Echocardiographic Findings in Pediatric Multisystem Inflammatory Syndrome Associated With COVID-19 in the United States

Abstract

Background Centers from Europe and United States have reported an exceedingly high number of children with a severe inflammatory syndrome in the setting of COVID-19, which has been termed multisystem inflammatory syndrome in children (MIS-C). Objectives This study aimed to analyze echocardiographic manifestations in MIS-C. Methods We retrospectively reviewed 28 MIS-C, 20 healthy controls and 20 classic Kawasaki disease (KD) patients. We reviewed echocardiographic parameters in acute phase of MIS-C and KD groups, and during subacute period in MIS-C group (interval: 5.2 ± 3 days). Results Only 1 case in MIS-C (4%) manifested coronary artery dilatation (z score=3.15) in acute phase, showing resolution during early follow up. Left ventricular (LV) systolic and diastolic function measured by deformation parameters, were worse in MIS-C compared to KD. Moreover, MIS-C patients with myocardial injury (+) were more affected than myocardial injury (-) MIS-C with respect to all functional parameters. The strongest parameters to predict myocardial injury in MIS-C were global longitudinal strain (GLS), global circumferential strain (GCS), peak left atrial strain (LAS) and peak longitudinal strain of right ventricular free wall (RVFWLS) (Odds ratio: 1.45 (1.08-1.95), 1.39 (1.04-1.88), 0.84 (0.73-0.96), 1.59 (1.09-2.34) respectively). The preserved LVEF group in MIS-C showed diastolic dysfunction. During subacute period, LVEF returned to normal (median: from 54% to 64%, p<0.001) but diastolic dysfunction persisted. Conclusions Unlike classic KD, coronary arteries may be spared in early MIS-C, however, myocardial injury is common. Even preserved EF patients showed subtle changes in myocardial deformation, suggesting subclinical myocardial injury. During an abbreviated follow-up, there was good recovery of systolic function but persistence of diastolic dysfunction and no coronary aneurysms. Condensed abstract Multisystem inflammatory syndrome in children (MIS-C) is an illness that resembles Kawasaki Disease (KD) or toxic shock, reported in children with a recent history of COVID-19 infection. This study analyzed echocardiographic manifestations of this illness. In our cohort of 28 MIS-C patients, left ventricular systolic and diastolic function were worse than in classic KD. These functional parameters correlated with biomarkers of myocardial injury. However, coronary arteries were typically spared. The strongest predictors of myocardial injury were global longitudinal strain, right ventricular strain, and left atrial strain. During subacute period, there was good recovery of systolic function, but diastolic dysfunction persisted.

Shock and Myocardial Injury in Children With Multisystem Inflammatory Syndrome Associated With SARS-CoV-2 Infection: What We Know. Case Series and Review of the Literature

“…Respiratory status was not significantly impacted in any patients included in our study, or in most of the literature reports of children with MIS-C, which describe similar incidence of MV than us, and mostly used in the context of shock for hemodynamic stabilization. 9,10,13,18 This finding contrasts with those of studies of adults 49 and with the report by Sun et al and Shekerdemian et al 6,8 in children with COVID-19 (not diagnosed with MIS-C), in whom the primary reason for PICU admission was respiratory distress. In our series, the 2 patients that required MV for stabilization showed mild to moderate respiratory distress, both had signs of fluid overload and atelectasis as evidenced on chest X-ray, and improved soon after the treatment was optimized.…”

“…32,33 Considering this, the increased inflammatory markers in our patients, and previous experience in adults with severe COVID-19, all received immunomodulatory drugs. This pattern of increased inflammatory markers has also been reported in most of the case series studies of children with MIS-C. [9][10][11][12][13]17,18 It has been reported that low-dose steroids might be beneficial for severe COVID-19, although this claim remains controversial. 34,35 Recently, a big randomized study from the RECOVERY collaborative group, reported preliminary results suggesting that dexamethasone reduces the 28-days mortality in adults with severe COVID-19 requiring hospitalization, mechanical ventilation or supplemental oxygen.…”

“…47,48 Probably based on that, and on the high levels of D-dimer found in children with MIS-C, anticoagulation therapy has been used inconsistently in some of these children and no adverse events have been highlighted in the literature, although the benefit of this therapy in this population remains unclear. 10,17,18 All of our patients showed elevated D-dimer levels, all received LMWH with no adverse events, and no one developed any thrombosis.…”

“…12 These studies have also reported increased values of cardiac troponin in most of the children with MIS-C as a marker of myocardial injury, with or without shock, as well as in our patients. 10,12,13,18 Ten (83%) of our patients were admitted due exclusively to shock and 2 (17%) to respiratory distress and shock. We observed initial characteristics of warm vasoplegic shock (distributive shock) in 8 patients (67%).…”

“…12 Use of anakinra has been poorly reported, although some institutions in Italy and Spain are enrolling adults with severe COVID-19 in clinical trials and it has also been used in children with MIS-C. 10,12,17,40,41 Human IVIG has also been proposed as a treatment for severe cases, considering its potential immunomodulatory effect and its safety profile, and children with inflammatory shock have been successfully treated with this therapy. [9][10][11][12][13]17,18,42,43 IVIG is also a treatment commonly used in KD, TSS and viral myocarditis. We used IVIG in 3 patients.…”