This report describes the epidemiology and clinical course of patients younger than 21 years of age from 26 states who had multisystem inflammatory syndrome. Many were infected with SARS-CoV-2 at ...least 1 to 2 weeks before syndrome onset. The median age of the patients was 8.3 years, and 73% were previously healthy.
IMPORTANCE: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. OBJECTIVE: To compare clinical characteristics and outcomes ...of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). SETTING, DESIGN, AND PARTICIPANTS: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase–polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. EXPOSURE: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. RESULTS: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference RD, 21.4% 95% CI, 16.1%-26.7%; aRR, 1.51 95% CI, 1.33-1.72 vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% 95% CI, 5.6%-16.0%; aRR, 1.43 95% CI, 1.17-1.76 vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% 95% CI, 42.4%-52.0%; aRR, 2.99 95% CI, 2.55-3.50 vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% 95% CI, 4.7%-10.6%; aRR, 2.49 95% CI, 2.05-3.02 vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% 95% CI, 2.3%-7.3%; aRR, 2.29 95% CI, 1.84-2.85 vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL 212/523 {41%} vs 84/486 {17%}, P < .001). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. CONCLUSIONS AND RELEVANCE: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.
Background
The natural history of coronary artery aneurysms (CAA) after intravenous immunoglobulin (IVIG) treatment in the United States is not well described. We describe the natural history of CAA ...in US Kawasaki disease (KD) patients and identify factors associated with major adverse cardiac events (MACE) and CAA regression.
Methods and Results
We evaluated all KD patients with CAA at 2 centers from 1979 to 2014. Factors associated with CAA regression, maximum CA z‐score over time (zMax), and MACE were analyzed. We performed a matched analysis of treatment effect on likelihood of CAA regression. Of 2860 KD patients, 500 (17%) had CAA, including 90 with CAA z‐score >10. Most (91%) received IVIG within 10 days of illness, 32% received >1 IVIG, and 27% received adjunctive anti‐inflammatory medications. CAA regression occurred in 75%. Lack of CAA regression and higher CAA zMax were associated with earlier era, larger CAA z‐score at diagnosis, and bilateral CAA in univariate and multivariable analyses. MACE occurred in 24 (5%) patients and was associated with higher CAA z‐score at diagnosis and lack of IVIG treatment. In a subset of patients (n=132) matched by age at KD and baseline CAA z‐score, those receiving IVIG plus adjunctive medication had a CAA regression rate of 91% compared with 68% for the 3 other groups (IVIG alone, IVIG ≥2 doses, or IVIG ≥2 doses plus adjunctive medication).
Conclusions
CAA regression occurred in 75% of patients. CAA z‐score at diagnosis was highly predictive of outcomes, which may be improved by early IVIG treatment and adjunctive therapies.
Background
Children with single ventricle heart disease require frequent interventions and follow‐up. Low socioeconomic status (SES) may limit access to high‐quality care and place these children at ...risk for poor long‐term outcomes.
Methods and Results
Data from the SVR (Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use) data set were used to examine the relationship of US neighborhood SES with 30‐day and 1‐year mortality or cardiac transplantation and length of stay among neonates undergoing the Norwood procedure (n=525). Crude rates of death or transplantation at 1 year after Norwood were highest for patients living in neighborhoods with low SES (lowest tertile 37.0% versus middle tertile 31.0% versus highest tertile 23.6%, P=0.024). After adjustment for patient demographics, birth characteristics, and anatomy, patients in the highest SES tertile had significantly lower risk of death or transplant than patients in the lowest SES tertile (hazard ratio 0.62, 95% confidence interval, 0.40, 0.96). When SES was examined continuously, the hazard of 1‐year death or transplant decreased steadily with increasing neighborhood SES. Hazard ratios for 30‐day transplant‐free survival and 1‐year transplant‐free survival were similar in magnitude. There were no significant differences in length of stay following the Norwood procedure by SES.
Conclusions
Low neighborhood SES is associated with worse 1‐year transplant‐free survival after the Norwood procedure, suggesting that socioeconomic and environmental factors may be important determinants of outcome in critical congenital heart disease. Future studies should investigate aspects of SES and environment amenable to intervention.
Clinical Trial Registration
URL:http://www.clinicaltrials.gov> http://www.clinicaltrials.gov. Unique identifier: NCT00115934.
Intravenous immunoglobulin (IVIg) is a purified plasma product that is used for many immune‐deficient conditions and autoimmune conditions. Use of IVIg for treatment for Kawasaki disease (KD) is ...critical for control of inflammation. The American Heart Association (AHA) recommends a single infusion of 2 g/kg preferably given during the first 10 days of illness. In this review, we have discussed the possible mechanisms of action of IVIg in KD and its clinical usage in this condition.
Hypoplastic left heart syndrome is a complex congenital heart lesion that requires a three-stage procedure for surgical palliation. This clinical trial examines two approaches to the first stage of ...the procedure, and the results provide important guidance for the most appropriate surgical management of this serious lesion.
This clinical trial examines two approaches to the first stage of the Norwood procedure, and the results provide important guidance for the most appropriate surgical management of this serious lesion.
Hypoplastic left heart syndrome and related anomalies involving a single right ventricle are characterized by hypoplasia of the left heart and the aorta, with compromised systemic cardiac output (Figure 1). Infants with the syndrome generally undergo a three-stage reconstruction culminating in the Fontan procedure. The first operation (stage I) is the Norwood procedure, in which the right ventricle is connected to a reconstructed aorta with the use of the proximal main pulmonary artery for systemic outflow. Pulmonary blood flow is reestablished by means of a shunt from the pulmonary artery to the systemic circulation. In the second operation (stage II), . . .
Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) characterised by a vicious cycle of immune amplification that can culminate in ...overwhelming inflammation and multiorgan failure. The clinical features of MAS overlap with those of active sJIA, complicating early diagnosis and treatment. We evaluated adenosine deaminase 2 (ADA2), a protein of unknown function released principally by monocytes and macrophages, as a novel biomarker of MAS.
We established age-based normal ranges of peripheral blood ADA2 activity in 324 healthy children and adults. We compared these ranges with 173 children with inflammatory and immune-mediated diseases, including systemic and non-systemic JIA, Kawasaki disease, paediatric systemic lupus erythematosus and juvenile dermatomyositis.
ADA2 elevation beyond the upper limit of normal in children was largely restricted to sJIA with concomitant MAS, a finding confirmed in a validation cohort of sJIA patients with inactive disease, active sJIA without MAS or sJIA with MAS. ADA2 activity strongly correlated with MAS biomarkers including ferritin, interleukin (IL)-18 and the interferon (IFN)-γ-inducible chemokine CXCL9 but displayed minimal association with the inflammatory markers C reactive protein and erythrocyte sedimentation rate. Correspondingly, ADA2 paralleled disease activity based on serial measurements in patients with recurrent MAS episodes. IL-18 and IFN-γ elicited ADA2 production by peripheral blood mononuclear cells, and ADA2 was abundant in MAS haemophagocytes.
These findings collectively identify the utility of plasma ADA2 activity as a biomarker of MAS and lend further support to a pivotal role of macrophage activation in this condition.
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