Six Month Follow-up of Patients With Multi-System Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: Myocardial dysfunction and coronary abnormalities are prominent features of multisystem inflammatory syndrome in children (MIS-C). In this study we aim to evaluate the early and midterm outcomes of MIS-C. METHODS: This is a longitudinal 6-month cohort study of all children admitted and treated for MIS-C from April 17 to June 20, 2020. Patients were followed ∼2 weeks, 8 weeks, and 6 months postadmission, with those with coronary aneurysms evaluated more frequently. RESULTS: Acutely, 31 (62%) patients required intensive care with vasoactive support, 26 (52%) had left ventricular (LV) systolic dysfunction, 16 (32%) had LV diastolic dysfunction, 8 (16%) had coronary aneurysms (z score ≥2.5), and 4 (8%) had coronary dilation (z score <2.5). A total of 48 patients (96%) received immunomodulatory treatment. At 2 weeks, there was persistent mild LV systolic dysfunction in 1 patient, coronary aneurysms in 2, and dilated coronary artery in 1. By 8 weeks through 6 months, all patients returned to functional baseline with normal LV systolic function and resolution of coronary abnormalities. Cardiac MRI performed during recovery in select patients revealed no myocardial edema or fibrosis. Some patients demonstrated persistent diastolic dysfunction at 2 weeks (5, 11%), 8 weeks (4, 9%), and 6 months (1, 4%). CONCLUSIONS: Children with MIS-C treated with immunomodulators have favorable early outcomes with no mortality, normalization of LV systolic function, recovery of coronary abnormalities, and no inflammation or scarring on cardiac MRI. Persistence of diastolic dysfunction is of uncertain significance and indicates need for larger studies to improve understanding of MIS-C. These findings may help guide clinical management, outpatient monitoring, and considerations for sports clearance.

Features of Intestinal Disease Associated With COVID-Related Multisystem Inflammatory Syndrome in Children.

ABSTRACT: Multisystem inflammatory syndrome in children (MIS-C) is a recently identified syndrome that appears to be temporally associated with novel coronavirus 2019 infection. MIS-C presents with fever and evidence of systemic inflammation, which can manifest as cardiovascular, pulmonary, neurologic, and gastrointestinal (GI) system dysfunction. Presenting GI symptoms are seen in the majority, including abdominal pain, diarrhea, and vomiting. Any segment of the GI tract may be affected; however, inflammation in the ileum and colon predominates. Progressive bowel wall thickening can lead to luminal narrowing and obstruction. Most will have resolution of intestinal inflammation with medical therapies; however, in rare instances, surgical resection may be required.

Characteristics and risk factors associated with critical illness in pediatric COVID-19.

BACKGROUND: While much has been reported regarding the clinical course of COVID-19 in children, little is known regarding factors associated with organ dysfunction in pediatric COVID-19. We describe critical illness in pediatric patients with active COVID-19 and identify factors associated with PICU admission and organ dysfunction. This is a retrospective chart review of 77 pediatric patients age 1 day to 21 years admitted to two New York City pediatric hospitals within the Northwell Health system between February 1 and April 24, 2020 with PCR + SARS-CoV-2. Descriptive statistics were used to describe the hospital course and laboratory results and bivariate comparisons were performed on variables to determine differences. RESULTS: Forty-seven patients (61%) were admitted to the general pediatric floor and thirty (39%) to the PICU. The majority (97%, n = 75) survived to discharge, 1.3% (n = 1) remain admitted, and 1.3% (n = 1) died. Common indications for PICU admission included hypoxia (50%), hemodynamic instability (20%), diabetic ketoacidosis (6.7%), mediastinal mass (6.7%), apnea (6.7%), acute chest syndrome in sickle cell disease (6.7%), and cardiac dysfunction (6.7%). Of PICU patients, 46.7% experienced any significant organ dysfunction (pSOFA > = 2) during admission. Patients aged 12 years or greater were more likely to be admitted to a PICU compared to younger patients (p = 0.015). Presence of an underlying comorbidity was not associated with need for PICU admission (p = 0.227) or organ dysfunction (p = 0.87). Initial white blood cell count (WBC), platelet count, and ferritin were not associated with need for PICU admission. Initial C-reactive protein was associated with both need for PICU admission (p = 0.005) and presence of organ dysfunction (p = 0.001). Initial WBC and presenting thrombocytopenia were associated with organ dysfunction (p = 0.034 and p = 0.003, respectively). CONCLUSIONS: Age over 12 years and initial CRP were associated with need for PICU admission in COVID-19. Organ dysfunction was associated with elevated admission CRP, elevated WBC, and thrombocytopenia. These factors may be useful in determining risk for critical illness and organ dysfunction in pediatric COVID-19.

Characteristics, Cardiac Involvement, and Outcomes of Multisystem Inflammatory Syndrome of Childhood Associated with severe acute respiratory syndrome coronavirus 2 Infection.

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection. Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.

Early Experience of COVID-19 in a US Children's Hospital.

OBJECTIVES: We aim to describe the demographics, clinical presentation, hospital course, and severity of pediatric inpatients with coronavirus disease 2019 (COVID-19), with an emphasis on healthy, immunocompromised, and chronically ill children. METHODS: We conducted a single-center retrospective cohort study of hospitalized children aged younger than 22 years with COVID-19 infection at Steven and Alexandra Cohen Children's Medical Center at Northwell Health. Cases were identified from patients with fever and/or respiratory symptoms who underwent a nucleic acid amplification-based test for severe acute respiratory syndrome coronavirus 2. RESULTS: Sixty-five patients were identified. The median age was 10.3 years (interquartile range, 1.4 months to 16.3 years), with 48% of patients older than 12 years and 29% of patients younger than 60 days of age. Fever was present in 86% of patients, lower respiratory symptoms or signs in 60%, and gastrointestinal symptoms in 62%. Thirty-five percent of patients required ICU care. The white blood cell count was elevated in severe disease (P = .0027), as was the C-reactive protein level (P = .0192), compared with mild and moderate disease. Respiratory support was required in 34% of patients. Severity was lowest in infants younger than 60 days of age and highest in chronically ill children; 79% of immunocompromised children had mild disease. One death was reported. CONCLUSIONS: Among children who are hospitalized for COVID-19, most are younger than 60 days or older than 12 years of age. Children may have severe infection requiring intensive care support. The clinical course of immunocompromised patients was not more severe than that of other children. Elevated white blood cell count and C-reactive protein level are associated with greater illness severity.

Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR-positive SARS-CoV-2 infection, including drug-induced changes in the corrected QT interval.

BACKGROUND: There is limited data regarding the electrophysiological abnormalities and arrhythmias in children with COVID-19, including those associated with treatment using potentially proarrhythmic hydroxychloroquine (HCQ) and azithromycin (AZN). OBJECTIVES: To describe the electrophysiologic findings and arrhythmias associated with pediatric COVID-19 and its treatment. METHODS: A single-center retrospective chart review was undertaken and included all patients with (1) symptoms of COVID-19 and (2) PCR-positive nasopharyngeal swabs for SARS-CoV-2 who were placed on continuous telemetry for the duration of their hospitalization during March through May, 2020. RESULTS: Thirty-six patients were included in the study. Significant arrhythmias were found in 6 (nonsustained ventricular tachycardia in 5 and sustained atrial tachycardia in 1). All were self-resolving and half prompted prophylactic antiarrhythmic therapy. Patients with significant arrhythmias were likely to have noncardiac comorbidities (4/6), but these were not more common than in patients without arrhythmias (20/30, P = 1). The use of HCQ was associated with statistically significant QTc prolongation (413 ± 19 ms vs 425 ± 16 ms, P =.005). QTc was not statistically different in patients with and without arrhythmias (425 ± 15 ms vs 425 ± 15 ms, P = 1). CONCLUSIONS: In pediatric patients with PCR-positive active COVID-19 infection, significant arrhythmias are infrequent, but are more common than expected in a general pediatric population. Comorbidities are not more common in patients with arrhythmias than in patients without arrhythmias. COVID-19 treatment using HCQ is associated with QTc prolongation but was not associated with arrhythmias in pediatric patients.