26-CCC-14971-ACC MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN (MIS-C): HOW EARLY IDENTIFICATION CAN PREVENT PROGRESSION OF CARDIOVASCULAR SYSTEM HYPERINFLAMMATION AND DEATH IN CHILDREN AND ADOLESCENTS

Multisystem inflammatory syndrome in children associated with SARS-CoV-2 in a solid organ transplant recipient.

Multisystem Inflammatory Syndrome in Children and Kawasaki Disease: Two Different Illnesses with Overlapping Clinical Features

To compare clinical characteristics and outcomes of children admitted to the PICU for severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children. The secondary objective was to identify explanatory factors associated with outcome of critical illness defined by a composite index of in-hospital mortality and organ system support requirement. Retrospective cohort study. Thirty-eight PICUs within the Viral Infection and Respiratory Illness Universal Study registry from March 2020 to January 2021. Children less than 18 years with severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children. Of 394 patients, 171 (43.4%) had multisystem inflammatory syndrome in children. Children with multisystem inflammatory syndrome in children were more likely younger (2-12 yr vs adolescents; p < 0.01), Black (35.6% vs 21.9%; p < 0.01), present with fever/abdominal pain than cough/dyspnea (p < 0.01), and less likely to have comorbidities (33.3% vs 61.9%; p < 0.01) compared with those without multisystem inflammatory syndrome in children. Inflammatory marker levels, use of inotropes/vasopressors, corticosteroids, and anticoagulants were higher in multisystem inflammatory syndrome in children patients (p < 0.01). Overall mortality was 3.8% (15/394), with no difference in the two groups. Diagnosis of multisystem inflammatory syndrome in children was associated with longer duration of hospitalization as compared to nonmultisystem inflammatory syndrome in children (7.5 d[interquartile range, 5-11] vs 5.3 d [interquartile range, 3-11 d]; p < 0.01). Critical illness occurred in 164 patients (41.6%) and was more common in patients with multisystem inflammatory syndrome in children compared with those without (55.6% vs 30.9%; p < 0.01). Multivariable analysis failed to show an association between critical illness and age, race, sex, greater than or equal to three signs and symptoms, or greater than or equal to two comorbidities among the multisystem inflammatory syndrome in children cohort. Among nonmultisystem inflammatory syndrome in children patients, the presence of greater than or equal to two comorbidities was associated with greater odds of critical illness (odds ratio 2.95 [95% CI, 1.61-5.40]; p < 0.01). This study delineates significant clinically relevant differences in presentation, explanatory factors, and outcomes among children admitted to PICU with severe acute respiratory syndrome coronavirus 2-related illness stratified by multisystem inflammatory syndrome in children.

IL-1 receptor antagonist, MIS-C, and the peculiar autoimmunity of SARS-CoV-2

COVID-19 herd immunity by immunisation: are children in the herd?

Racial and Socioeconomic Disparities in Multisystem Inflammatory Syndrome in Children in the United States

Background Although multisystem inflammatory syndrome in children (MIS-C) incidence has decreased, cases continue to occur and can have notable morbidity and mortality. This investigation evaluates clinical and demographic risk factors for death from MIS-C.Table 1.Demographic and clinical risk factors for death in children with Multisystem Inflammatory Syndrome in Children, United States, 2020-2022 Methods We evaluated children reported to CDC national MIS-C surveillance with illness onset February 2020–December 2022 and known illness outcome. We performed multivariable logistic regression to estimate odds of death compared with survival for patient characteristics and MIS-C organ involvement. Model covariates were selected a priori including age at MIS-C onset, date of MIS-C onset, race and ethnicity, and presence of any underlying medical condition. To compare risk of death across the pandemic we evaluated patients with date of MIS-C onset in five pandemic waves corresponding to peaks of MIS-C activity.Table 2.Organ system involvement risk factors for death in children with Multisystem Inflammatory Syndrome in Children, United States, 2020-2022 Results Of 8,767 MIS-C cases reported, there were 76 (9%) deaths (Table 1). Compared with children aged 5–11 years, children &amp;lt; 1 year and 16–20 years had increased odds of death (aOR 4.8 [1.7–13.6], p&amp;lt; 0.01, and 8.2 [4.6–14.8], p&amp;lt; 0.001, respectively). American Indian/alaska Native (AIAN) and Native Hawaiian/Pacific Islander (NHPI) children had increased odds of death compared with White non-Hispanic children (aOR 5.4 [1.4–20.9, p=0.01 and 5.9 [1.5–23.1, p=0.01, respectively). Children with MIS-C illness onset after wave 1 had decreased odds of death compared with those during wave 1. Presence of &amp;gt;1 underlying medical condition was associated with higher odds of death (aOR 2.3 [1.5–3.7, p&amp;lt; 0.001); diabetes, congenital heart disease, neurologic, immunosuppressive/autoimmune, and noncardiac congenital disorders were all independently associated with death. Cardiovascular, respiratory, neurologic, and renal MIS-C organ involvement increased odds of death while children with mucocutaneous involvement had decreased odds (Table 2). Conclusion Younger (&amp;lt; 1 year) and older (16-20 years) age, AIAN and NHPI race and ethnicity, MIS-C early in the pandemic, and underlying medical conditions are risk factors for death from MIS-C. Cardiovascular, respiratory, neurologic, and renal involvement increased risk of death. Identifying risk factors associated with death may help clinicians with management and prognosis. Disclosures Regina Simeone, PhD, Pfizer: Stocks/Bonds (Private Company)

Multisystem Inflammatory Syndrome in

While most children with multisystem inflammatory syndrome in children have rapid recovery of cardiac dysfunction, little is known about the long-term outcomes regarding exercise capacity. We aimed to compare the exercise capacity among patients with multisystem inflammatory syndrome in children versus viral/idiopathic myocarditis at 3-6 months after initial diagnosis. We performed a retrospective cohort study among patients with multisystem inflammatory syndrome in children in June 2020 to May 2021 and patients with viral/idiopathic myocarditis in August 2014 to January 2020. Data from cardiopulmonary exercise test as well as echocardiographic and laboratory data were obtained. Inclusion criteria included diagnosis of multisystem inflammatory syndrome in children or viral/idiopathic myocarditis, exercise test performed within 3-6 months of hospital discharge, and maximal effort on cardiopulmonary exercise test as determined by respiratory exchange ratio >1.10. Thirty-one patients with multisystem inflammatory syndrome in children and 25 with viral/idiopathic myocarditis were included. The mean percent predicted peak VO2 was 90.84% for multisystem inflammatory syndrome in children patients and 91.08% for those with viral/idiopathic myocarditis (p-value 0.955). There were no statistically significant differences between the groups with regard to percent predicted maximal heart rate, metabolic equivalents, percent predicted peak VO2, percent predicted anerobic threshold, or percent predicted O2 pulse. There was a statistically significant correlation between lowest ejection fraction during hospitalisation and peak VO2 among viral/idiopathic myocarditis patients (r: 0.62, p-value 0.01) but not multisystem inflammatory syndrome in children patients (r: 0.1, p-value 0.6). Patients with multisystem inflammatory syndrome in children and viral myocarditis appear to, on average, have normal exercise capacity around 3-6 months following hospital discharge. For patients with viral/idiopathic myocarditis, those with worse ejection fraction during hospitalisation had lower peak VO2 on cardiopulmonary exercise test.

Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases. To elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations). Children with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84-100% and specificity 80-100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical diseases with high sensitivity and specificity. Among MIS-C children, elevated levels of MMPs were seen in children requiring intensive care unit admission as compared to children not needing intensive care. Similar findings were noted when children with severe/moderate COVID-19 were compared to children with mild COVID-19. Finally, MMP levels exhibited significant correlation with laboratory parameters, including lymphocyte counts, CRP, D-dimer, Ferritin and Sodium levels. Our findings suggest that MMPs play a pivotal role in the pathogenesis of MIS-C and COVID-19 in children and may help distinguish MIS-C from other conditions with overlapping clinical presentation.

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. 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. 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. 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.

KAWASAKI DISEASE, MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN AND COVID-19 IN A TERTIARY PEDIATRIC HOSPITAL IN MONTRÉAL, CANADA

Weight excess association with severity in children and adolescents with COVID-19: A systematic review.

It is known established that the cardiac effects of COVID-19 infection are associated with poor prognosis and high mortality rates in infected patients. The aim of this study was to evaluate the cardiac effects of COVID-19 infection in paediatric patients and identify the correlations between clinical and laboratory data and the degree of cardiac involvement. A retrospective data analysis was conducted on 64 paediatric patients at Gazi University Department of Pediatrics who were treated as inpatients with a diagnosis of COVID-19. Patients were classified as "COVID-19-related cardiac involvement cases" if their electrocardiogram and echocardiogram results indicated a pathology and/or if their laboratory data indicated increased cardiac enzymes. All patients were divided into subgroups based on whether they had cardiac involvement and whether they were diagnosed with multisystem inflammatory syndrome in children. In comparison to patients who did not have cardiac involvement, those with cardiac involvement had significantly higher levels of hs-Troponin T, Pro-BNP, and D-dimer. Patients with multisystem inflammatory syndrome in children had significantly longer PR intervals than those without multisystem inflammatory syndrome in children (p = 0.0001). Patients with multisystem inflammatory syndrome in children had a significantly higher rate of pathological valve insufficiencies (68.1%) than those without multisystem inflammatory syndrome in children (14.2%) (p = 0.001). In our study, the strongest predictive biomarker of cardiac involvement in paediatric patients with COVID-19 infection was determined to be hs-Troponin T. It was observed that pathologic electrocardiogram changes could reflect cardiac involvement in the absence of any other signs. Patients with multisystem inflammatory syndrome in children exhibited significantly greater rates of pathologic echocardiogram findings and myocardial dysfunction than those without multisystem inflammatory syndrome in children. In all patients, pathologic electrocardiogram and echocardiogram findings were found to be strongly associated with the severity of inflammation.

The researchers identified cases of multisystem inflammatory syndrome in children, which was linked to COVID-19 starting in 2020. Multisystem inflammatory syndrome in children is associated with significant cardiovascular morbidity in the acute phase. A small number of articles in the literature have recorded the long-term myocardial effects of multisystem inflammatory syndrome in children treated in pediatric intensive care units. Our study aimed to investigate the late cardiac outcomes of multisystem inflammatory syndrome in children using cardiac magnetic resonance imaging.A median of 16 months had passed after the onset of the disease in multisystem inflammatory syndrome in children. Ejection fraction (%), cardiac output (L/min), stroke volume (mL), end-diastolic volume index (mL/m2), cardiac index (L/min/m2), and stroke volume index (mL/m2) were all significantly lower in multisystem inflammatory syndrome in children. During at least a 1-year follow-up, minor cardiac damage was discovered in 26% of individuals who underwent cardiac magnetic resonance imaging. In addition, none of the 23 infants showed symptoms of late gadolinium enhancement or pericardial effusion. While all patients underwent cardiac magnetic resonance imaging, the transthoracic echocardiogram evaluation revealed normal heart function.Our study found no evidence of late gadolinium enhancement, which indicates cardiac fibrosis in cardiac magnetic resonance imaging performed after a prolonged hospitalization in multisystem inflammatory syndrome in children who were admitted to the intensive care unit. This absence of late gadolinium enhancement is a reassuring finding, suggesting that the long-term cardiac outcomes of multisystem inflammatory syndrome in children may not be as severe as initially feared. However, the long-term cardiac magnetic resonance imaging results revealed mild left ventricular dysfunction in these patients that could not be detected via a transthoracic echocardiogram.