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Cardiovascular involvement in Multisystem Inflammatory Syndrome in Children (MIS-C), a potential consequence of coronavirus disease-2019 (COVID-19), is common. Conventional transthoracic echocardiography (TTE) provides primary data on the function of the left and right ventricles, while Speckle Tracking Echocardiography (STE) is more sensitive. This study aims to assess longitudinal cardiac function using STE in these patients. This longitudinal study was conducted from late 2021 to early 2022 at Imam Hossein Children's Hospital, Isfahan. Cardiac function was assessed by STE at the time of diagnosis and again two months later. Demographics, clinical characteristics, ECG interpretations, imaging studies, and serum cardiac marker levels were collected. Thirty-five pediatric patients with a mean age of 5.1 years (range: 4 months to 17 years) were included and prospectively followed. Twenty-nine of them, comprising 14 males (48.3%) and 15 females (51.7%), underwent STE and were compared with 29 healthy age- and sex-matched children. Factors related to adverse events included reduced myocardial function, enlarged left atrium or ventricle, and mitral regurgitation (MR). Patients with comorbidities affecting strain measurements were excluded from the strain analyses. A significant difference was observed between the groups in regional strains in the basal and apical septal and middle lateral regions. Global strain rate (GLS) and strain rates were not significantly different but were still lower than the control group. Twenty percent of patients had abnormal GLS but normal left ventricular ejection fraction (LVEF). All patients exhibited reduced segmental myocardial strain in at least one segment. Four out of 26 recovered patients without comorbidities had abnormal GLS at follow-up, despite normal LVEF. STE proves more useful than conventional echocardiography in patients with MIS-C, revealing subclinical cardiac injury in the acute and post-acute phases. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-COVID condition due to a delayed hyperimmune response to SARS-CoV-2. High-density lipoproteins (HDL) are pivotal players in inflammatory and immune modulation through the remodeling of their subfractions. Methods: This study aimed to evaluate serum levels of cholesterol, HDL, and HDL subfractions (HDL-SUB) to define their role in the pathogenesis of MIS-C and their potential use as biomarkers of this condition. We analyzed serum cholesterol, HDL and HDL-SUB (by capillary electrophoresis) in relation to serum values of biomarkers of inflammation and endothelial damage (by microfluidic immunoassays) in 48 patients with MIS-C at hospital admission and in 48 age- and sex-matched healthy controls. Results: Serum cholesterol, as well as HDL, were significantly lower in MIS-C patients than controls. Serum cholesterol was inversely correlated with all biomarkers of inflammation, confirming the impact of cytokines on reverse cholesterol transport, whereas HDL values were inversely correlated with serum biomarkers of endothelial damage, suggesting a role of HDL in endothelial damage in MIS-C patients. Furthermore, we found a remodeling of HDL-SUB with a more pronounced decrease in small HDL that have anti-inflammatory activity. Conclusions: These data confirm the severe impairment of reverse cholesterol transport in MIS-C and indicate serum HDL and HDL-SUB as potential useful diagnostic biomarkers of MIS-C. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication arising from SARS-CoV-2 infection, with indications that rare inborn errors of immunity may play a role in its pathogenesis. Recent studies suggest that genetic predispositions, particularly monogenic forms, could significantly influence the immune responses to SARS-CoV-2 in MIS-C. Methods: We analysed 24 children under 12 years old, all of whom met the criteria provided by the World Health Organization, 2020 for MIS-C diagnosis, from the Paediatric COVID-19 Registry in Kuwait (PCR-Q8). Demographic and clinical data were collected from medical records, and exome sequencing was performed on the children and their parents to identify rare exonic variants. These variants were prioritized using two approaches: a candidate genes approach employing trio segregation analysis, and a candidate variants approach using a gene panel informed by previous studies on MIS-C-related genetic variants and datasets of differentially expressed genes in MIS-C patients. Results: The candidate genes approach identified 53 unique genes in 20 of the 24 probands, including DDX60 and TMEM154 , which were also differentially expressed between MIS-C and control groups. The candidate variants approach identified 33 rare, predicted deleterious heterozygous variants across 19 unique genes in 19 of the 24 probands, including both previously described and novel candidate variants for MIS-C. Pathway analysis of the identified genes from both approaches revealed significant involvement in immune response, viral defence, and inflammatory pathways. Conclusion: This study underscores the monogenic susceptibility to MIS-C, enhancing the evidence base through comprehensive genetic analysis. The findings highlight the critical role of genetic predispositions in MIS-C and suggest that further functional genomics work is necessary to explore the mechanistic contributions of these genes, facilitating the development of targeted diagnostic strategies. [ABSTRACT FROM AUTHOR]

The document "COVID-19: Lessons Learned from Molecular and Clinical Research" published in the International Journal of Molecular Sciences discusses the identification and management of the SARS-CoV-2 virus, the etiological agent of COVID-19. It highlights the importance of developing accurate molecular tests, identifying biomarkers for patient stratification, and monitoring disease evolution through genomic surveillance. The document also addresses the emergence of long COVID or post-acute COVID-19 syndrome, emphasizing the need for targeted research and effective therapies to manage this complex clinical condition. Additionally, it underscores the ongoing efforts to deepen the understanding of COVID-19 pathogenesis and clinical evolution. [Extracted from the article]

Background: Multisystem inflammatory syndrome in children (MIS-C) presents some clinical overlap with Kawasaki disease (KD). Although KD is common in Japan, the clinical characteristics of MIS-C in Japan remain unknown. Therefore, we aimed to determine the epidemiological and clinical features of MIS-C in Japan. Methods: Using a case reporting form, a nationwide registry was created between November 2020 and March 2023, involving 2,080 facilities throughout Japan. We prospectively and retrospectively enrolled patients with MIS-C. The primary outcomes were the number and incidence rates of children with MIS-C. The secondary outcomes included clinical features, such as KD phenotype, organ involvement, shock, intensive care unit admission, and coronary artery lesions. Results: Among 398 patients registered, central review identified 129 MIS-C cases (mean age: 8·8 ± 3·7 years). The overall incidence rate was estimated to be 1·5 per 100,000 COVID-19 cases, exhibiting a decline as the COVID-19 pandemic progressed, from 12·3 cases (Pre-Delta) to 1·3 cases (Omicron); 80% of MIS-C cases occurred during the Omicron variant predominant period, and 72% of children with MIS-C met the KD criteria. Cardiovascular (88%) and gastrointestinal (90%) involvement were frequent. In Japan, MIS-C cases showed comparatively less severe clinical features, with shock in 29% and admission to the intensive care unit in 12% of cases. Coronary artery lesions were identified in 15 cases (11·6%), irrespective of the presence of shock. No fatalities were reported. Conclusion: The incidence of MIS-C was low in Japan. The clinical features distinctively exhibited a more KD-like phenotype, with less severe clinical features. [ABSTRACT FROM AUTHOR]

Multisystem Inflammatory Syndrome in children (MIS-C) is a rare and novel pediatric complication linked to COVID-19 exposure, which was first identified in April 2020. A small n, Sequential, Multiple Assignment, Randomized Trial (snSMART) was applied to the Multisystem Inflammatory Syndrome Therapies in Children Comparative Effectiveness Study (MISTIC) to efficiently evaluate multiple competing treatments. In the MISTIC snSMART study, participants are randomized to one of three interventions (steroids, infliximab or anakinra), and potentially re-randomized to the remaining two treatments depending on their response to the first randomized treatment. However, given the novelty and urgency of the MIS-C disease, in addition to patient welfare concerns, treatments were not always administered sequentially, but allowed to be administered concurrently if deemed medically necessary. We propose a pragmatic modification to the original snSMART design to address the analysis of concurrent versus sequential treatments in the MISTIC study. A modified Bayesian joint stage model is developed that can distinguish a concurrent treatment effect from a sequential treatment effect. A simulation study is conducted to demonstrate the improved accuracy and efficiency of the primary aim to estimate the first stage treatments' response rates and the secondary aim to estimate the combined first and second stage treatments' responses in the proposed model compared to the standard snSMART Bayesian joint stage model. We observed that the modified model has improved efficiency in terms of bias and rMSE under large sample size settings. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions. [ABSTRACT FROM AUTHOR]

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Severe COVID-19 and MIS-C are rare but serious outcomes associated with SARS-CoV-2 infection. The onset of MIS-C often involves the gastrointestinal system, suggesting a potential connection with gut microbiota. This study aims to compare the gut microbiota of children with severe COVID-19 and those with MIS-C using various biomolecular approaches. Gut microbiota composition and specific microbial modulations were analyzed using fecal samples collected at hospital admission. The study included hospitalized patients (mean age 6 ± 5 years) diagnosed with severe COVID-19 (37 patients) or MIS-C (37 patients). Microbial differences were assessed using both NGS and qRT-PCR methodologies. In 75% of cases, pharmacological treatments included antibiotics and corticosteroids, which influenced the microbiota composition. Early age was found to have the most significant impact on microbiota diversity. Significant differences in alpha and beta diversity were observed between COVID-19 and MIS-C patients, particularly concerning low-abundance species. Levels of Bacteroides spp., Bifidobacterium spp., and Akkermansia muciniphila were comparable between groups, while an increased activity of Bifidobacterium spp. was noted in children with positive fecal samples (p = 0.019). An in-depth evaluation of lesser-known gut species may be key to reducing the risk of severe outcomes and developing microbiota-based biomarkers for the early diagnosis of MIS-C. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), which is now known to be caused by severe acute respiratory syndrome coronavirus 2, has been a public health threat since early 2020 and has affected millions of people worldwide. Many studies have now shown that this virus exhibits a milder infection in children compared to adults. Acute COVID-19 infection, multisystem inflammatory syndrome in children (MIS-C), and long COVID have been recently well-established in the pediatric population with a myriad of systemic manifestations. This section of the review will focus on the following systems—neurology, psychiatry, endocrinology, hematology, and oncology—under three broad lenses, such as acute COVID-19, MIS-C, and long COVID. [Pediatr Ann. 2025;54(1):e40–e44.] [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on nuclear factor–κB signaling. Nine rare, potentially deleterious variants were found in 8 of 21 patients, located in the IL17RC , IFNA10 , or NLRP12 gene. Unlike the wild type NLRP12 protein, which inhibits nuclear factor–κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion The severity of COVID‐19 is influenced by uncontrolled hyper‐inflammatory response with excessive release of many cytokines and chemokines. The understanding of the temporal change in the cytokine levels that underlies the diverse clinical presentations of COVID‐19 can help in the prediction of the disease outcome and in the design of proper treatment strategies.Data were collected from children (<18 years old) hospitalised with severe COVID‐19 or severe MIS‐C who were compared to a group of healthy control children. Patient demographics, clinical, laboratory data and cytokines profiles were evaluated. Blood samples were collected within 24 h of admission for all enrolled children and on Day 14.Twenty‐five children with severe COVID‐19 and 23 cases with severe MIS‐C were included in the study. The biochemical and inflammatory markers tend to be elevated in MIS‐C group. There was a significant difference between studied cases and the control group in the following cytokines: G‐CSF, IL‐10, HMGB1, TNF‐α, IL‐6, IL‐8 and INF‐gamma (P < 0.05). While there was a significant difference between severe COVID‐19 and MIS‐C groups in the following cytokines at Day 1 of admission; IL‐10, IL‐6, IL‐8 and INF‐gamma; while at Day 14, there was a significant difference only for G‐CSF, IL‐10 and IL‐6, all other cytokines were comparable.Our study underpinned patterns of cytokine response in severe COVID‐19 and MIS‐C. There is a significant upregulation in pro‐inflammatory cytokines (mainly G‐CSF, IL‐10, HMGB1, TNF‐α, IL‐6, IL‐8 and INF‐gamma). These biomarkers that could imply on the severity rating and treatment strategies, should be preferentially assessed in SARS‐CoV‐2 associated immunological events. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in children (MIS-C) is a relatively rare complication of Covid-19 infection occurring in children and adolescents. Some of its clinical presentations overlap with those of Kawasaki disease (KD). We report the case of a six-year-old girl who presented with a six-day history of fever, bilateral conjunctivitis, oral mucosal changes, generalised body rash and cervical lymphadenopathy, all of which are common presentations for both MIS-C and KD. There was, however, a history of Covid-19 infection one month prior, and her Covid-19 antibodies were positive. Laboratory investigations revealed elevated inflammatory markers, including C-reactive protein, ferritin, procalcitonin and interleukin-6, as well as an elevated troponin level. These findings, in combination with the clinical history, were consistent with MIS-C. Intravenous immunoglobulin and corticosteroids were administered, leading to clinical improvement. This case highlights the common and divergent features of MIS-C and KD and the importance of recognising these features for effective treatment and improved outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to assess if body mass index (BMI) affects the pace of cardiac muscle recovery in children after Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2/COVID-19 (PIMS-TS). Methods: A prospective single-center study enrolled consecutive children hospitalized with PIMS-TS between October 2020 and February 2022 and followed up after 6 weeks and 6 months. In all children, three-dimensional echocardiography and global longitudinal strain were used to assess ventricular function and the results were analyzed according to patients' BMI status. Results: This study enrolled 170 patients aged 1–17 years, median 8.5 ± 4.43 years. Children with normal BMI (>5th and <85th percentile; n = 115) accounted for 67.65%, overweight and obese children (>85th percentile; n = 40) accounted for 23.53% and underweight children (<5th percentile; n = 15) accounted for 8.82% of the participants. In all patients, the means of left and right ventricular ejection fractions (LVEF and RVEF) in 3D-ECHO and average GLS were within normal limits at discharge and during follow-up. However, in children with normal weight, the function of the left ventricle improved between 6 weeks and 6 months according to both GLS and LVEF (respectively: LV GLS −20.19 ± 3.88% and −23.17 ± 2.58, p < 0.05; LVEF 60.68 ± 2.64% and 63.58 ± 2.49%, p < 0.05), while no significant improvement was observed in underweight, overweight and obese children. In patients with BMI > 85th percentile, the mean of left ventricular GLS after 6 weeks, although in the normal range, was significantly lower than in underweight children (respectively: −20.09 ± 2.5% and −23.55 ± 3.55%, p = 0.002), whereas left ventricle function assessed with 3D-ECHO showed no significant difference in both groups at that time (BMI > 85th percentile LVEF 61.15 ± 3.21%, BMI < 5th percentile LVEF 61.30 ± 2.71%, p = 0.36). During the study period, right ventricular function remained within normal limits and no significant differences according to both GLS and RVEF were reported between weight status groups. However, further significant right ventricular function improvement between 6 weeks and 6 months was observed in children with normal weight according to GLS (respectively: −22.6 ± 4.51% and −24.16 ± 2.97%, p = 0.02), while RVEF in 3D-ECHO remained unchanged (respectively: 64.01 ± 3.61% and 64.53 ± 3.15%, p = 0.63). In groups of underweight, overweight and obese children, no significant changes between 6 weeks and 6 months were observed (BMI < 5th percentile RVEF at 6 weeks 66.20 ± 2.86% and BMI < 5th percentile RVEF at 6 months 65.20 ± 2.28%, p = 0.58; BMI > 85th percentile RVEF at 6 weeks 63.44 ± 3.00% and BMI > 85th percentile RVEF at 6 months 64.11 ± 2.52%, p = 0.58). Conclusions: Left and right ventricular function stayed within normal limits 6 weeks after PIMS-TS regardless of patients' BMI. Left and right ventricular function improved further between 6 weeks and 6 months after acute disease in the group of children with normal BMI. GLS is a sensitive tool for its assessment. Lower ventricular GLS in children with BMI > 85th percentile may indicate poorer left ventricular performance. Children with normal BMI may present with a more advantageous cardiac recovery pace after PIMS-TS. [ABSTRACT FROM AUTHOR]

Background: Severe clinical manifestations of multisystem inflammatory syndrome in children (MIS-C) are associated with the dysregulation of immune response following SARS-CoV-2 infection. Therefore, we analyzed the levels of 10 selected cytokines at admission to estimate disease severity and to predict the length of hospitalization. In remission samples, these mediators were followed after intravenous immunoglobulin (IVIG) treatment before discharge. Methods: Thirty-five MIS-C patients at the age of 8.4 ± 4.1 years and 11 clinical controls were included. Acute MIS-C patients were divided into two severity subgroups based on their clinical score determined by the WHO criteria. Serum concentrations of IFN-γ, IL-1α, IL-1RA, IL-8, IL-10, IL-17A, IL-18, IP-10, MCP-1, and TNF-α were measured by MILLIPLEX® Human Cytokine/Chemokine panel, while ACE2 activity was determined by a fluorescent kinetic assay. These results were correlated with routinely determined laboratory parameters and clinical characteristics. Results: MIS-C patients demonstrated significantly elevated baseline levels of most of these cytokines compared to controls. Even higher concentrations of IL-18, TNF-α and ferritin with reduced lymphocyte count were found in severe subjects with elevated clinical scores of 4–5 compared to moderate cases with a clinical score of 1–3. Furthermore, the development of cardiovascular dysfunction and prolonged hospitalization (≥8 days) were related to augmented ACE2 and IL-6 levels. IL-18, IL-1RA, IL-10 and TNF-α were diminished in response to IVIG treatment in remission samples. Finally, pre-treatment IL-18 (≥516.8 pg/mL) and TNF-α (≥74.2 pg/mL) effectively differentiated disease severity in MIS-C with AUC values of 0.770 and 0.750, respectively. Conclusions: IL-18 and TNF-α have a prognostic value in disease severity at admission and are capable of monitoring the efficacy of IVIG treatment in MIS-C. [ABSTRACT FROM AUTHOR]

A hydropneumothorax is an uncommon complication of pneumonia, particularly in pediatric patients, and typically arises secondary to conditions such as malignancies, esophageal-pleural fistula, thoracic trauma, or thoracocentesis. While pneumothorax is rarely reported in adults with COVID-19 and is even less common in children, isolated cases have been noted in those with Multisystem Inflammatory Syndrome in Children (MIS-C). A recent alert has also been issued about increased Group A Streptococcus (GAS) infections in Europe. Against this background, the primary aim of this case report is to describe a rare and severe complication of pneumonia in a previously healthy child with MIS-C and a positive throat culture for GAS. [ABSTRACT FROM AUTHOR]

Studies on the severity in multisystem inflammatory syndrome in children (MIS-C) show heterogeneous results and may not reflect a global perspective. This systematic review aims to estimate the frequency of in-hospital unfavorable outcomes in patients with MIS-C over the 3 years since the onset of the SARS-CoV-2 pandemic. A systematic search was conducted in Medline, Scopus, Embase, Cochrane, Web of Science, Scielo, and preprint repositories until December 15, 2022. Study selection and data extraction were evaluated independently. The primary outcomes were intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and death. Additionally, we evaluated cardiovascular-related outcomes. We performed a random-effects model meta-analysis and assessed the certainty of the evidence. Fifty-seven studies (n = 13 254) were included. The frequency of ICU admission was 44.7% (95% CI 38.8–50.7), 11.9% for IMV (95% CI 9.6–14.4), and 2.0% for death (95% CI 1.3–3.0). The requirement of vasoactive/inotropic drugs was 40.1% (95% CI 35.9–44.4), 7.9% for coronary aneurysm (95% CI 4.1–12.7), 30.7% for decreased left ventricle ejection fraction (LVEF) (95% CI 26.3–35.4), and 29.7% for myocarditis (95% CI 18.4–42.4). We assess the included evidence as being of very low certainty. Finally, excess COVID-19 mortality by country and the diagnostic criteria for MIS-C (CDC compared to WHO) were associated with a higher frequency of ICU admissions. The year of study conduction (2022 compared to 2020) was associated with a lower frequency of IMV. Conclusion: The frequency of in-hospital unfavorable outcomes in patients with MIS-C was high. Well-designed studies are needed to explore other heterogeneity sources. Protocol registration: CRD42021284878. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) is a serious post-infectious condition linked to SARS-CoV-2. Studies on the severity of MIS-C show heterogeneous results. These findings may not be representative of the reality in other regions, making it challenging to draw generalizable conclusions. What is New: • Over the 3 years since the onset of the SARS-CoV-2 pandemic, our systematic review has shown that the frequency of in-hospital unfavorable outcomes in patients with MIS-C is high, with a very low certainty of the evidence. Our results reflect the reality from a global perspective, across different countries with varying income levels. • The main sources of heterogeneity in the frequency of severe outcomes could be explained by the excess mortality due to COVID-19 in each country, the type of diagnostic criteria for MIS-C, and the year the study was conducted. [ABSTRACT FROM AUTHOR]

Background: Multilayer strain magnetic resonance imaging (MRI) analysis offers detailed insights into myocardial mechanics and cardiac function by assessing different layers of the heart muscle, enabling a comprehensive understanding of cardiac involvement. Objective: This study aims to explore cardiac strain differences between patients with multisystem inflammatory syndrome and a control group at medium-term follow-up, utilizing a layer-specific cardiac magnetic resonance imaging (CMR) approach. Materials and methods: In this retrospective study, patients with multisystem inflammatory syndrome in children (MIS-C) and a group of controls who had undergone cardiac magnetic resonance (CMR) imaging were selected and included. CMR was performed 30 days after discharge (range 34–341 days) for MIS-C patients. TrufiStrain research prototype software (Siemens Healthineers AG, Erlangen, Germany) was used for automated myocardial segmentation and strain calculation, to measure radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) at the epicardial, mid-wall, and endocardial levels. Statistical analysis included Shapiro–Wilk tests, Student t-tests, and Mann–Whitney U tests, ANOVA, and regression analysis, maintaining a significance level of α = 0.05. Results: The study cohort consisted of 32 MIS-C patients (≤ 18 years; 14 females) and 64 control participants (≤ 18 years; 24 females). Median interval to CMR post diagnosis was 142 days (range 34–341) with normal CMR findings for all patients. The mean age of the two groups was similar (MIS-C: 14.2 years; controls: 14.1 years, P = 0.49). There were no significant differences in height (MIS-C: 164.7 cm; controls: 163.9 cm, P = 0.84), weight (MIS-C: 68.2 kg; controls: 59.4 kg, P = 0.11), or body surface area (MIS-C: 1.7 m2; controls: 1.7 m2, P = 0.41). Global strain measurements showed no significant differences between the groups (global LS MIS-C patients − 16.2% vs − 15.7% in controls (P = 0.23); global RS 27.8% in MIS-C patients vs 29.5% in controls (P = 0.35); and global CS − 16.7% in MIS-C patients vs − 16.8% in controls (P = 0.92)). Similarly, layer-specific strain analysis across the endocardial (LS values of − 17.7% vs − 16.8% (P = 0.19), RS of 23.1% vs 24.8% (P = 0.25), and CS of − 19.9% vs − 19.9% (P = 0.92)), epicardial (LS − 14.9% vs − 14.5% (P = 0.31), RS of 31.2% vs 33.1% (P = 0.29), and CS of − 14.1% vs − 14.2% (P = 0.75)), and midmyocardial (LS − 16.5% vs − 16.3% (P = 0.18), RS 29.3% vs 31.8% (P = 0.31), and CS − 17.0% vs − 17.2% (P = 0.95)) levels revealed no significant disparities. The only notable finding was the reduced apical radial strain in MIS-C patients compared to controls (global RS MIS-C 12.4% vs 17.4% in controls, P = 0.03; endocardium RS MIS-C 4.9% vs 10.31% in controls, P = 0.01; epicardial RS MIS-C 17.7% vs 22.6% in controls, P = 0.02; and midmyocardium RS MIS-C 12.5% vs 17.9% in controls, P = 0.02). Conclusion: This study demonstrates that MIS-C does not significantly impact global or layer-specific myocardial strain values, as assessed by CMR, compared to a control group. The lower apical radial strain in MIS-C patients indicates a potential localized myocardial involvement. [ABSTRACT FROM AUTHOR]

Background: Macrophage activation syndrome (MAS) can be regarded as a key factor determining the severity of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C), and often requires treatment in the intensive care unit (ICU) to avoid life-threatening complications. No reputable specific criteria for the diagnosis of MAS in MIS-C patients have yet been identified, and criteria currently used for the diagnosis of hemophagocytic syndromes, such as HLH-2004, MAS-2005, and MAS-2016, are not sufficient for MAS in MIS-C. Our goal in this study was to work out the criteria for the early diagnosis of MAS in MIS-C. Methods: One hundred and sixty-six (166) patients with MIS-C were assessed retrospectively. The two most experienced experts independently identified patients with MAS. The patients were divided into three cohorts: MAS (n = 19), without MAS (n = 78), and probable MAS (n = 67). The latter included patients diagnosed with MAS by only one expert, and it was excluded from the analysis. Results: The age of patients with MAS was much higher, and they more frequently had edematous syndrome, hypotension and/or shock, splenomegaly, and CNS involvement. In their blood tests, thrombocytopenia, hypoalbuminemia, and hypertriglyceridemia occurred more often. The level of biomarkers of inflammation, such as ferritin, CRP, troponin, AST, and ALT, was also higher in this group. Increased fibrinogen and D-dimer were also found, demonstrating hypercoagulation in the MAS-MIS-C group. We chose 21 continuous and categorical variables with statistical significance, out of which 2—ferritin > 469 μg/L or platelets < 114 × 109/L—allowed us to discriminate MAS patients. Conclusions: Ferritin > 469 μg/L or platelets < 114 × 109/L can be regarded as key signs to differentiate MAS in MIS-C patients with a sensitivity of 100% and specificity of 94.9%, and they can be used along with other diagnostic methods. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) originated in Wuhan, China, in late 2019. Within a span of a few months, it was deemed a global pandemic by the World Health Organization. It was first thought to affect the adult population, but soon after, cases of COVID-19 in children started emerging. As more and more pediatric cases started unveiling, an entity called multisystem inflammatory syndrome in children (MIS-C) that replicated Kawasaki disease was established. More recently, it has been noted that children have persistent symptoms for weeks or months after acute COVID-19 infection, and the term coined for these symptoms is "long COVID." This section of the review will summarize the respiratory, cardiovascular, dermatological, and gastroenterological manifestations noted in infants in three broad categories: acute COVID, MIS-C, and long COVID. [Pediatr Ann. 2024;53(12):e473–e477.] [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the range of clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C) with COVID-19 in a tertiary children's hospital in Northwest Iran during 2020–2022. According to the CDC guidelines, this cross-sectional study included 300 pediatric patients diagnosed with MIS-C. Data were collected retrospectively from medical records, focusing on symptoms, organ involvement, laboratory findings, and outcomes. Statistical analysis was performed using SPSS software, with significance set at p-values <0.05. The study population had a median age of 3 years, with a slight male predominance (57.3%). The most affected systems in MIS-C disease were hematological (87%), gastrointestinal (85%), and respiratory (67%). Laboratory analysis highlighted elevated inflammatory markers such as D-dimer (83.3%), ferritin (71.4%), and CRP (49.7%). Abnormal urinalysis was observed in 151 patients (50.3%), with glucosuria in 83 cases (27.7%) and proteinuria in 29 cases (9.7%). The study found a significant correlation between cardiovascular issues and elevated blood platelets, ESR, CRP, and troponin levels (P ≤ 0.01) but not with ferritin, albumin, or D-dimer levels. Also, the examination of disease outcomes in this study revealed that 81.7% of MIS-C patients were isolated during their hospital stay, 18.3% needed ICU care, and 1% died in hospital. We have presented an experience with distinct clinical and laboratory manifestations in MIS-C. Given the lower median age in this study compared to previous studies, reporting clinical and laboratory manifestations of MIS-C in pediatrics with a younger age is valuable for the diagnosis and treatment course. Some laboratory factors were risk factors for cardiovascular involvement, and consequently, echocardiography is recommended in MIS-C patients with these laboratory indications. Given the lack of a specific diagnostic test for this emerging disease, studies focusing on investigating clinical symptoms and findings are valuable. [ABSTRACT FROM AUTHOR]

Background/Objectives: To investigate if the severity and presentation of multisystem inflammatory syndrome in children (MIS-C) vary between different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Methods: This retrospective study included 59 patients aged 0–18 years, diagnosed with COVID-19 and MIS-C, treated and monitored over a one-year period after discharge from hospital. The patients were grouped according to the predominant SARS-CoV-2 variant. The predominant variant of SARS-CoV-2 was assumed by the date of hospitalization. The following patient data were collected: demographic data (age, sex), information on comorbidities, body mass index, clinical data (fever and duration of febrile periods, symptoms of Kawasaki-like phenotypes, and presence of respiratory, cardiovascular, gastrointestinal, neurological and other symptoms), and laboratory and imaging findings. Results: In total, 24 (41%), 19 (32%), and 15 (25%) patients were diagnosed with MIS-C during the Alpha, Delta, and Omicron periods, respectively (63.8% were males; 36.2% were females). Comorbidities were present in 49% of patients. Respiratory symptoms were the most common during the Delta period (73%, p = 0.028). There was no statistically significant difference in the occurrence of other symptoms, laboratory findings, treatment, complications, and long-term outcomes between groups. Conclusions: No significant correlation was found between hospitalization date (used to estimate COVID-19 variant) and presentation/severity of MIS-C. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 infection can lead to a potentially life-threatening condition known as SARS-CoV-2-associated multisystem inflammatory syndrome in children (MIS-C), which differs from the severe lung disease and thrombotic complications commonly seen in adults. Recently, similar cases have been identified in adults, characterized by a clinical multisystem inflammatory syndrome referred to as MIS-A, which can emerge as a late and severe complication of SARS-CoV-2 infection. Case Presentation: We report two cases of MIS-A that were recently admitted to our hospital. Both patients developed a severe multisystem inflammatory syndrome despite experiencing only mild SARS-CoV-2 infection. Key clinical features in both cases included significant systemic inflammation, prominent cardiac involvement, and thrombocytopenia. Prior SARS-CoV-2 infection was confirmed through serological testing. Treatment protocols for MIS-C, including steroids and immunoglobulins, proved effective for both patients. Conclusions: Clinicians should remain vigilant for MIS-A in the context of ongoing SARS-CoV-2 infection worldwide. This infection, even when presenting with mild or no symptoms, can progress to a life-threatening hyperinflammatory syndrome with cardiac implications if not promptly recognized and treated. [ABSTRACT FROM AUTHOR]

Although most children are spared from developing complications from SARS-CoV-2 infection, some may suffer consequences including Long Covid and multisystem inflammatory syndrome in children (MIS-C). Although the occurrence of these conditions has decreased over time, they can still occur, and recognition of symptoms and prompt diagnosis is imperative for early intervention. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome of children (MIS-C) is a clinical picture that entered the medical nomenclature after the coronavirus disease 2019 pandemic. Although it primarily affects older children, there have been a limited number of cases reported during the neonatal period. Herein we present a patient, a late preterm infant, with severe MIS-C-related cerebral sinus venous thrombosis who was successfully treated with therapeutic plasma exchange. Practitioners can consider therapeutic plasma exchange as a safe and effective option for the treatment of critically ill MIS-C cases. [ABSTRACT FROM AUTHOR]

Background: Background: This study aimed to describe Correlation between Kawasaki disease & MIS-C in Indira Gandhi Medical College, Shimla. Material & Methods: We conducted a cross-sectional study for MIS-C from January to July 2021, in the pediatric ward of Indira Gandhi Medical College Shimla in Himachal Pradesh, in Western Himalayas. All children admitted with a diagnosis of MIS-C were included in the study. Data regarding sociodemographic factors and Kawasaki cases were extracted and analyzed using Epi Info V7 software. Results: In the present study, a total of 31 children diagnosed & admitted as a case of MIS-C were included. Mean age of these patients was 7.12±4.78 years. Among the total 16(51.6%) were males while 15(48.4%) were females. Of, 31 cases of MIS-C, 5 children presented KD. All of them were males. 3 children were less than5 years, while 2 were 6-10 years old. Echo was normal in 4 cases and 1 had low ejection fraction. IVIG was given to all, while LMWH was given to one child. Methylprednisolone in low doses to 4 children, while in 1recieved high dose. Aspirin was given to 4 patients. Oxygen therapy in 3 patients, ventilatory support was given to one child, while inotropic support was given to 2 patients. All 5 patients were discharged after full recovery. Conclusion: Given the frequent overlap of clinical manifestations between MIS-C and those of Kawasaki disease, the majority of patients with hyperinflammatory syndrome have generally been treated with the standard therapeutic protocols used in Kawasaki disease. [ABSTRACT FROM AUTHOR]

Background/aim: Differentiating multisystem inflammatory syndrome in children (MIS-C) from adenovirus infection (AI) can be challenging due to similar clinical and laboratory findings. This study aimed to identify distinguishing characteristics and develop a scoring system to facilitate accurate diagnosis. Materials and methods: A comprehensive review of medical records was undertaken for 108 MIS-C patients and 259 patients with confirmed AI. A comparison of laboratory data and clinical findings was conducted across the patient groups using appropriate statistical tests. Results: The MIS-C patients were significantly older than the AI patients (p < 0.001). Diarrhea, rash, abdominal pain, vomiting, nonexudative conjunctivitis, lymphadenopathy tachycardia, bradycardia, hypotension, hypoxia seizures, agitation, headache, and altered consciousness symptoms were more frequently associated with MIS-C (p < 0.001), while cough and runny nose were significantly more common in AI (p < 0.001). Lymphopenia and thrombocytopenia were more prevalent in the MIS-C patients (p < 0.001). AI and MIS-C were scored by giving one point each to the parameters that created the difference. For AI, being =60 months of age, the presence of cough, runny nose and absence of diarrhea, rash, abdominal pain, vomiting, nonexudative conjunctivitis, lymphadenopathy, tachycardia, bradycardia, hypotension, hypoxia seizures, agitation, headache, and altered consciousness, lymphopenia, thrombocytopenia, and C-reactive protein value <124.5 mg/L were determined as each parameter plus one point. A total score above 14 could predict AI with a high degree of accuracy, with sensitivity at around 97.5% and specificity at 92.6%. Conclusion: The proposed inpatient scoring system, when used in conjunction with polymerase chain reaction testing, may improve the early differentiation of AI and MIS-C. This approach could help reduce unnecessary testing and optimize resource allocation. Further research with larger samples should investigate this novel scoring system to establish its reliability and generalizability. [ABSTRACT FROM AUTHOR]

Background Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines. Methods We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay. Results Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups. Conclusions We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome is a severe complication of SARS-CoV-2 infection in children (MIS-C). To date, data on long-term sequelae mainly concern cardiac outcomes. All ≤ 18 year olds consecutively admitted to the Buzzi Children's Hospital with a diagnosis of MIS-C between October 1, 2020, and May 31, 2022, were followed up for up to 12 months by a dedicated multidisciplinary team. They underwent laboratory tests, multi-organ clinical and instrumental assessments, and psychosocial evaluation. 56/62 patients, 40 M, mean age 8.7 years (95% CI 7.7, 9.7), completed the follow-up. Cardiological, gastroenterological, pneumological, and neurological evaluations, including IQ and EEG, were normal. Alterations of HOMA-IR index and/or TyG index, observed in almost all patients during hospitalisation, persisted in about a third of the population at 12 months. At 6 and 12 months respectively, impairment of adaptive functions was observed in 38/56 patients (67.9%) and 25/56 (44.6%), emotional and behavioural problems in 10/56 (17.9%) and 9/56 (16.1%), and decline in QoL in 14/56 (25.0%) and 9/56 (16.1%). Psychosocial well-being impairment was significantly more frequent in the subgroup with persistent glycometabolic dysfunction at 12 months (75% vs. 40.9% p < 0.001). Conlusion: The mechanisms that might explain the long-term persistence of both metabolic alterations and neuro-behavioural outcomes and their possible relationship are far from being clarified. Our study points out to the potential long-term effects of pandemics and to the importance of a multidisciplinary follow-up to detect potential negative sequelae in different areas of health, both physical and psychosocial. What is known: • Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. • Few data exist on the medium- and long-term outcomes of MIS-C, mostly focused on cardiac involvement. Emerging evidence shows neurological and psychological sequelae at mid- and long-term follow-up. What is new: • This study reveals that MIS-C may lead to long-term glycometabolic dysfunctions joined to impairment in the realm of general well-being and decline in quality of life, in a subgroup of children. • This study highlights the importance of a long-term multidisciplinary follow-up of children hospitalised with MIS-C, in order to detect the potential long-term sequelae in different areas of health, both physical and psychosocial well-being. [ABSTRACT FROM AUTHOR]

This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD. [ABSTRACT FROM AUTHOR]

Background and Objectives: Due to its link with the SARS-CoV-2, Multisystem Inflammatory Syndrome in Children (MIS-C) gained global attention as a serious condition that requires hospital care. Our study aimed to present the clinical and laboratory characteristics of MIS-C patients by age group and intensive care unit (ICU) admission status and assess early echocardiographic changes. Materials and Methods: A single-center partly retrospective, partly prospective observational cohort study was performed from December 2020 to June 2024. The study included 42 patients aged between 1 month and 18 years who were diagnosed with MIS-C and gave informed consent. Results: The median age was 6.5 years (IQR 2.0–9.3). The predominant symptoms were cardiovascular (88.1%), mucocutaneous (85.7%) and gastrointestinal (76.2%). Five children (11.9%) developed shock. About two-thirds of patients (66.7%) were admitted to the ICU. Adolescents (≥12 years) were less likely to exhibit mucocutaneous or cardiovascular symptoms and thus less frequently having Kawasaki—like disease symptoms compared with other age groups (<5 years or 5–11 years). Lymphopenia was more common among patients aged 5 years and older. Adolescents had higher procalcitonin (PCT) and a lower estimated glomerular filtration rate. Troponin I and B-type natriuretic peptide (BNP) levels were higher in children aged 5–11 years, while ferritin levels were lower among the youngest (<5 years). Patients treated at the ICU were more likely to have cardiovascular and respiratory symptoms, as well as a history of symptomatic COVID-19, higher C-reactive protein (CRP), PCT, BNP and lower albumin levels. Echocardiographic abnormalities were found in 71.4% of cases. During hospitalization, left ventricular ejection fraction values increased significantly (p < 0.001) over 12 (IQR 9.0–14.0) days. Conclusions: Symptoms and laboratory markers of MIS-C vary according to age. Higher CRP, PCT, BNP and hypoalbuminemia are predictors of MIS-C severity. Cardiovascular involvement is common and might be severe, but rapid resolution is encouraging. [ABSTRACT FROM AUTHOR]

Background/objectives: The immunological pathways that cause Multisystem Inflammatory Syndrome after SARS-CoV-2 infection in children (MIS-C) remain under investigation. Methods: The aim of this study was to prospectively compare the T-cell cytokine expression profile in unvaccinated children with acute MIS-C (MISC_A) before immunosuppression, convalescent MIS-C (one month after syndrome onset, MISC_C), convalescent COVID-19 (one month after hospitalization), and in healthy, unvaccinated controls. The intracellular expression of IL-4, IL-2, IL-17, IFNγ, TNF-α and Granzyme B, and the post SARS-CoV-2-Spike antigenic mix stimulation of T-cell subsets was analyzed by 13-color flow cytometry. Results: Twenty children with a median age (IQR) of 11.5 (7.25–14) years were included in the study. From the comparison of the flow cytometry analysis of the 14 markers of MISC_A with the other three groups (MISC_C, post-COVID-19 and controls), significant differences were identified as follows: 1. CD4+IL-17+/million CD3+: 293.0(256.4–870.9) vs. 50.7(8.4–140.5); p-value: 0.03, vs. 96.7(89.2–135.4); p-value: 0.03 and vs. 8.7(0.0–82.4); p-value: 0.03, respectively; 2. CD8+IL-17+/million CD3+: 335.2(225.8–429.9) vs. 78.0(31.9–128.9) vs. 84.1(0.0–204.6) vs. 33.2(0.0–114.6); p-value: 0.05, respectively; 3. CD8+IFNγ+/million CD3+: 162.2(91.6–273.4) vs. 41.5(0.0–77.4); p-value: 0.03 vs. 30.3(0.0–92.8); p-value: 0.08, respectively. Conclusions: In children presenting with MIS-C one month after COVID-19 infection, T cells were found to be polarized towards IL-17 and IFNγ production compared to those with uncomplicated convalescent COVID-19, a finding that could provide possible immunological biomarkers for MIS-C detection. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has significant effects on organ function, particularly on lung function and iron metabolism. Studies have shown increased levels of ferritin, an iron storage protein, in COVID-19 patients, indicating potential changes in iron utilization. Research has focused primarily on adults, with limited studies on paediatric patients and a lack of comparisons with MIS-C patients. This study aimed to assess iron status in paediatric COVID-19 patients using traditional and new biomarkers, soluble transferrin receptors (sTfR) and Reticulocyte hemoglobin equivalent (RET-He), to improve diagnosis and prognosis. Additionally, we sought to compare iron status between acute COVID-19 patients and MIS-C patients and evaluate the relationships among iron dysmetabolism, disease severity, and prognosis in paediatric patients. The study also involved monitoring iron status during and after infection to understand its impact on patient severity and prognosis. Methods: A cohort study involving 49 patients aged 1 month to 18 years was conducted at the isolation department of Mansoura University Children's Hospital. The study included 36 patients with acute COVID-19 and 13 with multisystem inflammatory syndrome of childhood (MIS-C). Diagnosis was based on PCR from a deep nasopharyngeal swab or a positive antibody test. Follow-up of survivors was conducted 3 months after recovery. Blood samples were obtained during infection and at follow-up for CBC, Ret-He, iron kinetics, and sTfR analyses. Results: Significant iron deficiency anaemia was observed in all patients during infection, with improvement after 3 months of recovery in survivors. The improvement was more obvious in MIS-C patients, with Hb and iron kinetics not significantly affected by disease severity. The STfR was significantly lower in nonsurvivors than in survivors. The ROC curve showed that a baseline sTfR ≤ 18 nmol/L was a statistically significant difference between nonsurvivors and survivors (area under the curve (AUC) = 0.810, p <.001), with 66.7% sensitivity and 82.5% specificity. Regression analysis revealed that patients with baseline sTfRs ≤ 18 nmol/L were 5.9 times more susceptible to death. Conclusion: This study revealed that COVID-19 in children caused iron deficiency anaemia, which improved within 3 months after recovery. Haemoglobin and sTfRs were identified as reliable indicators of IDA in these patients, unlike iron kinetics and RET-He. [ABSTRACT FROM AUTHOR]

Objective: Multisystem inflammatory syndrome in children (MIS-C) is a critical childhood disease that is associated with coronavirus disease (COVID-19). We aimed to describe the clinical, laboratory, and echocardiographic characteristics and outcome of critical MIS-C cases in Egyptian children during the first wave of the COVID-19 pandemic. Design: A retrospective, observational study. Setting: A single-center tertiary pediatric intensive care unit (PICU).In Ain Shams university hospitals Cairo Egypt Methods: Children admitted to the PICU diagnosed with severe MIS-C as per the Centers for Disease Control's definition from June 23, 2020, to August 22, 2020, were included. Results: The patient's mean age was 7.45 (interquartile range [IQR], 4.23) years, and the cause of PICU admission was hypotension and shock. All patients had a fever for 4.8 (IQR, 2.5) days before shock developed. Overall, 68% had a gastrointestinal manifestation, and 55.6% had a rash. Thirty-five of 45 patients had ≥ 4 elevated inflammatory markers. The cardiac troponin I level was elevated in 35 of 45 patients. The most common cardiac condition was valvulitis (tricuspid regurgitation, 29/45; mitral valve regurgitation, 28/45; pulmonary valve regurgitation, 5/45; atrial valve regurgitation, 4/45). Twenty-one patients had an impaired ejection fraction < 50%, and 17 patients had coronary dilatation. Six patients had pericardial effusion, 1 patient had dilated pulmonary arteries, and 6 patients (13.3%) died of their associated comorbidities. The mean PICU length of stay among patients with no associated comorbidities was 7 days. Conclusions: Critical cases of MIS-C had a spectrum of different cardiac conditions, with valvulitis being the most common one. The worst outcome occurred in patients with comorbidities and infants. [ABSTRACT FROM AUTHOR]

The article "We Can Be Heroes: Identification, Superheroes, and the Visual Communication of Agency in Online Children's Books about COVID-19" delves into how children's picture books during the pandemic use superheroes as metaphors to empower children to adopt health behaviors like wearing masks and washing hands. It emphasizes the importance of visual and textual metaphors in shaping children's understanding of illness and health, while also discussing the limitations and risks of using such metaphors. The text underscores the significance of community cooperation in combating the virus and stresses the need for clear communication about children's agency in addressing public health issues. The document offers a range of resources on health communication, including online children's books about COVID-19 and discussions on illness as metaphor and the ethics of metaphor in healthcare, catering to researchers and readers interested in health communication and related fields. [Extracted from the article]

Background: Multiple reports have described myopericarditis following mRNA COVID-19 vaccination. However, data on the persistence of subclinical myocardial injury assessed by left ventricular (LV) longitudinal strain (LVLS) is limited. Objectives: Our aim was to assess LV function longitudinally in our cohort of COVID-19 vaccine-related myopericarditis using ejection fraction (EF), fractional shortening (FS), LVLS, and diastolic parameters. Methods: Retrospective, single-center review of demographic, laboratory, and management data was performed on 20 patients meeting diagnostic criteria for myopericarditis after mRNA COVID-19 vaccination. Echocardiographic images were obtained on initial presentation (time 0), at a median of 12 days (7.5, 18.5; time 1), and at a median of 44 days (29.5, 83.5; time 2). FS was calculated by M-mode, EF by 5/6 area-length methods, LVLS by utilization of TOMTEC software, and diastolic function by tissue Doppler. All parameters were compared across pairs of these time points using Wilcoxon signed-rank test. Results: Our cohort consisted predominantly of adolescent males (85%) with mild presentation of myopericarditis. The median EF was 61.6% (54.6, 68.0), 63.8% (60.7, 68.3), 61.4% (60.1, 64.6) at times 0, 1, and 2, respectively. Upon initial presentation, 47% of our cohort had LVLS < -18%. The median LVLS was -18.6% (-16.9, -21.0) at time 0, -21.2% at time 1 (-19.4, -23.5) (p = 0.004) and -20.8% (-18.7, -21.7) at time 2 (p = 0.004, as compared to time 0). Conclusions: Though many of our patients had abnormal strain during acute illness, LVLS improved longitudinally, indicating myocardial recovery. LVLS can be used as marker of subclinical myocardial injury and risk stratification in this population. [ABSTRACT FROM AUTHOR]

Objective: Delirium is an under-recognized problem in critically ill children. Although delirium is common in adults hospitalized with COVID-19, the relationship between pediatric COVID-19 and delirium has not been described. To address this gap, we characterized delirium in critically ill children with different manifestations of COVID-19 and investigated associations among demographic, disease, and treatment factors. We hypothesized that multisystem inflammatory syndrome in children (MIS-C) would be associated with a higher incidence of delirium given its underlying pathophysiology of hyperinflammation. Design: Retrospective, single-center cohort study. Setting: Quaternary-care pediatric intensive care unit (PICU). Patients: Children less than 18 years of age hospitalized in the PICU between March 2020 and March 2023 with either active SARS-CoV-2 infection or serological evidence of prior infection. Measurements and main results: The cohort included 149 PICU hospitalizations among children with evidence of COVID-19. Patients were categorized by reason for PICU admission: 75 (50%) for COVID-19 respiratory disease, 36 (24%) MIS-C, and 38 (26%) any other primary reason with positive COVID-19 testing. Delirium was diagnosed in 43 (29%) patients. Delirium incidence was highest in patients requiring invasive mechanical ventilation (IMV) (56% vs 7.5% in patients who did not require IMV, p <.001). Patients who were exposed to opioids, dexmedetomidine, paralytics or benzodiazepines more frequently experienced delirium compared to those unexposed (p <.001, p <.001, p <.001 and p =.001, respectively). After multivariable adjustment, delirium was associated with IMV (HR 3 [95% CI 1.5–5.7]), female sex (HR 2.4 [1.2–4.7]), and developmental disability (HR 3.4 [95% CI 1–11.1]). There was no association between delirium and reason for PICU hospitalization. Conclusions: Delirium was common among children hospitalized with COVID-19. The overall incidence was much less than has been reported in adults with COVID-19. Delirium reduction efforts should focus on children with developmental disability and minimizing ongoing risks during IMV. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) complications are significant manifestations of COVID-19 and are increasingly being recognized. These complications range from severe acute pancreatitis to colitis, adding complexity to diagnosis and management. A comprehensive database search was conducted using several databases. Our inclusion criteria encompassed studies reporting severe and long-term GI complications of COVID-19. Digestive disorders were categorized into infections, inflammatory conditions, vascular disorders, structural abnormalities, other diagnoses, and undiagnosed conditions. Of the 73 studies that were selected for full-text review, only 24 met our inclusion criteria. The study highlights a broad range of gastrointestinal complications following COVID-19 infection (excluding liver complications, which are examined separately), including inflammatory conditions, such as ulcerative colitis (UC), acute pancreatitis, and multisystem inflammatory syndrome in children (MIS-C). Other GI complications were reported such as vascular disorders, including diverse thrombotic events and structural abnormalities, which ranged from bowel perforations to adhesions. Additionally, undiagnosed conditions like nausea and abdominal pain were prevalent across different studies involving 561 patients. The findings emphasize the substantial impact of COVID-19 on the GI tract. Ongoing research and monitoring are crucial to understanding the long-term effects and developing effective management strategies for these complications. [ABSTRACT FROM AUTHOR]

Background: Characteristics of dermatological manifestations are frequently encountered in pediatric COVID-19, similar to the presentation in multisystem inflammatory syndrome in children (MIS-C), which typically emerges following COVID-19 infection. The rash exhibits considerable diversity and lacks specificity. However, investigations into the dermatological features of COVID-19 in children and MIS-C remain limited. Objective: To investigate cutaneous manifestations in both COVID-19 and MIS-C in children. Materials and Methods: Cross-sectional study between February and August 2022 in hospitalized children with COVID-19 who had cutaneous lesions and all hospitalized children with MIS-C. Results: Forty-six cases of COVID-19 patients with dermatological manifestations were identified among 1,602 COVID-19 patients, constituting 2.9%. Additionally, 35 cases of MIS-C were diagnosed. The majority of COVID-19 patients in the present study exhibited mild symptoms, accounting for 42 cases (91.3%). The median age of COVID-19 patients was 1.8 years, which was significantly lower than that of the MIS-C group, which was 4.3 years, with a statistically significant difference (p=0.024). The most common rash types observed in both groups were urticaria, maculopapular rash, and macular erythema. Other rash types noted in COVID-19 included erythema nodosum, Stevens-Johnson syndrome, erythema multiformelike, vesicles, and livedo reticularis. Among MIS-C patients, 31 cases (88.6%) presented with mucocutaneous manifestations, with 26 cases (74.3%) exhibiting concurrent mucocutaneous involvement. There was no significant difference in the occurrence of cardiac symptoms between the group with mucocutaneous manifestations and/or dermatological symptoms, which was 81.8%, compared to the group without mucocutaneous or dermatological symptoms, which was 100% (p=0.102). Conclusion: The cutaneous manifestations in pediatric COVID-19 and those with MIS-C vary widely and are non-specific. In patients presenting with fever and rash during a COVID-19 outbreak, recognizing these cutaneous symptoms is crucial for prompt diagnosis and treatment especially those who are asymptomatic. Further studies involving COVID-19 patients, both with and without rash, may provide correlation between disease progression and skin manifestation. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare and contrast Kawasaki disease (KD) with multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. Methods: A retrospective analysis of the medical records of patients diagnosed with KD and MIS-C at a single institution from July 2020 to November 2021 was performed. Results: The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. The MIS-C patients were older (p < 0.001) and had prolonged hospitalizations (p = 0.023), elevated neutrophil counts (p < 0.001), C-reactive protein (p < 0.001), procalcitonin (p < 0.001), interleukin-6 (p < 0.014), ferritin (p < 0.001), fibrinogen (p < 0.001), troponin I (p = 0.001), NT-proBNP (p < 0.001), and D-dimer levels (p < 0.001). There were more cases of hypotension (p = 0.024), decreased left ventricular function (p = 0.023), and a greater need for corticosteroids (p < 0.001), enoxaparin (p = 0.045), and therapeutic plasma exchange (p < 0.001). Kawasaki disease patients had a greater incidence of rash (p < 0.001), changes in oral mucosa (p < 0.001), conjunctival injection (p < 0.001), extremity changes (p < 0.001), and cervical lymphadenopathy (p < 0.001). They had a longer duration of fever (p < 0.001), elevated white blood cell count (p < 0.001), platelet count (p < 0.001), and alanine aminotransferase level (p < 0.001). The two groups were similar regarding the hemoglobin levels, erythrocyte sedimentation rates, albumin levels, and the frequency of coronary aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Conclusions: Advanced patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas prolonged fever and classical clinical features of KD favor KD. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) is one of the complications of SARS-CoV-2 infection. This study aims to evaluate the clinical and laboratory characteristics, as well as treatment results, of MIS-C patients who received intravenous immunoglobulin (IVIG) monotherapy. Methods: This retrospective study included patients diagnosed with MIS-C. Demographic data, organ involvements at the admission, laboratory evaluations for diagnosis, treatment, and follow-up were recorded. We evaluated outcomes by the length of the intensive care unit stay, the total hospitalization period, complications, and mortality. Results: A total of 95 patients diagnosed with MIS-C were evaluated. The mean age was 118.8 (± 52.5) months. 76.8% of the patients had four or more organ systems involved. Seventy-nine patients (83%) were hospitalized in the pediatric intensive care unit (PICU) for a mean of 4.59 days. Seventy-seven (81%) patients received IVIG. A second dose of IVIG was administered to 66.3% of patients. All patients received vitamin D and C supplementation. Six patients who had cardiac involvement or cerebral infarction were treated with plasmapheresis. No patients received steroids. There was no mortality at the end of the follow-up. Conclusions: Favorable outcomes may be obtained with IVIG monotherapy in MIS-C patients. More clinical trials are needed to establish the role of supportive treatments like vitamin D and C in MIS-C management. [ABSTRACT FROM AUTHOR]

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C--two conditions presenting with overlapping symptoms--with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes. [ABSTRACT FROM AUTHOR]

A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin 6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are comparable to those of other hyper-inflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is the SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal–oral transmission. The increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options. Since children with gut dysbiosis may be more susceptible to MIS-C, it is critical to reinforce their microbiome through probiotics supplementation, and plant-fiber-rich diets (prebiotics). Early antibiotic treatment and the use of zonulin antagonists should also be considered. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) occurs after SARS-CoV-2 infection, with gastrointestinal symptoms a prominent feature. This syndrome has been proposed to be triggered by persistent SARS-CoV-2 antigenemia due to increased intestinal epithelial permeability. We obtained evidence for this in this study. Methods: In a single-centre study, we recruited 83 children and analysed blood samples to quantify the circulating markers of increased intestinal permeability following SARS-CoV-2 infection. Publicly available proteomics MIS-C datasets were also accessed to assess the evidence for increased intestinal permeability. We further quantified SARS-CoV-2 antigenemia and the humoral response to SARS-CoV-2 spike protein. Results: Following SARS-CoV-2 infection, healthy children demonstrated no dysregulation of the intestinal epithelial barrier. In MIS-C, considerable increases in markers of epithelial dysfunction were observed, with similar increases noted in febrile controls. Furthermore, we found little evidence of persistent SARS-CoV-2 antigenemia in MIS-C. Conclusions: Our results suggest that although increased intestinal epithelial permeability is a feature of MIS-C, it is not unique to the condition, and persistent SARS-CoV-2 antigenemia does not occur. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to ascertain the most frequent symptoms of COVID-19 infection at first consultation in a pediatric cohort and to devise a predictive model for hospitalization. Methods: This is a retrospective cross-sectional study of 1028 Brazilian patients aged <18 years with SARS-CoV-2 infection in a single reference hospital in the first year of the pandemic. Clinical, demographic, laboratory, and disease spectrum data were analyzed via multivariate logistic regression modeling to develop a predictive model of factors linked to hospitalization. Results: The majority of our cohort were schoolchildren and adolescents, with a homogeneous distribution concerning sex. At first consultation, most patients presented with fever (64.1%) and respiratory symptoms (63.3%). We had 204 admitted patients, including 11 with Pediatric Multisystem Inflammatory Syndrome. Increased D-dimer levels were associated with comorbidities (p = 0.018). A high viral load was observed in patients within the first two days of symptoms (p < 0.0001). Our predictive model included respiratory distress, number and type of specific comorbidities, tachycardia, seizures, and vomiting as factors for hospitalization. Conclusions: Most patients presented with mild conditions with outpatient treatment. However, understanding predictors for hospitalization can contribute to medical decisions at the first patient visit. [ABSTRACT FROM AUTHOR]

Background/Objectives: Multisystem Inflammatory Syndrome in children (MIS-C) is a rare but severe post-infectious complication of COVID-19 that often requires admission to the Pediatric Intensive Care Unit (PICU). The present study aimed to compare the demographic, clinical, and laboratory characteristics of children diagnosed with MIS-C who were admitted to the PICU and those who did not require PICU admission. Methods: Children diagnosed with MIS-C from September 2020 to April 2023 were included in this case-control study. Demographic, clinical, and laboratory data were collected from medical records. Results: Fifty children with MIS-C were included in the study [median (IQR) age: 7.5 (4.3, 11.4) years, 28/50 (56%) males]. Twenty-two (22/50, 44%) children required admission to the PICU. In the multivariate regression analysis, hepatic (OR: 12.89, 95%CI: 1.35–123.41, p-value = 0.03) and cardiological involvement (OR: 34.55, 95%CI: 2.2–541.91, p-value = 0.01) were significantly associated with hospitalization at the PICU. Regarding the laboratory and imaging parameters during the first 48 h from admission, D-dimer levels higher than 4 μg/mL and decreased Left Ventricular Ejection Fraction (LVEF) were associated with an increased risk of PICU admission (OR: 7.95, 95%CI: 1.48–42.78, p-value = 0.02 and OR = 1.28, 95%CI: 1.07–1.53, p-value = 0.01). Children who were admitted to the PICU were more likely to develop complications during their hospitalization (10/22, 45.5% vs. 3/28, 10.7%, p-value = 0.005) and were hospitalized for more days than children in the pediatric ward (median length of stay (IQR): 20 (15, 28) days vs. 8.5 (6, 14) days, p-value < 0.001). Conclusions: The findings of this study indicate that cardiovascular and hepatic involvement and increased D-dimer levels in children with MIS-C might be associated with admission to the PICU. [ABSTRACT FROM AUTHOR]