COVID-19 associated multisystem inflammatory syndrome in a neonate with atypical coronary artery involvement.

Objective The study aimed to report a COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) in a neonate found to have an atypical diffuse thickening in coronary artery walls, whose diagnosis required a multi-imaging approach. Study Design A neonate presented at birth with multiple organ involvement and coronary artery anomalies. A diagnosis of MIS-C associated to COVID-19 was supported by maternal Sars-CoV-2 infection during pregnancy, and by the presence of both IgG against Sars-CoV-2 and Spike-specific memory B cells response in the neonatal blood. Other plausible causes of the multiple organ involvement were excluded. Result At admission, a severe coronary artery dilatation was identified on echocardiography, supporting the diagnosis of MIS-C Kawasaki-like disease; however, coronary artery internal diameters were found to be normal using cardiac computed tomography angiography. At discharge, comparing the two imaging techniques each other, the correct diagnosis resulted to be an abnormal thickening in coronary arterial walls. These findings suggest that the inflammatory process affecting the coronary arterial wall in MIS-C could result not only in typical coronary artery lesions such as dilatation of the lumen or aneurysms development, but also in abnormal thickening of the coronary artery wall. Conclusion. Our case provides an alert for paediatric cardiologists about the complexity to assess coronary artery involvement in MIS-C, and raises the question of whether an abnormal vascular remodeling, with normal inner diameters, is to be considered like coronary artery dilatation for risk stratification.

1025. Prediction of Intravenous Immunoglobulin Resistance and Coronary Artery Dilatation in Kawasaki Disease: a Multicenter Study from Oman

Background Prediction of intravenous immunoglobulin (IVIG) resistance and coronary artery dilatation continues to be a challenge in the management of Kawasaki disease. Significant differences exist among different populations. Methods Children < 13 years of age who presented to the two main tertiary care hospitals in Oman (Royal Hospital and Sultan Qaboos University Hospital) between 2008 and 2019 with a diagnosis of Kawasaki disease were included. Diagnosis was confirmed and clinical, laboratory and echocardiography data was systematically collected and checked for accuracy. The primary outcome was the presence of IVIG resistance or coronary artery dilatation at the 6-week follow-up. Bivariate analysis was used to identify significant predictors of the primary outcome, followed by multivariable logistic regression to determine independent predictors. The Muscat Index of Kawasaki disease Severity (MIKS) score was created based on the results. Results 156 children with Kawasaki disease were included. Median age was 2.1 years (IQR 0.9-3.8), and 64% were males. All patients received IVIG, 26 (17%) received steroids, and one received infliximab. Coronary dilatation was identified in 41 (26%) patients on initial echocardiogram, and 26 (18%) at the 6-week follow-up visit. Variables significantly associated with the primary outcome were age ≤15 months (P=0.031), hemoglobin (P=0.009), WBC count (P=0.002), absolute neutrophil count (P=0.006), and CRP ≥150 mg/L (P=0.015). These variables in addition male gender (P=0.058), ALT >80 IU/L (P=0.10) and serum sodium (P=0.10), were entered into multivariable logistic regression. A predictive model based on CRP ≥150 mg/L (LR=2.2, P=0.049), male gender (LR=2.1, P=0.095) and WBC (LR=1.1, P=0.017) resulted, and it was used as basis for the MIKS score (Table 1). The MIKS score performed favorably to the Kobayashi score in its sensitivity to predict the primary outcome and its separate components (Table 2). Combining the MIKS score with other high-risk criteria had a sensitivity of 95% in predicting the primary outcome and a specificity of 56%. Table 1. Calculation of the Muscat Index of Kawasaki disease Severity (MIKS) score Table 2. Sensitivity, specificity and P value for the Kobayashi, MIKS, and combined high risk criteria in predicting IVIG resistance, coronary dilatation at 6 weeks, separately or in combination, among patients with Kawasaki disease. MIKS: Muscat Index of Kawasaki disease Severity. *High risk: presence of coronary artery dilatation on initial echocardiogram or age <1> Conclusion The MIKS score predicts IVIG resistance and coronary artery dilatation in Kawasaki disease in our setting, with favorable performance compared to the Kobayashi score. Disclosures All Authors: No reported disclosures

Ultrasonic Diagnostic Strategy for the Causes of Coronary Artery Dilatation in Infants

Objective:To explore a differential diagnosis strategy for the causes of coronary artery dilatation (CAD) in infants．Methods: Clinical and echocardiography data for 243 infants with CAD from the Shengjing Hospital of China Medical University were analyzed retrospectively. The patients were divided into congenital and acquired groups according to the CAD causes.Results: The lesion detection rate for CAD in 22,925 infants who underwent echocardiography was 1.06% (243/22,925). The acquired group accounted for 84.77% (206/243) of participants, all of which had Kawasaki disease. The congenital group accounted for 15.23% (37/243) of patients, including coronary artery fistula [12.35% (30/243)], anomalous origin of the coronary artery [2.06% (5/243)], severe pulmonary stenosis [0.41% (1/243)], and moderate aortic stenosis [0.41% (1/243)]. There was no significant difference in the Z-score for CAD between the two groups of children (P>0.05). There were differences in the scope and shape of CAD between the two groups (all P<0. 05). Acquired causes mainly manifested as segmental dilatation, while congenital causes manifested as tubular dilatation. The sensitivity and specificity of segmental dilatation in predicting acquired causes were 97.57% and 100%, respectively, and that of tubular dilatation in predicting congenital causes were 97.30% and 98.06%, respectively. Conclusion: It is particularly important to diagnose the cause of CAD because its treatment depends on its etiology. When an echocardiography examination identifies CAD in infants, comprehensive and systematic analysis can quickly and accurately determine the cause of CAD according to the diagnostic strategy process and evaluation of dilatation and cardiac structure characteristics.

Kawasaki Disease and Systemic Juvenile Idiopathic Arthritis – Two Ends of the Same Spectrum

Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (sJIA) are two distinct systemic inflammatory diseases of childhood. Each diagnosis is based on criteria, but numerous clinical features are overlapping. As no specific diagnostic tests are available, differentiation between both disease entities can be challenging. Here, we describe the disease course of patients with co-diagnosis of both KD and sJIA (KD/sJIA). All our KD (n = 1765) and sJIA (n = 112) cases were critically reviewed for co-diagnosis of KD/sJIA. Eight KD/sJIA cases were identified and their clinical presentation, treatment regimens, coronary artery outcome and complications are herein described. Each KD/sJIA patient fulfilled diagnostic criteria for KD and for sJIA. Ongoing fever, rash and arthritis were present in each patient. The KD/sJIA patients had recalcitrant KD requiring multiple doses of intravenous immunoglobulin and steroids. Five patients had coronary artery dilatation at KD diagnosis, which resolved in all by 6 weeks. Pericardial effusion was present in 5 patients. One KD/sJIA patient developed macrophage activation syndrome. In conclusion, a small proportion (0.5%) of our KD patients evolved into sJIA, and 7% of our sJIA population presented initially as KD. KD/sJIA patients were characterized by a recalcitrant KD course and a high prevalence of coronary artery dilatation. Patients with co-diagnoses may provide a clue to potentially shared immunopathology in KD and sJIA, leading us to posit that both entities may be part of the same clinical spectrum.

Clinical analysis of chronic active EBV infection with coronary artery dilatation and a matched case–control study

Objective To investigate the clinical characteristics, treatment, prognosis and risk factors for chronic active Epstein–Barr Virus infection (CAEBV) associated with coronary artery dilatation (CAD) in children. Methods Children with CAEBV associated with CAD hospitalized at Beijing Children’s Hospital, Capital Medical University from March 2016 to December 2019 were analyzed. Children with CAEBV without CAD were selected as the control group and matched by sex, age, treatment and admission time. The clinical manifestations, laboratory and ultrasound examinations, treatment and prognosis of the children were collected in both groups. Results There were 10 children with CAEBV combined with CAD, including 6 males and 4 females, accounting for 8.9% (10/112) of CAEBV patients in the same period, with an onset age of 6.05 (2.8–14.3) years. The median follow-up time was 20 (6–48) months. All the patients had high copies of EBV-DNA in whole blood [1.18 × 107 (1.90 × 105–3.96 × 107) copies/mL] and plasma [1.81 × 104 (1.54 × 103–1.76 × 106) copies/mL], and all biopsy samples (bone marrow, lymph nodes or liver) were all positive for Epstein–Barr virus-encoded small RNA. Among the 10 children, 8 had bilateral CAD, and 2 patients had unilateral CAD. After diagnosis, 7 children were treated with L-DEP chemotherapy in our hospital. After chemotherapy, four patients underwent allogeneic hematopoietic stem cell transplantation (HSCT). The others were waiting for HSCT. At the time of the last patients follow up record, the CAD had returned to normal in 3 patients, and the time from the diagnosis of CAD to recovery was 21 (18–68) days. LDH, serum ferritin, TNF-α and IL-10 levels were statistically significantly different between the two groups (P = 0.009, 0.008, 0.026 and 0.030). There were no significant differences in survival rate between the two groups (P = 0.416). Conclusion The incidence of CAEBV with CAD was low. CAEBV with CAD did not influence the prognosis. Patients who had high LDH, serum ferritin, TNF-α, and IL-10 levels early in their illness were more likely to develop CAD.

Clinical Analysis of Chronic Active EBV Infection with Coronary Artery Dilatation and Matched Case-control Study

Objective To investigate the clinical characteristics, treatment, prognosis, and risk factors of chronic active EBV infection (CAEBV) associated with coronary artery dilatation (CAD) in children.Methods Children with CAEBV associated with CAD hospitalized in Beijing Children’s Hospital, Capital Medical University, from March 2016 to December 2019 were analyzed. At the same time, children with CAEBV without CAD were selected as the control group, matched by sex, age, treatment and admission time. The clinical manifestations, laboratory and ultrasonic examinations, treatment and prognosis of the children were collected in both groups.Results There were 10 children with CAEBV combined with CAD, accounting for 8.9% (10/112) of CAEBV patients at the same period, which including 6 males and 4 females, with onset age of 6.05 (2.8-14.3) years. The median follow-up time was 20 (6-48) months. All the patients had high copies of EBV-DNA in whole blood 1.18x107（1.90x105-3.96x107）copies/mL and plasma 1.81x104（1.54x103-1.76x106）copies/mL, and the Epstein-Barr virus encoded small RNA in biopsy was all positive. Among the 10 children, 8 had bilateral CAD, with 2 patients unilateral. After diagnosis, 7 children were treated with L-DEP chemotherapy in our hospital. After chemotherapy, four patients accepted allo-genetic Hematopoietic Stem Cell Transplantation (HSCT). The others were waiting for HSCT. By the end of the follow-up, CAD had returned to normal in 3 patients, and the time from diagnosis of CAD to recovery was 21 (18-68) d. The level of LDH, serum ferritin, TNF-α and IL-10 had statistically significant difference between the two groups (P=0.009, 0.008, 0.026 and 0.030). There were no significant differences in survival rate between the two groups (P=0.416).Conclusion The incidence of CAEBV with CAD was low. CAEBV with CAD did not influence the prognosis. Patients with CAEBV had high LDH, serum ferritin, TNF-α and IL-10 in the early onset were prone to have CAD.

Multimodality cardiac evaluation in children and young adults with multisystem inflammation associated with COVID-19

Aims Following the peak of the UK COVID-19 epidemic, a new multisystem inflammatory condition with significant cardiovascular effects emerged in young people. We utilized multimodality imaging to provide a detailed sequential description of the cardiac involvement. Methods and Results Twenty consecutive patients (mean age 10.6 ± 3.8 years) presenting to our institution underwent serial echocardiographic evaluation on admission (median day 5 of illness), the day coinciding with worst cardiac function (median day 7), and the day of discharge (median day 15). We performed cardiac computed tomography (CT) to assess coronary anatomy (median day 15) and cardiac magnetic resonance imaging (CMR) to assess dysfunction (median day 20). On admission, almost all patients displayed abnormal strain and tissue Doppler indices. Three-dimensional (3D) echocardiographic ejection fraction (EF) was &lt;55% in half of the patients. Valvular regurgitation (75%) and small pericardial effusions (10%) were detected. Serial echocardiography demonstrated that the mean 3D EF deteriorated (54.7 ± 8.3% vs. 46.4 ± 8.6%, P = 0.017) before improving at discharge (P = 0.008). Left main coronary artery (LMCA) dimensions were significantly larger at discharge than at admission (Z score –0.11 ± 0.87 vs. 0.78 ± 1.23, P = 0.007). CT showed uniform coronary artery dilatation commonly affecting the LMCA (9/12). CMR detected abnormal strain in all patients with global dysfunction (EF &lt;55%) in 35%, myocardial oedema in 50%, and subendocardial infarct in 5% (1/20) patients. Conclusions Pancarditis with cardiac dysfunction is common and associated with myocardial oedema. Patients require close monitoring due to coronary artery dilatation and the risk of thrombotic myocardial infarction.