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BACKGROUND: Recent infection with SARS‑CoV‑2 in children has been associated with multisystem inflammatory syndrome in children (MIS-C). SARS‑CoV‑2 has undergone different mutations. Few publications exist about specific variants and their correlation with the severity of MIS-C. METHODS: This was a single-center, retrospective study including all patients admitted with MIS-C at Rady Childrens Hospital-San Diego between May 2020 and March 2022. Local epidemiologic data, including viral genomic information, were obtained from public records. Demographics, clinical presentation, laboratory values, and outcomes were obtained from electronic medical records. RESULTS: The analysis included 104 pediatric patients. Four MIS-C waves were identified. Circulating variants in San Diego during the first wave included clades 20A to C. During the second wave, there were variants from clades 20A to C, 20G, 21C (Epsilon), 20I (Alpha), and 20J (Gamma). The third wave had Delta strains (clades 21A, 21I, and 21J), and the fourth had Omicron variants (clades 21K, 21L, and 22C). MIS-C presented with similar symptoms and laboratory findings across all waves. More patients were admitted to the pediatric intensive care unit (PICU) (74%) and required inotropic support (63%) during the second wave. None of the patients required mechanical circulatory support, and only two required invasive ventilatory support. There was no mortality. CONCLUSIONS: The various strains of SARS-CoV-2 triggered MIS-C with differing severities, with the second wave having a more severe clinical course. Whether the differences in disease severity across variants were due to changes in the virus or other factors remains unknown.

In December 2019, the so-called "coronavirus disease 2019" (COVID-19) began. This disease is characterized by heterogeneous clinical manifestations, ranging from an asymptomatic process to life-threatening conditions associated with a "cytokine storm". This article (narrative review) summarizes the epidemiologic characteristics and clinical manifestations of COVID-19 and multi-system inflammatory syndrome in children (MIS-C). The effect of the pandemic confinement on vitamin D status and the hypotheses proposed to explain the age-related difference in the severity of COVID-19 are discussed. The role of vitamin D as a critical regulator of both innate and adaptive immune responses and the COVID-19 cytokine storm is analyzed. Vitamin D and its links to both COVID-19 (low levels of vitamin D appear to worsen COVID-19 outcomes) and the cytokine storm (anti-inflammatory activity) are detailed. Finally, the efficacy of vitamin D supplementation in COVID-19 is evaluated, but the evidence supporting vitamin D supplementation as an adjuvant treatment for COVID-19 remains uncertain. [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]

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 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: 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]

Background/Objectives: Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious complication of COVID-19. MIS-C has overlapping features with other pediatric inflammatory disorders including Kawasaki Disease (KD), Macrophage Activation Syndrome (MAS), Toxic Shock Syndrome and sepsis. The exact mechanisms responsible for the clinical overlap between MIS-C and these conditions remain unclear, and biomarkers that could distinguish MIS-C from its clinical mimics are lacking. This study aimed to provide an overview of how proteomic methods, like Mass Spectrometry (MS) and affinity-based proteomics, can offer a detailed understanding of pathophysiology and aid in the diagnosis and prognosis of MIS-C. Methods: A narrative review of relevant studies published up to July 2024 was conducted. Results: We identified 15 studies and summarized their key proteomic findings. These studies investigated the serum or plasma proteome of MIS-C patients using MS, Proximity Extension, or Aptamer-based assays. The studies associated the proteomic profile of MIS-C with laboratory and clinical parameters and/or compared it with that of other diseases including acute COVID-19, KD, MAS, pediatric rheumatic diseases, sepsis and myocarditis or pericarditis following COVID-19 mRNA immunization. Depending on the method and the control group, different proteins were increased or decreased in the MIS-C group. The limitations and challenges in MIS-C proteomic research are also discussed, and future research recommendations are provided. Conclusions: Although proteomics appear to be a promising approach for understanding the pathogenesis and uncovering candidate biomarkers in MIS-C, proteomic studies are still needed to recognize and validate biomarkers that could accurately discriminate MIS-C from its clinical mimics. [ABSTRACT FROM AUTHOR]

At the beginning of the COVID-19 pandemic, it was assumed that children were at low risk of infection and that their infection was milder than adults. With an increase in the number of pediatric cases of SARS-CoV-2 infection associated with manifestations of hyperinflammation, the condition of multisystem inflammatory syndrome in children (MIS-C) was defined. We present a clinical case of a 10-month-old male child hospitalized in the Clinic of Infectious Diseases at University Hospital in Stara Zagora, Bulgaria, with a COVID-19. The patient had a number of co-morbidities, including protein-calorie malnutrition, chronic respiratory failure and bronchopulmonary dysplasia. During the hospital stay, he had an active diarrhea syndrome, with evidence of pneumonia and respiratory failure. In the clinical course, a progressive worsening of the condition with signs of multiple organ failure, increase in inflammatory markers and deterioration of coagulation indicators were observed. Placement in the ICU and the inclusion of artificial pulmonary ventilation were required, but after an 18-day hospital stay, the patient died. In conclusion, this was an acute case of COVID-19 in an infant that started with respiratory and gastrointestinal manifestations that progressed to MIS-C with multiple organ failure leading to death. We believe that the reason for this is the compromised immune status in connection with the highly damaged premorbid terrain and young age.

To date, the pathogenesis of COVID-19 associated multisystem inflammatory syndrome (MIS-C) remains unclear. Despite this, it becomes obvious that the pathogenesis of MIS-C is directly related to a certain immune dysregulation, however, a clear understanding of the mechanisms of this dysregulation has not yet been formulated. In order to identify the cytokine profile in patients with MIS-C, spontaneous and stimulated production of certain cytokines in cell culture was identified. Materials and methods. The study was conducted in the following study groups: group 1 — patients with MIS-C (n = 52); group 2 (comparison group) — patients with COVID-19 associated pneumonia (n = 15); group 3 (control group) — conditionally healthy patients (n = 23). The following stimulating agents were used: S58 — recombinant antigen Spike_SARS-Cov-2; NP is a recombinant NP antigen of the coronavirus SARS-CoV-2 and a standard mitogen. Results. Тhe absence of the initially expected hyperproduction of the main pro-inflammatory cytokines (IL-6, IL-8, TNF-α, etc.) was recorded. Statistically significant developments were recorded between patients of the study groups in the spontaneous production of MCP-1, in particular, the indicated indicator was 40010.82 (19698.1; 64812.1); 643.7 (214.6; 1695.4) and 622.7 (214.6; 1068.1), respectively. The indicated spontaneous hyperproduction of MCP-1 in patients with MIS-C allows us to consider as a probable completely new theory of the pathogenesis of MIS-C associated with dysregulation of the type 2 immune response. The presence of statistically significant differences, primarily in the spontaneous production of this cytokine, can apparently be explained by the presence of genetically determined determinants associated with subsequent dysfunction of the Th2 helper immune response, a potential trigger for which is a previous COVID-19 infection. Thus, further study of the immunopathogenesis of COVID-19 associated MIS-C is required.

The COVID-19 pandemic has introduced challenges in pediatric care, especially due to the emergence of Multisystem Inflammatory Syndrome in Children (MIS-C), a severe condition associated with SARS-CoV-2 infection. This study investigated the impact of hyponatremia and antidiuretic hormone (ADH) secretion corelated to clinical outcomes in these patients. We conducted a retrospective cohort study, including 118 pediatric patients, with a detailed sub-cohort analysis of 53 patients for ADH secretion markers. Hyponatremia, defined by age-specific sodium thresholds, was present in 47.22% of MIS-C cases and 28.04% of COVID-19 cases. Ordinal logistic regression analysis revealed that severe hyponatremia significantly increased the likelihood of more severe clinical outcomes (β = 3.514, p < 0.001). A significant correlation was found between hyponatremia and prolonged hospitalization. For ADH secretion, a predictive model using ridge regression was analysed, which demonstrated that serum sodium level, U/P ratio, and hospitalization duration are key predictors of SIADH. This model fit was assessed using the ROC curve with an AUC of 0.96, indicating reliable model performance. Our findings underscore the significant role of hyponatremia on the clinical severity and hospitalization outcome of COVID-19 and MIS-C in pediatric patients.

Abstract 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

Abstract 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

COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) is a rare autoimmune disorder characterized by a range of polymorphic manifestations, similar to but distinct from other well-known inflammatory syndromes in children. We conducted a retrospective–descriptive study in which we summarized the clinical presentation of, biomarker variations in, and complications occurring in patients diagnosed with MIS-C, admitted to the Emergency Clinical Hospital for Children “Sf. Ioan”, Galati, between July 2020 and June 2024. A total of 36 children met the MIS-C classification criteria according to the WHO-approved case definitions. A total of 41.7% (n = 15) were male and 58.3% (n = 21) were female. The median age of the study group was 4 years (IQR: 1.75–9.25 years). Surgical involvement was suspected in 16.7% (n = 6) of the patients, while 52.8% (n = 19) required intensive care. Clinically, fever was the most common symptom present in 89% (n = 32) of the cases. Gastrointestinal disorders were also common, with 50% (n = 18) presenting with inappetence, 42% (n = 15) with vomiting, and 39% (n = 14) with abdominal pain from admission, which worsened over time. Paraclinically, all patients exhibited signs of inflammation, and 86.1% (n = 31) had hydroelectrolytic and acid–base imbalances. The median hospital stay was 10 days (IQR: 7–12 days), with a stagnant clinical course in most cases. The inflammatory mechanisms in MIS-C, which can affect the secretion of antidiuretic hormone (ADH), were correlated with hydroelectrolytic disturbances and may lead to severe complications. For this reason, it is imperative to evaluate hydroelectrolytic disorders in the context of MIS-C and use diagnostic and prognostic biomarkers to develop effective therapeutic management strategies, ultimately improving the quality of life of affected children.

Multisystem inflammatory syndrome in children (MIS-C) has been reported in patients with inborn errors of immunity (IEI), providing insights into disease pathogenesis. Here, we present the first case of MIS-C in a child affected by Wiskott-Aldrich syndrome (WAS) gene mutation, elucidating underlying predisposing factors and the involved inflammatory pathways. Genetic analysis revealed a frameshift truncating variant in the WAS gene, resulting in WAS protein expression between mild and severe forms, despite a clinical phenotype resembling X-linked thrombocytopenia (XLT). IL-1β secretion by LPS-stimulated peripheral blood mononuclear cells from patient during MIS-C was lower compared to healthy subjects but increased during follow-up. Conversely, the percentage of ASC (apoptosis-associated speck-like protein containing a CARD) specks in the patient’s circulating monocytes during the acute phase was higher than in healthy subjects. The type I interferon (IFN) signature during MIS-C was normal, in contrast to the raised IFN signature measured far from the acute event. This case supports the association of IEI with MIS-C, potentially linked to delayed immune responses to SARS-CoV-2. The XLT phenotype underlies a subclinical immunodysregulation involving the NLRP3 inflammasome and the type-I IFN response. [ABSTRACT FROM AUTHOR]

Abstract Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare complication, which develops within 3–6 weeks after SARS-CoV2 infection. The coronavirus disease 2019 (COVID-19) vaccine was firstly introduced in adults and adolescents and later in patients aged 5–11 years old. Although a reduced incidence of MIS-C and with less severe symptoms has been reported in vaccinated adolescents, there is little knowledge in children younger than 12 years of age. In addition, it is not understood whether MIS-C in vaccinated patients can be triggered by Covid19 vaccination or be secondary to a recent asymptomatic Sars-Cov2 infection. Case presentation We describe the case of a Caucasian 6-year-old girl, one month after double COVID-19 vaccination, who presented fever, acute abdominal pain, rash, pharyngotonsillitis, cheilitis, cervical lymphadenopathy without a prior detected Sars-Cov2 infection. She also had lymphopenia, increase in inflammatory markers, cardiac and pulmonary involvement. Therefore, we dosed both anti Sars-Cov2 Spike and Nucleocapsid antibodies, which were positive and allowed us to confirm the diagnosis of MIS-C. We promptly administered intravenous immunoglobulins and methylprednisone, resulting in the initial regression of fever. During the hospitalization, the child also developed pancreatitis and severe neurological involvement, including irritability, drowsiness, distal tremor, dyskinesia and buccal asymmetry with complete resolution after 2 months. After 3 months from the onset of the symptoms, she reported a transient loss of hair compatible with telogen effluvium. After 12 months of follow-up, she did not show any symptomatic sequelae. Conclusions This case raises the question of whether COVID-19 vaccination may be involved in the pathogenesis of MIS-C in children between the ages of 5 and 11 years old.

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.

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.

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a new disease entity occurring in the pediatric population two to six weeks after coronavirus exposure due to a systemic arteritis. We investigated post-hospital-discharge arterial function at short- and mid-term intervals using pulse wave velocity. We assessed associations between arterial function, left ventricular diastolic and systolic function and left ventricular mass. Materials and methods: Retrospective data collection was carried out on 28 patients with MIS-C with at least two outpatient pediatric cardiology clinic visits post hospital admission. The patients underwent assessment of systemic arterial function and cardiac function. Data included pulse wave velocity between carotid and femoral arteries and echocardiographic assessment of left ventricular systolic function (shortening and ejection fraction, longitudinal strain), diastolic function and left ventricular mass. Results: Pulse wave velocity significantly decreased from visit 1 to visit 2 (5.29 ± 1.34 m/s vs. 4.51 ± 0.91 m/s, p = 0.009). Left ventricular mass significantly decreased from visit 1 to visit 2 (42 ± 9 g/m2.7 vs. 38 ± 7 g/m2.7, p = 0.02). There was a significant negative correlation between the pulse wave velocity and E/A mitral inflow (−0.41, p < 0.05). Conclusions: Children have elevated pulse wave velocity and left ventricular mass in the short-term relative to mid-term values after hospital discharge. These results suggest that MIS-C is associated with transient systemic arterial dysfunction, which, in turn, may play a role in cardiac changes.

Abstract Background Transient erythroblastopenia of childhood (TEC) is an acquired, self-limited pure red cell aplasia that usually occurs in children 4 years old and younger. This clinical condition has been priorly described to be linked to numerous viral and immunologic mechanisms. COVID-19, caused by the coronavirus SARS-CoV-2, was initially discovered in China in December 2019. The disease quickly spread worldwide, resulting in pandemic. Case Presentation This manuscript reports a new clinically relevant condition associated to COVID-19, describing a child with clinical and biochemical signs of Pure Red Blood cells aplasia and complete absence of erythroblasts at the bone marrow needle aspiration with signs of erythrophagocytosis, resembling morphological signs such as in hemophagocytic lymphohistiocytosis (HLH), temporally associated to SARS-CoV-2 infection. Conclusion This report highlights a newly described continuum laboratory and clinical spectrum of immune/hematological dysregulations secondary to SARS-CoV-2. SARS-CoV‐2 infection-linked TEC has never been described in literature, but, according to our findings, should be considered in all the patients with transient erythroblastopenia without congenital red blood cell abnormalities and serology negative for major infections associated with TEC. This condition must be considered in the same spectrum of MIS-C and the inter-links among the two clinical manifestations, as well as a potential interdependence among them, should be considered in the future.

Abstract Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children’s Hospital from January 2022 to June 2023. The median age was 85 (range: 2–188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2–7) days. We observed independent factors related to PICU admission, including CRP $$\ge $$ ≥ 50 (mg/L) (OR 2.52, 95% CI 1.39–4.56, p = 0.002), albumin $$\le $$ ≤ 30 (g/L) (OR 3.18, 95% CI 1.63–6.02, p = 0.001), absolute lymphocyte count $$\le $$ ≤ 2 (× 109/L) (OR 2.18, 95% CI 1.29–3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38–4.01), p = 0.002), and LVEF

We describe 5 children who had Rocky Mountain spotted fever (RMSF) and manifested clinical symptoms similar to multisystem inflammatory syndrome in Sonora, Mexico, where RMSF is hyperendemic. Physicians should consider RMSF in differential diagnoses of hospitalized patients with multisystem inflammatory syndrome to prevent illness and death caused by rickettsial disease.

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare complication, which develops within 3–6 weeks after SARS-CoV2 infection. The coronavirus disease 2019 (COVID-19) vaccine was firstly introduced in adults and adolescents and later in patients aged 5–11 years old. Although a reduced incidence of MIS-C and with less severe symptoms has been reported in vaccinated adolescents, there is little knowledge in children younger than 12 years of age. In addition, it is not understood whether MIS-C in vaccinated patients can be triggered by Covid19 vaccination or be secondary to a recent asymptomatic Sars-Cov2 infection. Case presentation: We describe the case of a Caucasian 6-year-old girl, one month after double COVID-19 vaccination, who presented fever, acute abdominal pain, rash, pharyngotonsillitis, cheilitis, cervical lymphadenopathy without a prior detected Sars-Cov2 infection. She also had lymphopenia, increase in inflammatory markers, cardiac and pulmonary involvement. Therefore, we dosed both anti Sars-Cov2 Spike and Nucleocapsid antibodies, which were positive and allowed us to confirm the diagnosis of MIS-C. We promptly administered intravenous immunoglobulins and methylprednisone, resulting in the initial regression of fever. During the hospitalization, the child also developed pancreatitis and severe neurological involvement, including irritability, drowsiness, distal tremor, dyskinesia and buccal asymmetry with complete resolution after 2 months. After 3 months from the onset of the symptoms, she reported a transient loss of hair compatible with telogen effluvium. After 12 months of follow-up, she did not show any symptomatic sequelae. Conclusions: This case raises the question of whether COVID-19 vaccination may be involved in the pathogenesis of MIS-C in children between the ages of 5 and 11 years old. [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/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]

Background: Kawasaki disease (KD) is a pediatric vasculitis, leading to coronary artery aneurysms (CAAs) in ~4–14%. Attention to the etiology and course of KD was generated by the close mimic of a SARS-CoV-2-induced phenotype, called multisystem inflammatory syndrome in children (MIS-C). Methods: A total of 1179 cases were collected from 2012 with ~50% of cases retrospectively included. Clinical characteristics were described and risk factors for CAA (persistence) were investigated. Phenotypic patterns of the prospectively included KD patients were evaluated. These patterns were also compared to the seronegative KD and seropositive MIS-C cases identified during the SARS-CoV-2 pandemic. Results: KD mostly affected boys and children < 5 years. IVIG resistance, CAAs, and giant CAAs occurred in 24.5%, 21.4%, and 6.6%, respectively. Giant CAAs were significantly more likely to normalize to a normal Z score in patients that were younger than 2.5 years old at the time of initial giant CAA (χ2 test p = 0.02). In our prospective (SARS-CoV-2-seronegative) KD series, there was a diminishing male predominance over time, whereas the proportions of incomplete presentations (p < 0.001) and patients with circulatory shock (p = 0.04) increased since the COVID-19 pandemic. Pre- and post-pandemic KD cases presented with different levels of C-reactive protein, thrombocyte counts, and hemoglobin levels over the years. Compared to pandemic KD, SARS-CoV-2-seropositive MIS-C patients were older (p < 0.001), and more often required intensive care admission (p < 0.001), with a gradual decrease over time between 2020 and 2022 (p = 0.04). KD carried a substantial risk of CAA development in contrast to MIS-C. Conclusion: the phenotypic changes seen over the last twelve years of our prospective follow-up study suggest a spectrum of hyperinflammatory states with potentially different triggering events within this clinical entity. [ABSTRACT FROM AUTHOR]

The clinical significance of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in pediatric patients remains an area of evolving understanding, particularly regarding their utility in the presence or absence of pre-existing heart conditions. While clear cutoff values and established roles in heart failure are understood in adult patients, pediatric norms vary with age, complicating interpretation. Notably, the emergence of multi-system inflammatory syndrome in children (MIS-C) has highlighted the importance of these markers not only in the detection of acute heart failure but also as a marker of disease severity and even as a differential diagnosis tool. This review summarizes current knowledge on the utility of BNP and NT-proBNP in pediatric patients. Their unique physiology, including circulation and compensation mechanisms, likely influence BNP and NT-proBNP release, potentially even in non-heart failure states. Factors such as dynamic volemic changes accompanying inflammatory diseases in children may contribute. Thus, understanding the nuanced roles of BNP and NT-proBNP in pediatric populations is crucial for the accurate diagnosis, management, and differentiation of cardiac and non-cardiac conditions. [ABSTRACT FROM AUTHOR]

Background Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition caused by recent infection with severe acute respiratory syndrome coronavirus 2, but the underlying immunological mechanisms driving this distinct syndrome are unknown. Methods We utilized high-dimensional flow cytometry, cell-free (cf) DNA, and cytokine and chemokine profiling to identify mechanisms of critical illness distinguishing MIS-C from severe acute coronavirus disease 2019 (SAC). Results Compared to SAC, MIS-C patients demonstrated profound innate immune cell death and features of emergency myelopoiesis (EM), an understudied phenomenon observed in severe inflammation. EM signatures were characterized by fewer mature myeloid cells in the periphery and decreased expression of HLA-DR and CD86 on antigen-presenting cells. Interleukin 27 (IL-27), a cytokine known to drive hematopoietic stem cells toward EM, was increased in MIS-C, and correlated with immature cell signatures in MIS-C. Upon recovery, EM signatures decreased and IL-27 plasma levels returned to normal levels. Despite profound lymphopenia, we report a lack of cfDNA released by adaptive immune cells and increased CCR7 expression on T cells indicative of egress out of peripheral blood. Conclusions Immune cell signatures of EM combined with elevated innate immune cell-derived cfDNA levels distinguish MIS-C from SAC in children and provide mechanistic insight into dysregulated immunity contributing toward MIS-C, offering potential diagnostic and therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 varies widely in its presentation and severity, with low mortality in high-income countries. In this study in 16 Latin American countries, we sought to characterize patients with MIS-C in the pediatric intensive care unit (PICU) compared with those hospitalized on the general wards and analyze the factors associated with severity, outcomes, and treatment received. Study Design: An observational ambispective cohort study was conducted including children 1 month to 18 years old in 84 hospitals from the REKAMLATINA network from January 2020 to June 2022. Results: A total of 1239 children with MIS-C were included. The median age was 6.5 years (IQR 2.5-10.1). Eighty-four percent (1043/1239) were previously healthy. Forty-eight percent (590/1239) were admitted to the PICU. These patients had more myocardial dysfunction (20% vs 4%; P < 0.01) with no difference in the frequency of coronary abnormalities (P = 0.77) when compared to general ward subjects. Of the children in the PICU, 83.4% (494/589) required vasoactive drugs, and 43.4% (256/589) invasive mechanical ventilation, due to respiratory failure and pneumonia (57% vs 32%; P = 0.01). On multivariate analysis, the factors associated with the need for PICU transfer were age over 6 years (aOR 1.76 95% CI 1.25-2.49), shock (aOR 7.06 95% CI 5.14-9.80), seizures (aOR 2.44 95% CI 1.14-5.36), thrombocytopenia (aOR 2.43 95% CI 1.77-3.34), elevated C-reactive protein (aOR 1.89 95% CI 1.29-2.79), and chest x-ray abnormalities (aOR 2.29 95% CI 1.67-3.13). The overall mortality was 4.8%. Conclusions: Children with MIS-C who have the highest risk of being admitted to a PICU in Latin American countries are those over age six, with shock, seizures, a more robust inflammatory response, and chest x-ray abnormalities. The mortality rate is five times greater when compared with high-income countries, despite a high proportion of patients receiving adequate treatment. [ABSTRACT FROM AUTHOR]

First described in 2020, multi-system inflammatory syndrome in children (MIS-C) is an, initially life-threatening, disease characterised by severe inflammation and following exposure to SARS-CoV-2. The immunopathology of MIS-C involves a hyperinflammation characterised by a cytokine storm and activation of both the innate and adaptive immune system, eventually leading to multi-organ failure. Several etiological theories are described in literature. Firstly, it is suggested that the gut plays an important role in the translocation of microbial products to the systemic circulation. Additionally, the production of autoantibodies that develop after the initial infection with SARS-CoV-2 might lead to many of its broad clinical symptoms. Finally, the superantigen theory where non-specific binding of the SARS-CoV-2 spike glycoprotein to the T-cell receptor leads to a subsequent activation of T cells, generating a powerful immune response. Despite the sudden outbreak of MIS-C and alarming messages, as of 2024, cases have declined drastically and subsequently show a less severe clinical spectrum. However, subacute cases not meeting current diagnostic criteria might be overlooked even though they represent a valuable research population. In the future, research should focus on adjusting these criteria to better understand the broad pathophysiology of MIS-C, aiding early detection, therapy, and prediction. [ABSTRACT FROM AUTHOR]

MIS-C is a rare, highly inflammatory state resembling incomplete Kawasaki disease, temporarily associated with COVID-19. The pathogenesis is not completely known. RNAseq was carried out on whole blood of six treatment-naïve MIS-C patients. This was compared against RNAseq transcriptomics data of five healthy controls (HC), four Kawasaki Disease (KD) and seven systemic Juvenile Idiopathic Arthritis (sJIA). Using PCA, MIS-C clustered separately from HC, KD and sJIA. Amongst the top 50 significant genes in the three comparisons with HC, KD, and sJIA, common genes were: TMCC2, ITGA2B, DMTN, GFI1B, PF4, QSER1, GRAP2, TUBB1. DSEA revealed that maximum number of hits for overexpressed pathways was for NABA matrisome activation when MIS-C was compared against HC. Cytokine stimulated cellular activation pathways, specifically IL-10 were downregulated. MIS-C had more activated pathways of neutrophil degranulation and acquired immune activation but less of coagulation system or heat-shock system involvement as compared to KD. As compared to sJIA, humoral immune response and complements were activated. Matrisome activation was higher, with increased cell–cell interaction and ECM signalling. This analysis revealed novel insights into the pathogenesis of MIS-C, including the potential role of matrisomes, humoral immune system and down-regulated interleukin-10 pathways. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) infection is present in a latent state in 70–90% of the immunocompetent population, and its reactivation might be triggered by inflammatory conditions such as post-COVID multisystem inflammatory syndrome (MIS-C) or by immunosuppression induced by steroids. The aim of this paper was to highlight the unexpected complications associated with SARS-CoV-2 infection that require a complex clinical approach for accurate diagnosis. Materials and Methods: We present the case of a 4-year-old male patient who, during an initially favorable course of PIMS, experienced symptoms of respiratory failure. Results: The patient initially presented with clinical and paraclinical signs of PIMS with cardiac involvement, for which high-dose corticosteroid therapy was initiated, followed by gradual tapering, along with immunoglobulins, anticoagulants, antiplatelet agents, and symptomatic treatment. After 10 days of favorable progress, the patient's general condition deteriorated, showing tachypnea, desaturation, and a ground-glass appearance on thoracic CT. Negative inflammatory markers and favorable cardiac lesion evolution ruled out MIS-C relapse. The presence of anti-CMV IgM antibodies and viral DNA in the blood confirmed acute CMV infection, likely triggered by prior severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2) infection and secondary immunosuppression due to steroids. Non-specific immunomodulatory treatment was initiated but led to worsening of pulmonary lesions, prompting the initiation of specific antiviral treatment with ganciclovir, resulting in rapid clinical and imaging improvement. Conclusions: CMV infection can be reactivated by immunosuppression induced by corticosteroid therapy for MIS-C and may require specific etiological treatment. [ABSTRACT FROM AUTHOR]

Background: Transient erythroblastopenia of childhood (TEC) is an acquired, self-limited pure red cell aplasia that usually occurs in children 4 years old and younger. This clinical condition has been priorly described to be linked to numerous viral and immunologic mechanisms. COVID-19, caused by the coronavirus SARS-CoV-2, was initially discovered in China in December 2019. The disease quickly spread worldwide, resulting in pandemic. Case Presentation: This manuscript reports a new clinically relevant condition associated to COVID-19, describing a child with clinical and biochemical signs of Pure Red Blood cells aplasia and complete absence of erythroblasts at the bone marrow needle aspiration with signs of erythrophagocytosis, resembling morphological signs such as in hemophagocytic lymphohistiocytosis (HLH), temporally associated to SARS-CoV-2 infection. Conclusion: This report highlights a newly described continuum laboratory and clinical spectrum of immune/hematological dysregulations secondary to SARS-CoV-2. SARS-CoV‐2 infection-linked TEC has never been described in literature, but, according to our findings, should be considered in all the patients with transient erythroblastopenia without congenital red blood cell abnormalities and serology negative for major infections associated with TEC. This condition must be considered in the same spectrum of MIS-C and the inter-links among the two clinical manifestations, as well as a potential interdependence among them, should be considered in the future. [ABSTRACT FROM AUTHOR]

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) has emerged as a severe pediatric complication during the SARS-CoV-2 pandemic, with potential long-term cardiovascular repercussions. We hypothesized that heart rate and blood pressure control at rest and during postural maneuvers in MIS-C patients, months after the remission of the inflammatory syndrome, may reveal long-term autonomic dysfunctions. Methods: We assessed 17 MIS-C patients (13 males; 11.9 ± 2.6 years, m ± SD) 9 months after acute infection and 18 age- (12.5 ± 2.1 years) and sex- (13 males) matched controls. Heart rate and blood pressure variability, baroreflex function, and hemodynamic parameters were analyzed in supine and standing postures. Results: MIS-C patients exhibited reduced heart rate variability, particularly in parasympathetic parameters during standing (pNN50+: 6.1 ± 6.4% in controls, 2.5 ± 3.9% in MIS-C; RMSSD: 34 ± 19 ms in controls, 21 ± 14 ms in MIS-C, p < 0.05), with no interaction between case and posture. Blood pressure variability and baroreflex sensitivity did not differ between groups except for the high-frequency power in systolic blood pressure (3.3 ± 1.2 mmHg2 in controls, 1.8 ± 1.2 mmHg2 in MIS-C, p < 0.05). The MIS-C group also showed lower diastolic pressure–time indices (DPTI) and systolic pressure–time indices (SPTI), particularly in standing (DPTI: 36.2 ± 9.4 mmHg·s in controls, 29.4 ± 6.2 mmHg·s in MIS-C; SPTI: 26.5 ± 4.3 mmHg·s in controls, 23.9 ± 2.4 mmHg·s in MIS-C, p < 0.05). Conclusions: Altered cardiovascular autonomic control may persist in MIS-C patients with, however, compensatory mechanisms that may help maintain cardiovascular homeostasis during light autonomic challenges, such as postural maneuvers. These results highlight the importance of assessing long-term cardiovascular autonomic control in children with MIS-C to possibly identify residual cardiovascular risks and inform targeted interventions and rehabilitation protocols. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in children (MIS-C) is a disease that made its mark in the early days of the COVID-19 pandemic due to the diverse course and symptoms affecting multiple body systems. It is a condition that develops in pediatric patients about 2–6 weeks after contact with a person infected with the SARS-CoV-2 virus. In many instances, MIS-C has caused multiple organ failure, with particularly severe complications involving the cardiovascular system and manifesting as hypotension, various cardiac arrhythmias, myocarditis or coronary artery lesions resembling those seen in Kawasaki disease. Currently, the incidence of MIS-C is about 1–3 per 1000 children, with a decreasing trend in recent years due to the introduction of immunization against the SARS-CoV-2 virus for children as young as 6 months. In our paper, we present the case of a patient with a severe course of MIS-C with numerous cardiovascular and neurological complications, in whom the symptoms of the disease were managed by administering biological treatment. We also present a review of the literature on the subject, which shows how many different facets this disease can have and that physicians still need to remain alert, as there are cases of severe MIS-C, especially in unvaccinated patients. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) is an uncommon illness related with SARS-CoV-2. It generally develops 2-6 weeks after a kid is infected with SARS-CoV-2 and affects many body organs that become inflamed. Objective: This study aimed to investigate the clinical manifestation of multisystem inflammatory syndrome and the effectiveness of different therapeutic modalities. Patients and methods: A prospective cross-sectional observational study was conducted among 75 children with multisystem inflammatory syndrome in Pediatric, Neonatal Intensive Care Unit, Intermediate Care Unit, and Emergency Department at Sohag University Hospital (From June 2022 to February 2024) included 55 confirmed cases and 20 suspected cases. Results: Regarding the reported symptoms, all confirmed cases complained of fever and half of them complained of pulmonary symptoms. 56.4% of cases complained of diarrhea and 1.8% of cases complained of colic. Regarding clinical signs, 45.5% of cases were hypotensive and 52.7% of cases complained of tachypnea. The mean temperature was 38.91 ± 0.49 °C. Regarding heart examination, 50.9% of cases complained of tachycardia. Regarding therapeutic modalities, 36.4% of cases needed combination of antibiotic, solumedrol and IVIG and most of cases (85.5%) received anticoagulants. Conclusion: Early diagnosis and management through routine screening for MIS-C in pediatric patients presenting with prolonged fever, gastrointestinal, respiratory, or cardiovascular symptoms, especially with a history of COVID-19 exposure. Clinical protocols included standardized treatment protocols for MIS-C to ensure timely and effective management. [ABSTRACT FROM AUTHOR]

Aim: Multisystem Inflammatory Syndrome in Children (MIS-C) is a disease developed after about eight weeks of the new coronavirus disease (COVID-19) infection in children. The underlying reason for MIS-C is still unknown. This study aims to assess the nasopharyngeal expressions of Angiotensin-converting enzyme 2 (ACE2), the differentiation 147 receptor cluster (CD147), and the transmembrane serine protease 2 (TMPRSS2) receptors in the MIS-C population. Since these receptors are related to COVID-19 infection, children with previous COVID-19 history were included as a control group. This study is essential for future studies to see if there is any significant expression difference between these receptors in control and MIS-C populations. Materials and Methods: The prospective cohort study took place at Ondokuz Mayıs University. The participants of this study consisted of patients aged 0-18 years who were diagnosed with MIS-C due to COVID-19 infection or patients with only previous COVID- 19 pneumonia but without MIS-C development. A total of 79 cases were registered in this study. Nasopharyngeal samples of children were collected. Total RNA was isolated from all samples. The expression of ACE2, CD147, and TMPRSS2 genes was accessed by real-time quantitative PCR (RT-qPCR). Results: Nasopharyngeal expression of CD147 and TMPRSS2 were not changed in COVID-19 (n=42) and MIS-C (n=37) cases. Expression of ACE2 was increased in the under 10-year-old MIS-C group (n=23) (p=0.004381). Conclusion: Future studies may exclude the nasopharyngeal expression of CD147 and TMPRSS2 to develop MIS-C. Further investigations are required to learn how ACE2 expression contributes to MIS-C development. [ABSTRACT FROM AUTHOR]

Objective In this study, our objective is to compare the demographic, clinical, laboratory, and echocardiographic findings of patients with multisystem inflammatory syndrome in children (MIS-C) and Kawasaki's disease (KD) diagnosed in the prepandemic period. Methods We retrospectively collected data from all pediatric patients who met the Centers for Disease Control and Prevention's MIS-C case definition and who met the American Heart Association's definition of complete KD before the coronavirus disease 2019 pandemic. Results A total of 37 patients diagnosed with MIS-C and 40 patients diagnosed with complete KD were included. Gastrointestinal findings were significantly higher in the MIS-C group than in the KD group (vomiting [ p = 0.009], diarrhea [ p = 0.009]). The incidence of thrombocytopenia (48.6%) was significantly higher in the MIS-C group. Regarding inflammatory markers, procalcitonin and ferritin were significantly higher in the MIS-C group (p = 0.032 and p = 0.006) and the erythrocyte sedimentation rate was higher in the KD group (p < 0.001). Pericardial effusion and mitral valve regurgitation were significantly more frequent in the MIS-C group (p = 0.024 and p = 0.001). Conclusion Although they have similar findings, our current study findings show that MIS-C and KD differ from each other with different clinical and laboratory features. We think that these differences will help clinicians in diagnosis and patient management. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication associated with SARS-CoV-2 infection. The clinical epidemiology of MIS-C is not completely understood in low- and middle-income countries (LMICs) due to limited reporting, including in Asia where there was a substantial burden of COVID-19. We aimed to discuss the challenges of diagnosing MIS-C and factors which may cause children from Asian LMICs to have an increased risk of MIS-C. Methods: Not applicable. Results: The burden of MIS-C in Asian LMICs may be disproportionately high due to underlying risk factors, resource-limited health systems, and the increased infectivity and transmissibility of recent SARS-CoV-2 variants. Complex clinical features of MIS-C contributed to missed or delayed diagnosis and treatment, while underlying risk factors including ethnicity, chronic health conditions, and socioeconomic factors may have predisposed children in Asian LMICs to MIS-C. Conclusions: There was a lack of data on the clinical epidemiology of MIS-C in Asian LMICs during the COVID-19 pandemic, despite reports of higher paediatric mortality rates compared to high-income countries. This highlights the need for LMICs to have strong surveillance systems to collect high-quality and timely data on newly emerging complications associated with a pandemic, such as MIS-C. This will lead to rapid understanding of these emerging complications, and inform clinical management, disease prevention and health system planning.

BackgroundTo identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections.MethodsChildren presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39).ResultsIn the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV.ConclusionsMIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.

BackgroundAutoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown.ObjectiveWe quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections.MethodsCirculating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control.ResultsAmong 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity.ConclusionsHigh levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity.

Background: The clinical features of Multisystem Inflammatory Syndrome in Children (MIS-C) have been well documented, but there is limited data regarding the short term and longitudinal outcomes of children living in rural areas. We report the demographic and clinical features, as well as the multi-specialty follow-up of patients with MIS-C served by a large tertiary care rural health system. Methods: Patients that met the Centers for Disease Control (CDC) case definition of MIS-C admitted between March 1, 2020, and March 31, 2021, were included in this case series. Manual chart review was used to report demographic characteristics, clinical, laboratory and radiologic features during acute hospitalization and multispecialty follow-up, and adherence to follow-up 6–10 weeks after hospital discharge. Results: Twenty-one patients with MIS-C were admitted at our center during the review period. Ninety percent of the cohort required intensive care during hospitalization. Of 19 patients with measured ejection fractions, 52 % had some degree of left ventricular dysfunction on admission; nine patients had electrocardiogram changes on admission. The majority of patients had elevated inflammatory markers during hospitalization. Most patients had resolution of symptoms, improvement in inflammatory markers, and normal cardiac function at the time of discharge. Follow-up with pediatric cardiology, hematology-oncology and infectious disease was indicated for most patients at discharge. Of these, 100 % of patients kept initial follow-up appointments with pediatric cardiology and infectious disease, while 94 % kept initial follow-up appointments with pediatric hematology-oncology. Conclusion: Though most patients were critically ill during hospitalization, the majority had resolution of cardiac abnormalities and inflammatory markers at discharge and timely follow-up with multiple subspecialists after admission with MIS-C.

Objective: This study investigates electrocardiographic (ECG) findings in pediatric patients diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C) during the coronavirus disease-2019 pandemic, offering valuable insights into the diagnostic process. Method: Demographic, clinical, and laboratory data of 71 MIS-C cases and 27 Kawasaki disease cases between January 2019 and December 2021 were retrospectively collected from hospital records, following ethics committee approval. MIS-C diagnosis adhered to World Health Organization criteria, and Kawasaki disease diagnosis followed American Heart Association guidelines. Results: Seventy one MIS-C cases and 27 Kawasaki disease cases were included. MIS-C patients exhibited a significantly shorter duration of fever, higher C-reactive protein levels, and elevated serum cardiac troponin T troponin values compared to Kawasaki disease cases. Transthoracic echocardiographic evaluation revealed specific cardiac abnormalities in MIS-C patients, including mitral regurgitation and aortic regurgitation. ST segment changes, T-wave negativity, and QRS changes were observed significantly in MIS-C patients. Conclusion: Results provide crucial information about the ECG profile of MIS-C cases. Particularly, indicators such as ST segment changes and T-wave negativity play a critical role in distinguishing MIS-C from other similar conditions and understanding its cardiac effects. These data offer valuable clinical markers that can be utilized in the diagnosis and treatment of MIS-C.