Presence of coronary aneurysms during Kawasaki Disease (KD) correlates with lower levels of autoantibodies to both full form and spliced variant of immune regulator Del-1.

Kawasaki disease (KD), a rare multisystem inflammatory condition that predominantly affects children under six years of age, is the leading cause of childhood-acquired heart disease in developed countries. The pathogenesis is unknown, but studies support that an infectious stimulus triggers an autoimmune reaction in a genetically susceptible child. Recent studies demonstrated an association with autoantibody response to Del-1 (also known as EDIL3) in children with KD. Del-1 is an extracellular matrix protein that is expressed both in macrophages and vascular endothelium. Del-1 has an anti-inflammatory role by preventing leucocyte migration to inflammatory sites. Del-1 has two expression variants and genetic variants of Del-1 have been associated with the risk of intracranial aneurysms. Due to the physiologic plausibility for a role during KD, we chose to assess if autoantibodies against DEL-1 are seen in a larger cohort of children with KD and to assess if responses correlated to aneurysm formation. Contrary to prior findings, in comparison to febrile controls, autoantibodies were not overall higher in children with KD. Elevation in Post-IVIG samples in comparison to pre-IVIG and convalescent samples supports the commonality of anti-Del-1 antibodies. Autoantibodies were notably lower in children with KD who had coronary Z score elevations in comparison to those who did not.

A hospital based comparative study of the first and second waves of Covid-19 related multi-system inflammatory syndrome in children

Introduction: Studies have shown the differential impact of the second surge of acute Covid-19 infection, across age, clinical outcome and ethnicity. How these factors impact the clinical characteristics and outcome of multisystem inflammatory syndrome in children (MIS-C) is largely unknown. Objectives: This hospital based comparative study was undertaken to analyse the clinical characteristics and outcomes of patients admitted with MIS-C during the two waves of Covid-19 infection in a tertiary care teaching hospital in South India. Method: Patients admitted between September 2020 and October 2021 with MIS-C were included in this study. Patient demographics, laboratory values and treatment details were compared between the two surges of COVID 19 related MIS-C. Results: Sixty-five children were admitted with MIS-C in the first wave and 73 in the second wave. More children were referred with a diagnosis of MIS-C in the second wave (p=0.001). There was no significant difference in the mean age or malefemale ratio between the two waves. A significantly higher proportion of children in the second wave had cervical lymphadenitis (p=0.02). Need for intensive care unit (ICU) admission (p<0.001), shock (p<0.001), respiratory support (p<0.001) and multiorgan involvement (p<0.001) were significantly lower in the second wave.Conclusions: A significantly higher proportion of children with MIS-C in the second wave of Covid-19 infection had cervical lymphadenitis. The need for ICU admission, shock, respiratory support and multi-organ involvement were significantly lower in children with MIS-C in the second wave of Covid-19 infection © Open Access Article published under the Creative Commons Attribution CC-BY License

Giant Coronary Aneurysm in an Infant with Multisystem Inflammatory Syndrome.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2), also known as COVID-19, has rapidly spread resulting in a worldwide pandemic. Although COVID-19 infections in children are generally mild and nonfatal, there is increasing recognition of its association with the multisystem inflammatory syndrome in children (MIS-C), leading to serious illness and possible long-term complications. This report describes a 6-month-old Indian infant who presented with a 4-day history of fever with nonspecific signs of viral illness and erythematous rash. Although the initial echocardiogram was normal, subsequent scans showed progressive dilatation of bilateral coronary arteries. Despite the timely intervention, he developed left coronary artery thrombosis, leading to myocardial infarction. His SARS-CoV-2 antibody titers were strongly positive. Through this case, we discuss the management of MIS-C with coronary artery involvement. The long-term outcome of coronary artery aneurysm due to MIS-C remains unknown and close follow-up is important. Further research is pivotal for a better understanding of MIS-C.

Appendicitis as a Leading Manifestation of Kawasaki Disease in Older Children.

Kawasaki disease (KD) is a systematic inflammatory disease with multiple organ involvement. Timely diagnosis and prompt management are essential for successful treatment. KD, with an atypical presentation, remains a diagnostic challenge for physicians. We report a five-year-old boy who presented with appendicitis. An appendectomy was performed; however, his fever persisted. The boy was diagnosed with KD and intravenous immunoglobulin was administered. His symptoms resolved, and he had an uneventful recovery. Furthermore, we performed a literature review with 13 cases identified in the literature. Most cases were male, and the average age was older than typical for KD. In conclusion, KD may present with abdominal complaints and appendicitis may be a rare initial presentation of KD. Multidisciplinary cooperation and high awareness are warranted for timely diagnosis, especially in older children experiencing persistent fever after an appendectomy.

Coronary Artery Changes in Patients with Multisystem Inflammatory Syndrome in Children: Los Angeles Experience.

We compared cardiac findings in patients with multisystem inflammatory syndrome in children and Kawasaki disease in the first 6 months of the 2020 coronavirus disease pandemic to patients with Kawasaki disease during 2016-2019. We saw a high rate of coronary aneurysms in 2020, with a similar rate of coronary involvement but greater volume and incidence of cardiac dysfunction compared with previous years.

Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C).

Endothelial insult and damage is one of the reported consequences of SARS-CoV-2 infection. It has been associated with severe inflammation, thrombotic phenomena and profound hypoxemia in critically ill patients. Endothelial activation leads to a loss of the endothelium's antithrombotic properties which, under normal conditions, are maintained by the endothelial glycocalyx, a carbohydrate-rich layer that covers the luminal surface of endothelial cells. In children, one of the serious forms of SARS-CoV-2 virus disease (COVID-19) is multisystem inflammatory syndrome (MIS-C). This new disease is characterized by a large inflammatory response and frequent cardiovascular, cutaneous and gastrointestinal disorders. We describe the first two cases of critically ill children with MIS-C who evidenced a large inflammatory response associated with elevated plasma and imaging biomarkers of endothelial activation and endothelial glycocalyx degradation. This microcirculation involvement in MIS-C could, at least partially, explain some of the clinical manifestations and laboratory and imaging alterations found in these patients. These findings contribute to a better understanding of this disease and suggest that medications to modulate the inflammatory response and protect or restore the endothelial glycocalyx should be considered in future studies.

Pediatric multisystem SARS COV2 with versus without cardiac involvement: a multicenter study from Latin America.

Latin America (LATAM) children offer special insight into Severe Acute Respiratory Syndrome Coronavirus 2 (SARS COV2) due to high-risk race/ethnicity, variability in medical resources, diverse socioeconomic background, and numerous involved organ systems. This multinational study of LATAM youth examined the distinguishing features of acute or late multisystem SARS COV2 with versus without cardiac involvement. A consecutive sample of youth 0-18 years old (N = 98;50% male) presenting with multisystem SARS COV2 to 32 centers in 10 Latin American countries participating in a pediatric cardiac multi-imaging society were grouped as with versus without cardiac involvement, defined as abnormal echocardiographic findings or arrhythmia. Collected clinical data were analyzed by Student's t-test or Fisher's exact test. Cardiac (N = 48, 50% male) versus no cardiac (N = 50, 50% male) were similar in age; weight; nonrespiratory symptoms; and medical history. The cardiac group had 1 death and symptoms including coronary artery dilation, ejection fraction <50%, pericardial effusion, peripheral edema, arrhythmia, and pulmonary artery thrombus. The cardiac group had higher risk of ICU admission (77% vs 54%, p = 0.02); invasive ventilation (23% vs 4%,p = 0.007); vasoactive infusions (27% vs 4%, p = 0.002); prominent respiratory symptoms (60% vs 36%, p < 0.03); abnormal chest imaging (69% vs 34%, p = 0.001); troponin (33% vs 12%, p = 0.01); alanine aminotransferase (33% vs 12%, p = 0.02); and thrombocytopenia (46% vs 22%, p = 0.02). Receiver operating curve analysis showed that abnormal laboratories had 94% sensitivity and 98% negative predictive value on the need for ICU interventions.Conclusion: In LATAM children with multisystem SARS COV2, cardiac involvement was prevalent. Cardiac involvement was more likely to require ICU interventions, certain abnormal labs, and respiratory involvement. What is Known: • SARS COV2 can be asymptomatic in children but in some cases can have serious multisystemic involvement. • Hispanic ethnicity is purportedly at high risk of SARS COV2 in nations where they are often disadvantaged minority populations. What is New: • Latin American children presenting with multisystem SARS COV2 frequently have cardiac involvement which was associated with ICU interventions; prominent respiratory symptoms; abnormal chest X-ray; elevated troponin, ALT, and thrombocytopenia. • Elevated troponin, ALT or thrombocytopenia had high sensitivity and negative predictive value on the need for intensive care interventions.

Cardiac manifestations in SARS-CoV-2-associated multisystem inflammatory syndrome in children: a comprehensive review and proposed clinical approach.

Initial reports on COVID-19 described children as largely spared from severe manifestations, with only 2-6% of children requiring intensive care treatment. However, since mid-April 2020, clusters of pediatric cases of severe systemic hyperinflammation and shock epidemiologically linked with COVID-19 have been reported. This condition was named as SARS-Cov-2-associated multisystem inflammatory syndrome in children and showed similarities to Kawasaki disease. Here, we present a narrative review of cases reported in literature and we discuss the clinical acute and follow-up management of these patients. Patients with SARS-Cov-2-associated multisystem inflammatory syndrome frequently presented with persistent fever, gastrointestinal symptoms, polymorphic rash, conjunctivitis, and mucosal changes. Elevated inflammatory markers and evidence of cytokine storm were frequently observed. A subset of these patients also presented with hypotension and shock (20-100%) from either acute myocardial dysfunction or systemic hyperinflammation/vasodilation. Coronary artery dilation or aneurysms have been described in 6-24%, and arrhythmias in 7-60%. Cardiac support, immunomodulation, and anticoagulation are the key aspects for the management of the acute phase. Long-term structured follow-up of these patients is required due to the unclear prognosis and risk of progression of cardiac manifestations.Conclusion: Multisystem inflammatory syndrome is a novel syndrome related to SARS-CoV-2 infection. Evidence is still scarce but rapidly emerging in the literature. Cardiac manifestations are frequent, including myocardial and coronary involvement, and need to be carefully identified and monitored over time. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) has been described associated with SARS-CoV-2. What is New: • Patients with MIS-C often present with fever, gastrointestinal symptoms, and shock. • Cardiac involvement is found in a high proportion of these patients, including ventricular dysfunction, coronary artery dilation or aneurysm, and arrhythmias. • Management is based on expert consensus and includes cardiac support, immunomodulatory agents, and anticoagulation. • Long-term follow-up is required due to the unclear prognosis and risk of progression of cardiac manifestation.

Coronary Artery Dilation in an Asymptomatic Pediatric Patient with COVID19 Antibodies.

We describe a 16-year-old asymptomatic male who presented with coronary artery dilation (z score + 2.3) identified on echo performed solely for presence of COVID-19 antibodies. This case raises the question of whether cardiac screening should be considered for all patients with a history of COVID-19.

Childhood Multisystem Inflammatory Syndrome: An Emerging Disease with Prominent Cardiovascular Involvement-A Scoping Review.

Multisystem inflammatory syndrome in children (MIS-C) or paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is an emerging disease in children affected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and thought to be an immune-mediated post-infectious complication of SARS-CoV-2. The disease presentation is similar to Kawasaki disease but has certain distinguishing features. The exact pathogenesis is still not clear but an aberrant immune response, antibody-mediated vascular damage and virus-mediated abnormal type I and III interferon-gamma response are thought to be responsible. Most children who are previously healthy present after 2-4 weeks of SARS-CoV-2 infections with febrile illness of short duration with prominent gastrointestinal, cardiac and hematologic manifestations, progressing to vasoplegic shock, requiring vasopressor therapy. Cardiovascular involvement is prominently marked by acute myocardial injury/myocarditis and the development of coronary artery aneurysms. Laboratory markers of inflammation are elevated uniformly. Most children require intensive care, and few need invasive ventilation. The treatment mainly consists of anti-inflammatory and immunomodulatory therapy like intravenous immunoglobulins and steroids. The overall prognosis is good and reported mortality rates are 0-4%.

Kawasaki Disease and Clinical Outcome Disparities Among Black Children.

OBJECTIVE: To determine whether Black children with Kawasaki disease exhibit disparities in prevalence, sequelae, and response to intravenous gamma globulin (IVIG) treatment. STUDY DESIGN: International Classification of Diseases codes were used to identify children with Kawasaki disease admitted to a tertiary center in the southeastern US. Subjects diagnosed and treated according to American Heart Association criteria were included. Demographic, laboratory, clinical, and echocardiographic data from the electronic medical record (2000-2015) were compared between Blacks and Whites. RESULTS: Data from 369 subjects (52% Whites and 48% Blacks) were included in our analysis. No significant differences related to timely admission, IVIG treatment, or coronary artery (CA) abnormalities during hospitalization were observed. Blacks showed lower IVIG response rates than Whites for patients administered IVIG within 10 days of fever onset (86.6% vs 95.6%; P = .007). Blacks received more ancillary drugs (9.6% vs 2.6%; P = .003), and endured longer hospitalizations (mean, 5 ± 3.9 days vs 3.4 ± 2.2 days; P = .001). Blacks presented with higher C-reactive protein level and erythrocyte sedimentation rate and lower hemoglobin, albumin, and sodium levels. Blacks had a higher proportion of persistent CA abnormalities than Whites at second follow-up echocardiogram (14.5% vs 6.3%; P = .03), and at third follow-up echocardiogram (21.2% vs 6.9%; P = .01). CONCLUSIONS: Compared with White children, Black children with Kawasaki disease had higher IVIG refractory prevalence, more severe inflammation, more ancillary treatments, and longer hospitalizations. Despite no racial differences in time to diagnosis or initial treatment, there was greater CA abnormality persistence among Black children at follow-up.

Longitudinal Echocardiographic Assessment of Coronary Arteries and Left Ventricular Function following Multisystem Inflammatory Syndrome in Children.

Myocardial dysfunction and coronary artery dilation have been reported in the acute setting of severe acute respiratory syndrome coronavirus disease-2-related multisystem inflammatory syndrome in children. Through a longitudinal echocardiographic single-center study of 15 children, we report the short-term outcomes of cardiac dysfunction and coronary artery dilation in severe acute respiratory syndrome coronavirus disease-2-related multisystem inflammatory syndrome in children.

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.