Multisystem Inflammatory Syndrome In Children Research Articles

Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children

Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vβ21.3+ T-cell subgroup. Here we apply muti-single cell omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children. Here we show that in Multi-Inflammatory Syndrome in Children (MIS-C), the natural killer cell and monocyte population demonstrate heightened CD95 (Fas) and Interleuking 18 receptor expression. Additionally, TCR Vβ21.3+ CD4+ T-cells exhibit skewed differentiation towards T helper 1, 17 and regulatory T cells, with increased expression of the co-stimulation receptors ICOS, CD28 and interleukin 18 receptor. We observe no functional evidence for NLRP3 inflammasome pathway overactivation, though MIS-C monocytes show elevated active caspase 8. This, coupled with raised IL18 mRNA expression in CD16- NK cells on single cell RNA sequencing analysis, suggests interleukin 18 and CD95 signalling may trigger activation of TCR Vβ21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.

IFIH1 loss of function predisposes to inflammatory and SARS-CoV-2-related infectious diseases.

The IFIH1 gene, encoding melanoma differentiation-associated protein 5 (MDA5), is an indispensable innate immune regulator involved in the early detection of viral infections. Previous studies described MDA5 dysregulation in weakened immunological responses, and increased susceptibility to microbial infections and autoimmune disorders. Monoallelic gain-of-function of the IFIH1 gene has been associated with multisystem disorders, namely Aicardi-Goutieres and Singleton-Merten syndromes, while biallelic loss causes immunodeficiency. In this study, nine patients suffering from recurrent infections, inflammatory diseases, severe COVID-19 or multisystem inflammatory syndrome in children (MIS-C) were identified with putative loss-of-function IFIH1 variants by whole-exome sequencing. All patients revealed signs of lymphopaenia and an increase in inflammatory markers, including CRP, amyloid A, ferritin and IL-6. One patient with a pathogenic homozygous variant c.2807+1G>A was the most severe case showing immunodeficiency and glomerulonephritis. The c.1641+1G>C variant was identified in the heterozygous state in patients suffering from periodic fever, COVID-19 or MIS-C, while the c.2016delA variant was identified in two patients with inflammatory bowel disease or MIS-C. There was a significant association between IFIH1 monoallelic loss of function and susceptibility to infections in males. Expression analysis showed that PBMCs of one patient with a c.2016delA variant had a significant decrease in ISG15, IFNA and IFNG transcript levels, compared to normal PBMCs, upon stimulation with Poly(I:C), suggesting that MDA5 receptor truncation disrupts the immune response. Our findings accentuate the implication of rare monogenic IFIH1 loss-of-function variants in altering the immune response, and severely predisposing patients to inflammatory and infectious diseases, including SARS-CoV-2-related disorders.

Assessment of Repeated Electrocardiogram Findings in Pediatric Multisystem Inflammatory Syndrome Associated with COVID-19

Background: Cardiac involvement, stemming from the novel multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease-2019 (COVID-19), leads to common and severe complications. Objectives: The aim of this study is to compare and evaluate repetitive electrocardiogram (ECG) results and laboratory indicators in children diagnosed with MIS-C upon their initial hospital admission. Methods: This prospective, single-center study, conducted between December 2020 and October 2022, included repeated electrocardiographic and laboratory tests. Changes in the ECG over the course of the disease were regularly recorded for three months. Results: This study included 72 patients, 25 of whom were female. Mitral regurgitation and left ventricular systolic dysfunction were observed in 25% of the patients. Statistically significant differences (P < 0.05) were detected among the serial measurements of absolute neutrophil-lymphocyte count, CRP, procalcitonin, ESR, D-dimer, troponin T, pro-BNP, ferritin, and interleukin-6. Significant differences were also observed in heart rate, PR interval, QRS duration, QT duration, Fredericia QTc, JT interval, presence of sinus tachycardia, presence of first-degree AV block, presence of wide QRS, abnormal QRS axis, abnormal T axis, long QTc, and ST-T changes (P < 0.05). Additionally, significant differences were noted in the absolute lymphocyte count, troponin levels, and ferritin levels between patients with prolonged abnormal ECG findings and those whose ECG findings were normal or had returned to normal. Furthermore, statistically significant differences were observed in absolute lymphocyte count, ferritin, and fibrinogen levels among the other four groups (P < 0.05). Conclusions: Electrocardiogram findings in patients measured serially appear to improve over time. Since patients with MIS-C may experience ECG abnormalities that could lead to arrhythmias, close monitoring and the establishment of standardized approaches are essential. Long-term ECG abnormalities were associated with a decrease in absolute lymphocyte count and elevated levels of troponin, ferritin, and fibrinogen.

Should aortic stiffness parameters be used in MIS-C patient follow-up?

We evaluated the short- and long-term effects of multisystem inflammatory syndrome in children (MIS-C) on their cardiovascular system. The study population consisted of 38 MIS-C patients and 55 control patients. Standard echocardiographic measurements and aortic stiffness parameters were compared between the two groups at different time points. During the standard echocardiographic examination at the time of diagnosis, mitral valve insufficiency was detected in 42% of the cases, left ventricular systolic dysfunction in 36%, aortic valve insufficiency in 3%, tricuspid valve insufficiency in 13%, and coronary artery dilatation in 31%. The ejection fraction, pulse pressure of the experimental group were significantly lower than the control group (p < 0.01, p = 0.045, respectively). When aortic stiffness parameters were compared, it was seen that the parameters increased in the experimental group and the difference was significant for aortic distensibility. (p = 0.105, p = 0.029 respectively). When comparing the experimental group's results at diagnosis and at the sixth month, there was a decrease in aortic stiffness parameters at the sixth month compared to the time of diagnosis, but the difference wasn't significant (p = 0.514, p = 0.334). However, no statistically significant difference was detected when comparing the aortic distensibility results of the experimental group with the control group at the sixth month (p = 0.667). Our results showed that many pathological echocardiographic findings detected at diagnosis in MIS-C patients returned to normal within six months. Therefore, we believe that the cardiovascular follow-up period of MIS-C cases should be at least six months.

Cerebral Malformations Related to Coronavirus Disease 2019 during Pregnancy

AbstractThe pandemic of severe-acute-respiratory-syndrome-related coronavirus (SARS-Cov-2) has shown a wide spectrum of possible consequences in children, ranging from asymptomatic patients to the development of severe conditions, such as multisystem inflammatory syndrome in children and encephalopathies related to cytokine storm. Specifically, neurological and neuroimaging abnormalities, ranging from mild-to-the severe ones, have been documented in children as well, such as postinfectious immune-mediated acute disseminated encephalomyelitis, myelitis, neural enhancement, cranial nerve enhancement, and cortical injury, also without neurological symptoms. Considering the neurotropism of coronaviruses and SARS-Cov-2, which has been well described in the literature, we reviewed the literature reporting possible cerebral malformation in neonates due to the infection of SARS-Cov-2 in pregnancy. Coronavirus disease 2019 (COVID-19) during pregnancy might develop cerebral disorders in several ways. Articles in English in the literature were screened using the following search terms: (1) “brain malformations” AND “COVID-19”; (2) “cerebral malformations” AND “COVID-19”; (3) brain malformations AND “Sars-Cov-2”; (4) “cerebral malformations “AND “Sars-Cov-2.” Considering the congenital brain malformation found in newborns exposed to infection of SARS-Cov-2 pre- or neonatally, we identified one paper which reported three neonates with cerebral malformation. Although sporadic, cerebral malformations like atypical signals in white matter with delayed myelination, brain dysplasia/hypoplasia with delayed myelination, and unusual signals in the periventricular regions have been documented.

Serum proteomics reveals hemophagocytic lymphohistiocytosis-like phenotype in a subset of patients with multisystem inflammatory syndrome in children

Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.

The Association Between Early Initiation of Systemic Corticosteroids and the Hospital Length of Stay in Patients With Multisystem Inflammatory Syndrome in Children.

Patients with multisystem inflammatory syndrome in children (MIS-C) often require hospital admission. Treatment of MIS-C has included intravenous immunoglobulin, systemic corticosteroids, and/or immunomodulators. There is no standardized approach to when steroids should be initiated during treatment. The study objective was to determine whether early initiation of steroids in patients with MIS-C is associated with the duration of hospital length of stay (LOS). This is a single-center retrospective cohort study of patients younger than 21 years who were hospitalized with MIS-C between March 2020 and September 2021 and received steroids. Cases were obtained from an institutional MIS-C log. Patients with culture proven sepsis and/or those who received intravenous immunoglobulin or steroids within the previous 30 days were excluded. We used a multivariable linear regression model, controlling for potential confounders, to assess the association between early steroids and LOS. A total of 56 patients hospitalized with MIS-C were identified; 38 received systemic corticosteroids and were included in the study. The mean time from admission to steroid administration was 9.8 hours (SD = 7.7) in the early group and 44.6 hours (SD = 14.2) in the late group. There was a statistically significant difference in baseline characteristics of patients receiving early versus late steroids in initial C-reactive peptide, procalcitonin, brain natriuretic peptide, and cardiac dysfunction. After controlling for confounders, initiating steroids within 24 hours of admission for MIS-C was associated with a decreased hospital LOS: in patients treated with early steroids, LOS was 58.3 hours less (95% confidence interval, -100.0 to -16.6; P = 0.007) than in those who received late steroids. Among patients with MIS-C, initiating systemic corticosteroids within 24 hours of admission was associated with decreased hospital LOS.

Multisystemic inflammatory syndrome in children and the BNT162b2 vaccine: a nationwide cohort study.

This research demonstrates that vaccinating children and adolescents against COVID-19 has reduced the risk of MIS-C during the study period. • Most of the published literature regarding vaccine effectiveness is based on case-control studies, which are limited due to small sample sizes and the inability to fully estimate the risk of MIS-C among vaccinated and unvaccinated children and adolescents. • The known underestimation of COVID-19 diagnosis among children and adolescents is challenging, as they often have few to no symptoms. • Significant risk difference was found in favor of the vaccinated group, even after including extreme assumptions regarding the underdiagnosed COVID-19 rate. • During this nationwide study period, it was found that vaccinating children and adolescents reduced the risk of MIS-C and its complications.

Proteomic mapping identifies serum marker signatures associated with MIS-C specific hyperinflammation and cardiovascular manifestation

Multisystem inflammatory syndrome in children (MIS-C) shares several clinical and immunological features with Kawasaki Disease (KD) and pediatric hyperinflammation, but the immuno-phenotypic overlap among these clinical mimics is still incompletely understood. Here we analyzed serum samples from treatment-naïve patients with MIS-C (n = 31) and KD (n = 11), pediatric hyperinflammation (n = 13) and healthy controls (HC, n = 10) by proximity extension assay (PEA) to profile 184 blood biomarkers. Collectively, immunophenotypic overlap between MIS-C and hyperinflammation exceeds overlap with KD. Overexpression of IL-17A in MIS-C and KD could best separate these conditions from hyperinflammatory conditions, while those were hallmarked by overabundance of adenosin deaminase and IL-18. Depletion in serum TNF-related subfamily member 9 (TNFRSF9) and apoptosis inducing ligand (TRAIL) linked with cardiovascular manifestations and myocarditis in MIS-C. Altogether, our analysis highlights important differences in molecular marker signatures also across different MIS-C and KD cohorts and suggests several previously unidentified molecular associations in context of cardiovascular inflammation.

Multisystem inflammatory syndrome in children: A review.

To comprehensively review the literature on multisystem inflammatory syndrome in children (MIS-C). Narrative review of relevant studies published between April 2020 and January 2024. MIS-C is a SARS-CoV-2-related hyperinflammatory syndrome developing 2-6 weeks after COVID-19 in genetically susceptible individuals. Persisting fever, mucocutaneous manifestations, GI and cardiac involvement, together with lymphopenia and elevated inflammatory and cardiac markers are the main clinical features. It is believed to recognise some pathogenetic and clinical overlap with Kawasaki disease. New case definitions have been proposed after an assessment of the diagnostic performance of existing criteria; epidemiological criterion is however progressively losing its usefulness as the pandemic turns into an endemic and in the areas with the highest rates of COVID-19 vaccination. Current guidelines recommend both intravenous immunoglobulin and glucocorticoids in the first-line immunomodulatory treatment, mainly based on comparative retrospective cohorts; the actual role of biologics remains to be adequately established. Strict follow-up is mandatory, especially for those with severe cardiac involvement, as longitudinal studies evaluate the long-term evolution of cardiac damage. In this paper, we review the epidemiological, pathogenetic, clinical and prognostic features of MIS-C, and outline the main questions which still remain unanswered after more than 3 years of research.

Atypical Dermatological Presentation of Multisystem Inflammatory Syndrome in a Child with Polyarticular JIA: A Case Report

Multisystem inflammatory syndrome in children (MIS-C) is an inflammatory process that occurs after infection with SARS-CoV-2 virus. In this syndrome children usually present with fever, rash, abdominal pain, diarrhea or vomiting, hypotension and shock. Children may need urgent care if heart, blood vessels or other vital organs are involved. Poly-articular Juvenile Idiopathic arthritis is a subset of JIA defined by presence of arthritis of five or more joints within 6 months of disease onset along with other criteria of JIA. In this case report we report mucocutaneous manifestation of MIS-C in a child with poly-articular rheumatoid factor (RF) negative JIA case. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 86-88

Abnormal innate immune responses and associated genetic factors in Multisystem Inflammatory Syndrome in Children (MIS-C)

Abstract Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of COVID-19 characterized by multi-lineage immune activation and multi-organ system involvement. While baseline immunophenotypes have been characterized, innate immune cell functionality and genetic risk factors remain poorly understood. To address these knowledge gaps, we assessed inflammatory immune responses in children with MIS-C (n = 33) relative to healthy controls (n = 5). We found that Toll like receptor (TLR) signaling is severely dampened in peripheral blood cells in the MIS-C group, with weak cytokine responses to LPS stimulation and increased baseline gene expression of TLR negative regulators, compared to controls. We also found that the cytokine response to LPS was abnormally heterogeneous in the MIS-C group. In particular, cytokine response outliers were enriched for rare and potentially deleterious variants in the lysosomal trafficking regulator (LYST) locus. These LYST variants were associated with markers of lysosomal and mitochondrial dysfunction, altered energy metabolism, and low levels of TLR negative regulator expression. Improved knowledge of immune dysfunctions associated with MIS-C and risk factors may help explain aspects of MIS-C and other manifestations of long COVID and identify targets for therapy of MIS-C and other hyperinflammatory syndromes in children.

Multisystem Inflammatory Syndrome in Children (MIS-C) in a Low-income Country: What Treatment Should be Adopted in Case of a Lack of Immunoglobulin?

In multisystem inflammatory syndrome (MIS-C), children typically present high-grade fever, gastrointestinal symptoms, Kawasaki-like symptoms, and even a toxic shock-like syndrome days to weeks after recovering from SARS-CoV-2 infection. It is important to raise awareness of this condition in order to have early diagnosis and immediate treatment of patients. We have, herein, reported 44 cases of MIS-C with various risk factors and symptoms. Furthermore, we have emphasized the efficacy of experience in treating children with MIS-C with high-dose corticosteroids as an alternative to immunoglobulin in low-income countries. We conducted a targeted survey of MIS-C from early May 2020 to October 2022 on 44 children and adolescents with characteristics of multisystem inflammatory syndrome admitted to the pediatric department of the university hospital center in Oujda, Morocco, to which patients diagnosed with MIS-C were referred. The case definition included six criteria: serious illness leading to hospitalization, age under 18 years, fever of at least 24 hours, laboratory evidence of inflammation, multi-organ involvement, biological inflammatory syndrome, and evidence of coronavirus infection based on polymerase chain reaction, antibody testing or exposure to people with COVID-19 in the past month. The criteria used to diagnose myocarditis were impaired left ventricular function, central mitral leak, and elevation of BNP or pro-BNP. Coronary involvement was assessed by the z-score and the criteria for its presence was a z-score equal to or greater than 2.5. Our study included 44 children and adolescents with MIS-C in our hospital, with male predominance (79%) and a median age of six years. Cardiovascular involvement was present in 91%, mucocutaneous in 78%, gastrointestinal in 70%, hematologic in 84%, and respiratory in 2% of patients. Coronary abnormalities (z-score ≥ 2.5) were documented in 21 cases (48%). Glucocorticoids were frequently used in comparison to immunoglobulin, which were uncommonly available and expensive. The therapeutic protocol that was adopted was high doses of short-term prednisone (Cortancyl) at 4mg/kg/day for 4 days. Favorable outcome was noted in all patients over a 2-year period.

Role of electrocardiometry in hemodynamic assessment of children with shock in multisystem inflammatory syndrome following COVID-19: A single-center prospective observational study

Background: The hemodynamic profile in multisystem inflammatory syndrome in children (MIS-C) has not been well described. Therefore, we conducted the study utilizing electrocardiometry (EC) to assess the hemodynamic characteristics in MIS-C patients presenting with shock. Subjects and Methods: This pilot prospective observational study was conducted in the pediatric intensive care unit of a tertiary care hospital. Children between 2 months and 18 years meeting the WHO criteria for MIS-C presenting with shock during second COVID-19 pandemic were included in the study. All patients underwent measurement of hemodynamic profile with EC for the initial 48 h of enrollment. Based on EC assessment at enrolment, the systemic vascular resistance index (SVRi) of 1000–1600 dyn s/cm5/m2 was regarded as normal. The hemodynamic categorization was defined as vasodilatory shock in EC (VDEC) (SVRi &lt;1000 dyn s/[cm5/m2]) and vasoconstrictive shock in EC (VCEC) (SVRi &gt; 1600 dyn s/[cm5/m2]). Results: Thirty-one children met the WHO case definition of MIS-C during the study period. Sixteen children with shock were enrolled and studied. Clinically, 7 (43.75%) children had cold shock, whereas 9 (56.25%) had warm shock. The measured baseline (mean [standard deviation]) hemodynamic variables were cardiac index (CI) of 6 ± 1.41 L/min/m2, stroke volume variation of 23% ±9.6%, SVRi of 954.75 ± 263.35 dyn s/(cm5/m2), and thoracic fluid content of 51.18 ± 17.26 ml. VDEC was the predominant manifestation (87.5%) based on EC. Conclusions: Vasodilatory shock was the predominant phenotype observed in critically ill children with MIS-C with shock by EC assessment.

Risk Factors for Cardiac Involvement in Children with Severe Acute Respiratory Syndrome Coronavirus 2-related Multisystem Inflammatory Syndrome in Children: A Prospective Observational Study

Introduction: Our study aims to investigate the association between cardiac involvement in multisystem inflammatory syndrome in children (MIS-C) and the patient’s epidemiological, clinical, and investigative profile. Identifying such associations could facilitate the early detection and management of cardiac complications, potentially leading to improved patient outcomes. Materials and Methods: The study was conducted as a prospective observational study at SAT Hospital, Government Medical College, Thiruvananthapuram. It included all children aged 0–12 years admitted during the study period who met the criteria for the diagnosis of MIS-C as per the guidelines provided by the World Health Organization. Exclusion criteria comprised children with a confirmed alternative diagnosis, preexisting heart disease, and those whose parents declined consent for participation. Despite aiming for a sample size of 55 based on previous studies, only 50 samples were obtained within the study period. Ethical considerations were met and no funding was involved in our study. A well-structured pro forma was used for data collection. Results: Our study included 50 children aged under 12 years, with a median age of 7 years, and an interquartile range of 4.6 years. Of these participants, 54% were male, and the remaining 46% were female. According to the operational definition utilized in our study, 62% of the children exhibited cardiac involvement, while 38% had a normal cardiac status. In our investigation, the median values for C-reactive protein and erythrocyte sedimentation rate were found to be 10 mg/dl and 60 mm/h, respectively. Furthermore, the median platelet count was observed to be 1.87 lakhs/mm3, while the median absolute lymphocyte count was recorded as 1472 cells/mm3. Serum albumin and NT-pro BNP were identified to have a statistically significant association with cardiac involvement, exhibiting significance at the 1% level. Conclusion: Our findings suggest that serum albumin and NT-pro BNP have a statistically significant association with cardiac involvement in MIS-C. Furthermore, hemodynamic instability in MIS-C may result primarily from vasculopathy rather than cardiac dysfunction.

Role of Vitamin D and Vitamin D Polymorphisms in COVID-19 Risk and Severity in Children: A Systematic Review.

The role of vitamin D in the susceptibility to coronavirus disease 2019 (COVID-19) disease has been investigated since the beginning of the pandemic, but there is still scarce data on children. We investigated the impact of vitamin D status and the related genetic variants on COVID-19 vulnerability and severity of the disease in children. A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to identify reports on vitamin D status and genetic polymorphisms, their association with the susceptibility of children to COVID-19 and multisystem inflammatory syndrome in children (MIS-C), and the effect of supplementation on the clinical course. Of an initial total of 279 articles, 26 studies,published between September 2020 and May 2023, were finally includedin this review according to inclusion criteria. Quantitative data provided by 11 studies revealed that 43.05% of pediatric COVID-19 patients had low vitamin D levels. Mean serum 25(OH)D levels were observed to be significantly low in COVID-19 cases, with an estimated pooled mean value of 17 ng/mL, as provided by 16 studies. Vitamin D deficiency and the vitamin D receptor (VDR) FokI polymorphism may suggest independent risk factors for susceptibility to COVID-19 in the pediatric population. The 25(OH)D level may constitute a significant biomarker associated with the COVID-19 severity and MIS-C. While supplementation of COVID-19 cases with vitamin D showed favorable results, the effect on the outcome of the disease remains uncertain.

Knowledge framework of intravenous immunoglobulin resistance in the field of Kawasakidisease: A bibliometric analysis (1997-2023).

Kawasaki disease (KD) is an autoimmune disease with cardiovascular disease as its main complication, mainly affecting children under 5 years old. KD treatment has made tremendous progress in recent years, but intravenous immunoglobulin (IVIG) resistance remains a major dilemma. Bibliometric analysis had not been used previously to summarize and analyze publications related to IVIG resistance in KD. This study aimed to provide an overview of the knowledge framework and research hotspots in this field through bibliometrics, and provide references for future basic and clinical research. Through bibliometric analysis of relevant literature published on the Web of Science Core Collection (WoSCC) database between 1997 and 2023, we investigated the cooccurrence and collaboration relationships among countries, institutions, journals, and authors and summarized key research topics and hotspots. Following screening, a total of 364 publications were downloaded, comprising 328 articles and 36 reviews. The number of articles on IVIG resistance increased year on year and the top three most productive countries were China, Japan, and the United States. Frontiers in Pediatrics had the most published articles, and theJournal of Pediatricshad the most citations. IVIG resistance had been studied by 1889 authors, of whom Kuo Ho Chang had published the most papers. Research in the field was focused on risk factors, therapy (atorvastatin, tumor necrosis factor-alpha inhibitors), pathogenesis (gene expression), and similar diseases (multisystem inflammatory syndrome in children, MIS-C). "Treatment," "risk factor," and "prediction" were important keywords, providing a valuable reference for scholars studying this field. We suggest that, in the future, more active international collaborations are carried out to study the pathogenesis of IVIG insensitivity, using high-throughput sequencing technology. We also recommend that machine learning techniques are applied to explore the predictive variables of IVIG resistance.

Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1β, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.

A case report on Multisystem Inflammatory Syndrome in Children (MIS-C) with myocarditis

Multisystem Inflammatory Syndrome in Children (MIS-C) is a serious condition that can occur after a SARS-CoV-2 infection, commonly known as COVID-19. It involves fever, organ dysfunction, and increased inflammation markers. It was initially described as a post- infection complication of SARS-CoV-2 virus. With the development of vaccines and the efforts to control the spread of the virus, the incidence of MIS-C has decreased. There is no specific test to diagnosis a patient with this condition For patients with symptoms of MIS-C, clinicians perform a thorough evaluation, which may include blood tests, scans etc. Patients are also tested for the presence of antibodies to SARS-CoV2, the virus that causes COVID-19. When it comes to the treatment of Multisystem Inflammatory Syndrome in Children (MIS-C), it typically involves a multidisciplinary approach and may vary depending on the severity of the condition. Treatment often includes hospitalization for close monitoring and supportive care. This can involve intravenous fluids, medications to reduce inflammation, and management of specific organ complications. In some cases, additional interventions such as immunoglobulin therapy or steroids may be used.

Gastrointestinal and Hepatic Manifestations of COVID-19 in Children: A Systematic Review and Meta-analysis.

Children with COVID-19 may present with gastrointestinal (GI) symptoms and liver dysfunction. To determine the type and prevalence of gastrointestinal (GI) and hepatic manifestations of COVID-19 in children and its association with severity of illness. A systematic literature search was done from inception until January 4, 2021 using PubMed, Cochrane Library, Google Scholar and prepublication repositories with no language restrictions. Studies that reported the demographic and clinical features of children with COVID-19 and provided data on their GI and hepatic signs and symptoms were included. Prevalence of GI and hepatic manifestations were pooled using Stata14. We included 58 studies with total of 4497 participants. Overall, one-third of children with COVID-19 presented with at least one GI symptom (33.8%; 95% confidence interval (CI) 23.0, 45.4; I2 97.5%; 42 studies, 3327 participants) with abdominal pain, nausea or vomiting, and diarrhea each occurring in approximately 20%. Children with severe COVID-19 were more likely to present with GI symptoms (odds ratio 2.59; 95% CI 1.35, 4.99; I2 24%; 4 studies, 773 participants). The pooled prevalence of elevated transaminases was 11% for both AST (11.3%, 95% CI 4.9, 19.3; I2 74.7%; 11 studies, 447 participants) and ALT (11.2%, 95% CI 7.1, 16.0; I2 40.8%; 15 studies, 513 participants). Hepatic findings such as jaundice (2-17%), hepatomegaly (2%) or behavioral changes (2%) from hepatic encephalopathy were variably reported by a few studies.The degree of heterogeneity was not improved on exclusion of studies with poor quality, but markedly improved on subgroup analysis according to geographical region and presence of MIS-C. Studies from China showed that children with COVID-19 had significantly lower pooled prevalence for any of the GI symptoms with low degree of heterogeneity, particularly for diarrhea, nausea/vomiting, and abdominal pain, all of which had I2 of 0%. Those with multisystem inflammatory syndrome in children (MIS-C) had significantly more common GI symptoms and increased transaminases than those without. One-third of children with COVID-19 exhibit at least one GI symptom and more likely present in those with severe disease. Elevated transaminases were present in 10%. Prevalence of GI and hepatic manifestations were higher among children with MIS-C.