Advanced Echocardiographic Analysis in Medium-Term Follow-Up of Children with Previous Multisystem Inflammatory Syndrome.

Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory disease related to SARS-CoV2 infection, with frequent cardiovascular involvement in the acute setting. The aim of the study was to evaluate the cardiac function at 6 months. Thirty-two patients diagnosed with MIS-C were enrolled and underwent advanced echocardiogram at discharge and at 6 months. According to the left ventricular ejection fraction (LVEF) at admission, the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥ 45%) and the follow-up results were compared. At discharge, all patients had normal LV and RV systolic function (LVEF 61 ± 4.4%, LV global longitudinal strain -22.1%, TAPSE 20.1mm, s' wave 0.13m/s, RV free wall longitudinal strain -27.8%) with normal LV diastolic function (E/A 1.5, E/e' 5.7, and left atrial strain 46.5%) and no significant differences at 6 months. Compared to group B, the group A patients showed a reduced, even if normal, LV global longitudinal strain at discharge (-21.1% vs. -22.6%, p-value 0.02), but the difference was no longer significant at the follow-up. Patients with MIS-C can present with depressed cardiac function, but if treated, the cardiac function recovered without late onset of cardiac disease. This favorable result was independent of the severity of acute LV dysfunction.

Six-month multidisciplinary follow-up in multisystem inflammatory syndrome in children: An Italian single-center experience.

Background: A severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 has been described after infection. A limited number of reports have analyzed the long-term complications related to pro-inflammatory status in MIS-C. We evaluated multiorgan impairment at the 6-month follow-up in MIS-C. Methods: We enrolled 33 pediatric patients consecutively hospitalized for MIS-C and monitored for almost 6 months. The inter-relationship of patient's features and disease severity at admission with long term complications was studied by multivariate analysis. Results: Endo-metabolic derangement, cardiac injury, respiratory, renal and gastrointestinal manifestations and neurological involvement are part of the initial presentation. The most abnormalities appear to resolve within the first few weeks, without significant long term dysfunction at the 6-months follow-up, except for endocrine (non-thyroidal illness syndrome in 12.1%, insulin resistance in 21.2%) and neurological system (27.3% cognitive or psychological, behavioral, adaptive difficulties). Endocrine and heart involvement at admission represent a significant factor on the long term sequelae; however no association between severity score and long-term outcome was noted. Conclusions: The severity of initial clinical presentation may be associated to organ domain, however it is not related to long term sequelae. The prevalent organ restoration supports a predominant indirect immune-mediated injury triggered by a systemic inflammatory response; however a direct damage due to the viral entry could be not excluded. Eventhought our preliminary results seem to suggest that MIS-C is not a long-term risk condition for children health, a longer follow-up is mandatory to confirm this hypothesis.

Longitudinal Anthropometry and Body Composition in Children With SARS-CoV-2-Associated Multisystem Inflammatory Syndrome.

OBJECTIVES: Acute coronavirus disease 2019 infection has been shown to negatively affect body composition among adult and malnourished or obesity children. Our aim is to longitudinally evaluate body composition in children affected by the Multisystem Inflammatory Syndrome (MIS-C). METHODS: In this cohort study, we recruited 40 patients affected by MIS-C, aged 2-18 years old, who were admitted in our clinic between December 2020 and February 2021. Physical examination for each participant included weight, height, body mass index (BMI) z score, circumferences, and skinfolds assessment. The same measurements were repeated during outpatient follow-up at 10 (T2), 30 (T3), 90 (T4), and 180 (T5) days after hospital discharge. Fat mass and fat free mass were calculated according to skinfolds predictive equations for children and adolescents. A control group was randomly selected among patients attending a pediatric nutritional outpatient clinic. RESULTS: BMI z score significantly decrease between preadmission and hospital discharge. Similarly, arm circumference z score, arm muscular area z score, and arm fat area z score significantly decreased, during hospital stay. Fat mass index (FMI) significantly increased over time, peaking at T3. Fat free mass index decreased during hospitalization. CONCLUSIONS: To the best of our knowledge, this is the first study to assess body composition in a numerically large pediatric MIS-C population from acute infection to 6 months after triggering event. FMI and anthropometric parameters linked to fat deposits were significantly higher 6 months after acute event. Thus, limiting physical activity and having sedentary lifestyle may lead to an accumulation of adipose tissue even in healthy children who experienced MIS-C and long hospitalization.

Advanced Echocardiographic Analysis in Medium-Term Follow-Up of Children with Previous Multisystem Inflammatory Syndrome

Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory disease related to SARS-CoV2 infection, with frequent cardiovascular involvement in the acute setting. The aim of the study was to evaluate the cardiac function at 6 months. Thirty-two patients diagnosed with MIS-C were enrolled and underwent advanced echocardiogram at discharge and at 6 months. According to the left ventricular ejection fraction (LVEF) at admission, the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥45%) and the follow-up results were compared. At discharge, all patients had normal LV and RV systolic function (LVEF 61 ±4.4%, LV global longitudinal strain −22.1%, TAPSE 20.1mm, s' wave 0.13m/s, RV free wall longitudinal strain −27.8%) with normal LV diastolic function (E/A 1.5, E/e' 5.7, and left atrial strain 46.5%) and no significant differences at 6 months. Compared to group B, the group A patients showed a reduced, even if normal, LV global longitudinal strain at discharge (−21.1% vs. −22.6%, p-value 0.02), but the difference was no longer significant at the follow-up. Patients with MIS-C can present with depressed cardiac function, but if treated, the cardiac function recovered without late onset of cardiac disease. This favorable result was independent of the severity of acute LV dysfunction.

Blood Fatty Acids Profile in MIS-C Children.

MIS-C (multisystem inflammatory syndrome in children) linked to SARS-CoV-2 infection, is a pathological state observed in subjects younger than 21 years old with evidence of either current SARS-CoV-2 infection or exposure within the 4 weeks prior to the onset of symptoms, the presence of documented fever, elevated markers of inflammation, at least two signs of multisystem involvement, and, finally, lack of an alternative diagnosis. They share with adult COVID-19 patients the presence of altered markers of inflammation, but unlike most adults the symptoms are not pulmonary but are affecting several organs. Lipid mediators arising from polyunsaturated fatty acids (PUFA) play an important role in the inflammatory response, with arachidonic acid-derived compounds, such as prostaglandins and leukotrienes, mainly pro-inflammatory and ω3 PUFA metabolites such as resolvins and protectins, showing anti-inflammatory and pro-resolution activities. In order to assess potential alterations of these FA, we evaluated the blood fatty acid profile of MIS-C children at admission to the hospital, together with biochemical, metabolic and clinical assessment. All the patients enrolled showed altered inflammatory parameters with fibrinogen, D-dimer, NT-proBNP, ferritin, aspartate aminotransferase (AST), C-reactive protein (CRP) and TrygIndex levels over the reference values in all the subjects under observation, while albumin and HDL-cholesterol resulted below the normal range. Interestingly, linoleic acid (LA), arachidonic acid (AA) and the ω3 PUFA docosahexaenoic acid (DHA) results were lower in our study when compared to relative amounts reported in the other studies, including from our own laboratory. This significant alteration is pointing out to a potential depletion of these PUFA as a result of the systemic inflammatory condition typical of these patients, suggesting that LA- and AA-derived metabolites may play a critical role in this pathological state, while ω3 PUFA-derived pro-resolution metabolites in these subjects may not be able to provide a timely, physiological counterbalance to the formation of pro-inflammatory lipid mediators. In conclusion, this observational study provides evidence of FA alterations in MIS-C children, suggesting a significant contribution of ω6 FA to the observed inflammatory state, and supporting a potential dietary intervention to restore an appropriate balance among the FAs capable of promoting the resolution of the observed inflammatory condition.

Acute encephalitis in pediatric multisystem inflammatory syndrome associated with COVID-19.

OBJECTIVE: To characterize neurological involvement in multisystem inflammatory syndrome in children (MIS-C) related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Retrospective analysis of the clinical, electroencephalographic, CSF and neuroradiological parameters recorded in seven children (3 males, aged 3-10 years) affected by MIS-C with acute neurological involvement. RESULTS: All cases presented acute encephalopathy with drowsiness, irritability, mood deflection and diffuse EEG slowing with periodic posterior complexes. Focal neurological signs, normal brain MRI and CSF, were present in four patients; these patients received intravenous methylprednisolone at 30 mg/kg/day for 3 days. In all cases, the clinical picture rapidly improved in the first three days, and all neurological symptoms and EEG abnormalities disappeared within 10 and 30 days respectively. The severity and duration of the EEG abnormalities was proportional to the extent of the neurological involvement. CONCLUSIONS: Patients with MIS-C may present acute encephalitis characterized by rapid-onset encephalopathy and EEG abnormalities (slow wave activity and/or epileptic abnormalities), in some cases associated with focal neurological signs that disappear with immunomodulatory therapy. The detection through neurological evaluation of sentinel neurological signs and distinctive EEG patterns documentable at disease onset will allow timely diagnosis and treatment of these cases.

Impaired Glucose-Insulin Metabolism in Multisystem Inflammatory Syndrome Related to SARS-CoV-2 in Children.

An interaction between metabolic glucose impairment and coronavirus disease 2019 is reported. The development of a severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection has been described. We evaluated the impact of MIS-C on glycemic patterns in pediatric patients. A group of 30 children and adolescents affected by MIS-C were considered; all patients were normal weight. Clinical and biochemical assessments, including surrogate markers of insulin resistance (IR) such as homeostasis model analysis-IR (HOMA-IR) and triglyceride-glucose (TyG) indexes, were recorded. Patients were also invited to undergo an intermittently scanned continuous glucose monitoring (isCGM). HOMA-IR index was calculated in 18 patients (60%), of which 17 (94%) revealed a pathological value. TyG index was computed for all patients and pathological values were detected in all cases. In 15 patients, isCGM data were recorded on average for 9 days (±3 days). Overall, average glucose was 105 mg/dL (±16 mg/dL) and average time spent in the 70-180 mg/dL range (TIR) was 93.76%, with nearly 10% of glucose readings in the 141-180 mg/dL range; glycemic fluctuations over the hyperglycemic threshold were detected in four patients. Regular glucose monitoring may be useful to prevent metabolic imbalance and obtain a better outcome.

Children With Inflammatory Bowel Disease in the COVID-19 Main Endemic Focus: The Lombardy Experience.

Objectives: In the era of Coronavirus 2019 (COVID-19), concern has been raised for immunosuppressed patients, including children with inflammatory bowel diseases (IBD). We aimed to collect data from IBD tertiary centers of Lombardy during pandemic. Methods: A cross-sectional survey enrolling IBD children has been completed by seven major IBD centers in Lombardy during lockdown. The clinical form included questions on any symptom consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the IBD adherence treatment. Furthermore, we have reviewed all IBD medical records including new IBD diagnoses and flares in known IBD patients after the lockdown. Results: Questionnaires of 290 IBD children were returned during lockdown. Out of them, 24 children (8%) complained of mild symptoms suspicious of SARS-CoV-2 infection without needing hospitalization or changing IBD treatment. During the lockdown, one patient presented with IBD flare and one had infectious colitis, with no new IBD cases. Conversely, after lockdown, 12/290 (4%) children relapsed and 15 children were newly diagnosed with IBD. Last year, in the same timeframe, 20/300 (7%) children presented with IBD flare, while 17 children had IBD onset with no statistical difference. Conclusions: Our data on children with IBD in a high COVID-19 prevalence region are reassuring. Only a minority of IBD children had mild symptoms, and no hospitalization or treatment modification was needed. Standard IBD treatments including biologics were safely continued. New IBD diagnoses and flares in known IBD children occurred after the lockdown phase, although no significant difference was found compared with the previous year.

How to Manage COVID-19 Vaccination in Immune-Mediated Inflammatory Diseases: An Expert Opinion by IMIDs Study Group.

Since March 2020, the outbreak of Sars-CoV-2 pandemic has changed medical practice and daily routine around the world. Huge efforts from pharmacological industries have led to the development of COVID-19 vaccines. In particular two mRNA vaccines, namely the BNT162b2 (Pfizer-BioNTech) and the mRNA-1273 (Moderna), and a viral-vectored vaccine, i.e. ChAdOx1 nCoV-19 (AstraZeneca), have recently been approved in Europe. Clinical trials on these vaccines have been published on the general population showing a high efficacy with minor adverse events. However, specific data about the efficacy and safety of these vaccines in patients with immune-mediated inflammatory diseases (IMIDs) are still lacking. Moreover, the limited availability of these vaccines requires prioritizing some vulnerable categories of patients compared to others. In this position paper, we propose the point of view about the management of COVID-19 vaccination from Italian experts on IMIDs and the identification of high-risk groups according to the different diseases and their chronic therapy.