Dataset Information

Management of Multisystem Inflammatory Syndrome in Children Associated With COVID-19: A Survey From the International Kawasaki Disease Registry.

ABSTRACT:

Background

Since April 2020, there have been numerous reports of children presenting with systemic inflammation, often in critical condition, and with evidence of recent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to coronavirus disease 2019 (COVID-19), and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation.

Methods

We surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries.

Results

Among the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation. Every respondent reported use of intravenous immunoglobulin (IVIG), including 53% administering IVIG in all patients. Steroids were most often used for patients with severe clinical presentation or lack of response to IVIG, and only a minority used steroids in all patients (14%). Acetylsalicylic acid was frequently used among respondents (91%), including anti-inflammatory and/or antiplatelet dosing. Respondents reported use of prophylactic anticoagulation, especially in patients at higher risk for venous thromboembolism, and therapeutic anticoagulation, particularly for patients with giant coronary artery aneurysms.

Conclusions

There is variation in management of MIS-C patients, with suboptimal evidence to assess superiority of the various treatments; evidence-based gaps in knowledge should be addressed through worldwide collaboration to optimize treatment strategies.

SUBMITTER: Elias MD

PROVIDER: S-EPMC7484693 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening hyperinflammatory syndrome that occurs after primary SARS-CoV-2 infection. The pathogenesis of MIS-C remains undefined, and whether specific inflammatory biomarker patterns can distinguish MIS-C from other hyperinflammatory syndromes, including Kawasaki disease and macrophage activation syndrome (MAS), is unknown. Therefore, we aimed to investigate whether inflammatory biomarkers could be used to distinguish between these conditions.MethodsWe studied a prospective cohort of patients with MIS-C and Kawasaki disease and an established cohort of patients with new-onset systemic juvenile idiopathic arthritis (JIA) and MAS associated with systemic JIA (JIA-MAS), diagnosed according to established guidelines. The study was done at Cincinnati Children's Hospital Medical Center (Cincinnati, OH, USA). Clinical and laboratory features as well as S100A8/A9, S100A12, interleukin (IL)-18, chemokine (C-X-C motif) ligand 9 (CXCL9), and IL-6 concentrations were assessed by ELISA and compared using parametric and non-parametric tests and receiver operating characteristic curve analysis.FindingsBetween April 30, 2019, and Dec 14, 2020, we enrolled 19 patients with MIS-C (median age 9·0 years [IQR 4·5-15·0]; eight [42%] girls and 11 [58%] boys) and nine patients with Kawasaki disease (median age 2·0 years [2·0-4·0]); seven [78%] girls and two [22%] boys). Patients with MIS-C and Kawasaki disease had similar S100 proteins and IL-18 concentrations but patients with MIS-C were distinguished by significantly higher median concentrations of the IFNγ-induced CXCL9 (1730 pg/mL [IQR 604-6300] vs 278 pg/mL [54-477]; p=0·038). Stratifying patients with MIS-C by CXCL9 concentrations (high vs low) revealed differential severity of clinical and laboratory presentation. Compared with patients with MIS-C and low CXCL9 concentrations, more patients with high CXCL9 concentrations had acute kidney injury (six [60%] of ten vs none [0%] of five), altered mental status (four [40%] of ten vs none [0%] of five), shock (nine [90%] of ten vs two [40%] of five), and myocardial dysfunction (five [50%] of ten vs one [20%] of five); these patients also had higher concentrations of systemic inflammatory markers and increased severity of cytopenia and coagulopathy. By contrast, patients with MIS-C and low CXCL9 concentrations resembled patients with Kawasaki disease, including the frequency of coronary involvement. Elevated concentrations of S100A8/A9, S100A12, and IL-18 were also useful in distinguishing systemic JIA from Kawasaki disease with high sensitivity and specificity.InterpretationOur findings show MIS-C is distinguishable from Kawasaki disease primarily by elevated CXCL9 concentrations. The stratification of patients with MIS-C by high or low CXCL9 concentrations provides support for MAS-like pathophysiology in patients with severe MIS-C, suggesting new approaches for diagnosis and management.FundingCincinnati Children's Research Foundation, National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, the Deutsche Forschungsgemeinschaft, and The Jellin Family Foundation.

Project description:BackgroundRecent evidence shows an association between coronavirus disease 2019 (COVID-19) infection and a severe inflammatory syndrome in children. Cardiovascular magnetic resonance (CMR) data about myocardial injury in children are limited to small cohorts. The aim of this multicenter, international registry is to describe clinical and cardiac characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 using CMR so as to better understand the real extent of myocardial damage in this vulnerable cohort.Methods and resultsHundred-eleven patients meeting the World Health Organization criteria for MIS-C associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), having clinical cardiac involvement and having received CMR imaging scan were included from 17 centers. Median age at disease onset was 10.0 years (IQR 7.0-13.8). The majority of children had COVID-19 serology positive (98%) with 27% of children still having both, positive serology and polymerase chain reaction (PCR). CMR was performed at a median of 28 days (19-47) after onset of symptoms. Twenty out of 111 (18%) patients had CMR criteria for acute myocarditis (as defined by the Lake Louise Criteria) with 18/20 showing subepicardial late gadolinium enhancement (LGE). CMR myocarditis was significantly associated with New York Heart Association class IV (p = 0.005, OR 6.56 (95%-CI 1.87-23.00)) and the need for mechanical support (p = 0.039, OR 4.98 (95%-CI 1.18-21.02)). At discharge, 11/111 (10%) patients still had left ventricular systolic dysfunction.ConclusionNo CMR evidence of myocardial damage was found in most of our MIS-C cohort. Nevertheless, acute myocarditis is a possible manifestation of MIS-C associated with SARS-CoV-2 with CMR evidence of myocardial necrosis in 18% of our cohort. CMR may be an important diagnostic tool to identify a subset of patients at risk for cardiac sequelae and more prone to myocardial damage.Clinical trial registrationThe study has been registered on ClinicalTrials.gov, Identifier NCT04455347, registered on 01/07/2020, retrospectively registered.