Syndrome In Children Research Articles

Severity predictors for multisystemic inflammatory syndrome in children after SARS-CoV-2 infection in Vietnam

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 ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge $$\\end{document} 50 (mg/L) (OR 2.52, 95% CI 1.39–4.56, p = 0.002), albumin ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le $$\\end{document} 30 (g/L) (OR 3.18, 95% CI 1.63–6.02, p = 0.001), absolute lymphocyte count ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le $$\\end{document} 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 < 60 (%) (OR 2.48, 95% CI 1.28–4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le $$\\end{document} 2 (× 109/L) (OR 2.48, 95% CI 1.10–5.61, p = 0.029), albumin ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le $$\\end{document} 30 (g/L) (OR 2.53, 95% CI 1.22–5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12–4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes.

Specific brain MRI features of constitutional mismatch repair deficiency syndrome in children with high-grade gliomas.

Children with constitutional mismatch repair deficiency (CMMRD) syndrome have an increased risk of high-grade gliomas (HGG), and brain imaging abnormalities. This study analyzes brain imaging features in CMMRD syndrome children versus those with HGG without CMMRD. Retrospective comparative analysis of brain imaging in 30 CMMRD children (20 boys, median age eight years, 22 with HGG), seven with Lynch syndrome (7 HGG), 39 with type 1 neurofibromatosis (NF1) (four with HGG) and 50 with HGG without MMR or NF1 pathogenic variant ("no-predisposition" patients). HGG in CMMRD and Lynch patients were predominantly hemispheric (versus midline) compared to NF1 and no-predisposition patients (91% and 86%, vs 25% and 54%, p = 0.004). CMMRD-associated tumors often had ill-defined boundaries (p = 0.008). All CMMRD patients exhibited at least one developmental venous anomaly (DVA), versus 14%, 10%, and 6% of Lynch, NF1, and no-predisposition patients (p < 0.0001). Multiple DVAs were observed in 83% of CMMRD patients, one NF1 patient (3%), and never in other groups (p < 0.0001). Cavernomas were discovered in 21% of CMMRD patients, never in other groups (p = 0.01). NF1-like focal areas of high T2-FLAIR signal intensity (FASI) were more prevalent in CMMRD patients than in Lynch or no-predisposition patients (50%, vs 20% and 0%, respectively, p < 0.0001). Subcortical and ill-limited FASI, possibly involving the cortex, were specific to CMMRD (p < 0.0001) and did not evolve in 93% of patients (13/14). Diffuse hemispherically located HGG associated with multiple DVAs, cavernomas, and NF1-like or subcortical FASI strongly suggests CMMRD syndrome compared to children with HGG in other contexts. The radiologic suggestion of CMMRD syndrome when confronted with HGGs in children may prompt genetic testing. This can influence therapeutic plans. Therefore, imaging features could potentially be incorporated into CMMRD testing recommendations. Using imaging to detect CMMRD syndrome early may improve patient care. CMMRD features include: hemispheric HGG with multiple developmental venous anomalies and NF1-like or subcortical areas with high T2-FLAIR intensity. We propose novel imaging features to improve the identification of potential CMMRD patients.

Beaten to Blindness: Battered Baby Syndrome

Introduction: A battered child is one who sustains repetitive physical injuries due to non-accidental violence inflicted by a parent or guardian. Child abuse encompasses behaviors exposing the child to various forms of physical or sexual abuse, neglect, or emotional misconduct. Typically, battered child syndrome is diagnosed through a disparity between the history provided by the child's caregivers and the findings of clinical examination. Case details: An 18-month-old girl child was admitted to a tertiary care hospital, presenting with a four-day history of fever, vomiting for two days and a seizure episode. The child had a history of head injury one week ago, resulting in transient unconsciousness. Upon examination, multiple healed and fresh injuries were observed on the face, hands, and right thigh. CT brain revealed hypodensity areas with a mildly displaced fracture of the left frontal bone. Fundus examination identified bilateral multiple intraretinal hemorrhages and papilledema. X-ray showed a fracture of the right proximal tibia. The child required ventilator support during the hospital stay, and subsequently, developed retinal blindness. The child was managed accordingly. Discussion: The classical feature of Battered Baby Syndrome is the discrepancy between the nature of injuries and the history provided, and the delay between the injury and medical attention. The parental risk factors for child abuse are poverty, social isolation, drug addiction, violent environment, family history of abuse, communication skills deficit and the child related risk factors are children with special needs, children with behavior problems, bonding deficit. etc. Conclusion: The current case sheds light on the unfortunate prevalence of this condition within the Indian context, urging point-of-care health providers to stay vigilant and informed about child abuse patterns in the community. It serves as a crucial reminder of the responsibility we all share in safeguarding the well-being of children.

Acute encephalitis with flaccid paralysis following an adenoviral infection presenting as a rare variant of Guillain Barre syndrome in a school-age child

Acute encephalitis with flaccid paralysis following an adenoviral infection presenting as a rare variant of Guillain Barre syndrome in a school-age child

Follow Up of Cardiovascular Affection in Covid-19 Pediatrics Survivors

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 is a rare complication of (SARS-CoV-2) infection. Presenting (4–6) weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation which is mostly due to post infection immune reaction. Aim of the Work to evaluate cardiac outcomes 6 months after initial presentation with MIS-C associated with cardiac affection. Patients and Methods This was a retrospective cohort study on 28 patients (19 boys &amp; 9 girls) who were diagnosed as multi system inflammatory syndrome in children (MIS-C) related to COVID19 six months ago at children`s hospital, Ain shams university from January 2021 to October 2021. All patients were subjected to the following: (demographic data, clinical signs and symptoms, laboratory investigations) in the acute phase (obtained from patient’s medical records) and at follow up after 6- months. Results in our study all patients fulfilled criteria of MIS-C presented with fever, shock or cardiac dysfunction and gastrointestinal symptoms in addition to conjunctivitis and skin rash. Our patients were presented with hypotension with mean systolic blood pressure (87) mmHg &amp; mean diastolic blood pressure (48) mmHg. Regarding symptoms: vomiting was seen in (60.7%), diarrhea in (32.1%), conjunctivitis in (82.1%) and cardiovascular abnormalities were seen in (100%) in the form of (myocardial dysfunction in (50%), coronary dilatation in (28.8%), valvular regurgitation in (100%) and pericardial effusion in (7.2%)). After 6 months there was significant improvement regarding vital signs. Regarding laboratory findings: at time of presentation most of the patients had high CRP, high troponin, and high CK-MB. On follow up after 6 months, all patients had normal values. Conclusion Our follow up study suggests that functional recovery and coronary outcomes are good in multisystem inflammatory syndrome in children.

Cardiac Follow up of Pediatric Patients Presented with Covid-19 Cardiovascular Affection

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 carditis, presenting 4–6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. Aim of the Work To Follow up of Pediatric Patients Presented with Covid-19 Cardiovascular Affection. Patients and Methods This was an analytical Prospective Cohort study conducted on 33 patients with post COVID-19 infection. all patients were subjected to the following:(demographic data, clinical signs &amp; symptoms, laboratory investigations and Echocardiogrsphy at presentation, 1,6 weeks and 3months follow up from January 2021 to August 2021 to evaluate the short and mid- term effect of COVID-19 infection on cardiac function, and outcomes for pediatric multisystem inflammatory syndrome related to covid-19. Results In our study all patients fulfilled criteria of MIS-C presented with Kawasaki disease(KD)- like symptoms and gastrointestinal symptoms in addition to fever with shock or cardiac dysfunction. Our patients were presented with the following vital data: tacycardia with mean of 132.82 (18.74) beat/minute, hypotension with mean of 88.03 (14.06) (mmhg) for systolic blood pressure &amp; mean of 49.39 (14.78) mmhg for diastolic blood pressure, spo2 mean 96.27 (2) %, high grade fever of mean 38.36(0.79). KD-like features were seen in many patients (skin rash in 66.7%, conjunctivitis in 75.8% and Cardiovascular abnormalities were seen in 100% e.g. (myocardial dysfunction, valvular regurgitation, pericardial effusion and shock. Our MIS-C patients had signs and symptoms of an inflammatory state e.g.(fever, rash, conjunctivitis and diarrhea(gastroenteritis). Conclusion MIS-C is a hyper-infammatory syndrome affecting multiple organs especially the heart and is triggered by SARS-CoV-2 infection. It is usually seen 2–4 weeks following infection. In our study,IVIG and steroids might have a beneficial role in MIS-C management.

Acceleration index predicts efficacy of orthostatic training on postural orthostatic tachycardia syndrome in children.

Electrocardiographic acceleration index can be used to predict the effectiveness of orthostatic training in treating children with POTS. • Postural orthostatic tachycardia syndrome (POTS) is a chronic orthostatic intolerance involving multiple mechanisms. Autonomic dysfunction is one of the main mechanisms of POTS in children and could be treated with orthostatic training. • In order to improve the efficacy of orthostatic training in children with POTS, it is particularly important to identify the patients with autonomic dysfunction as the main mechanism before the treatment. • We found acceleration index of the electrocardiogram (ECG) can be used as a satisfactory index to predict the efficacy of orthostatic training in the treatment of POTS in children. • Using the acceleration index to predict the efficacy of orthostatic training on POTS in children is easy to be popularized in hospitals at all levels because it is non-invasive, convenient, and not expensive.

Profiling lipid mediators in serum from children with H1N1 influenza

Influenza A virus subtype H1N1 can cause severe acute respiratory distress syndrome and death in young children and elderly individuals. H1N1 initiates inflammatory responses that aim to contain and eliminate microbial invaders. Various lipid mediators (LMs) are biosynthesized and play a critical role in fighting viruses during inflammation; thus, by profiling the LMs in patients, researchers can obtain mechanistic insights into diseases, such as the pathways disrupted. To date, the relationship between molecular alterations in LMs and the pathogenesis of H1N1 influenza in children is poorly understood. Here, we employed a targeted liquid chromatography coupled with tandem mass spectrometry (LC‒MS/MS) to profile LMs in serum from children with H1N1 influenza (H1N1 children) and recovered children. We found that 22 LM species were altered in H1N1 children with mild symptoms. Analysis of the LM profiles of recovered children revealed a decrease in the levels of thromboxane B2 (TxB2) and thromboxane B3 (TxB3) and an increase in the levels of other 8 altered LM species associated with H1N1 influenza, including cytochrome P450 (CYP) enzyme-derived dihydroxyeicosatrienoic acids (DiHETrEs) and hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid (AA), and epoxyoctadecamonoenoic acids (EpOMEs) from linoleic acid (LA). Taken together, the results of this study revealed that serum LMs change dynamically in H1N1 children with mild symptoms. The dramatically altered LMs in H1N1 children could serve as a basis for potential therapeutics or adjuvants against H1N1 influenza.

The use of pulse transit time in diagnostics of sleep-disordered breathing in children

&lt;b&gt;&lt;br&gt;Introduction:&lt;/b&gt; Sleep is the physiological state of the body where proper morphology and duration are indispensable for human functions throughout both, physical and mental spheres. Disordered breathing during sleep impairs its morphology and results in major disorders in any age group. Adverse effects of Obstructive Sleep Apnea Syndrome in children and poor availability of centers offering children’s polysomnography call for a reliable and easily accessible screening method.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Aim:&lt;/b&gt; The aim of the study were to evaluate the usefulness of pulse transit time in the diagnostics of disordered sleep breathing in children and to attempt to employ the parameter in screening tests. Pulse transit time is a physiological parameter determining the time needed for the pulse wave to travel between two measurement points.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Material and methods:&lt;/b&gt; Enrolled in the retrospective study were 153 patients (100 boys and 53 girls) suspected of obstructive sleep apnea syndrome who underwent polysomnography at I. Mościcki ENT Hospital in Chorzów.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Results:&lt;/b&gt; Statistically significant relations between apnea/hypopnea index and pulse transit time were observed in both, individual age groups and all of the patients. Pulse transit time results proved a negative correlation with apnea/hypopnea index values commonly accepted as a parameter concluding the polysomnography procedures.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Conclusions:&lt;/b&gt; The results of the study indicate that pulse transit time measurements may find application in screening tests of sleep-disordered breathing in children.&lt;/br&gt;

Effect of renal Doppler ultrasound on the detection of nutcracker syndrome in children presenting orthostatic proteinuria

Effect of renal Doppler ultrasound on the detection of nutcracker syndrome in children presenting orthostatic proteinuria

Current Diagnostic and Therapeutic Approaches in May-Thurner Syndrome in Children, Adolescents, and Young Adults: A Survey among Thrombosis Experts of the German Society of Thrombosis and Haemostasis.

May-Thurner syndrome (MTS) is a pelvic venous disorder involving compression of the left common iliac vein by the right common iliac artery, which results in predisposition for deep vein thrombosis. Although MTS is increasingly recognized in young patients, specific guidelines on diagnosis and management for children, adolescents, and young adults do not exist so far. The aim of this study was to assess current diagnostic and therapeutic practice in Germany, Austria, and Switzerland in children and young adults with thrombosis and MTS.We designed an online survey with 11 questions, which we sent via a mailing list to all members of the German, Austrian, and Swiss Society of Thrombosis and Haemostasis Research. Between July and October 2022, 33 specialists answered the questionnaire. Most participating specialists worked at pediatric hospitals (61%). Numbers of annually treated thromboses ranged from <5 (26%) to >30 (13%). Most specialists used venous ultrasound to diagnose deep vein thrombosis, 53% magnetic resonance imaging. Only 25% of specialists systematically screened for MTS in deep vein thrombosis. MTS was managed with anticoagulation (65%), iliac vein stent placement (32%), or balloon angioplasty (13%). In total, 31% of specialists reported to use more than one therapeutic method. Diagnostic and therapeutic approaches for MTS differed between specialists. Lack of standardization resulted in individualized and highly diverse management. Prospective observational clinical studies investigating the outcome of different management strategies including long-term follow-up on outcome and incidence of postthrombotic syndrome will help in defining patient groups who benefit most from revascularizing interventional strategies and developing standardized guidelines.

Metabolic Comorbidities in Pediatric Psoriasis—A Comparative Cross-Sectional Study in South-Asian Children

Abstract Background: There is only limited data on the association between psoriasis and metabolic comorbidities in South-Asian children. Objective: To examine metabolic comorbidities among South-Asian children with and without psoriasis. Materials and Methods: A hospital-based, comparative, cross-sectional study was conducted in children with and without psoriasis over 19 months. Anthropometric, clinical, and metabolic comorbidity details (including disease extent and severity scores, obesity, systemic hypertension, diabetes mellitus, lipid abnormalities, and metabolic syndrome) were obtained in both groups according to standard criteria. Results: Fifty-eight children with psoriasis (25 males/33 females, age 11.3 ± 3.0 years, range 4 to 17 years) and 62 children without psoriasis (37 males/25 females, age 11.0 ± 3.6 years, range 4 to 18 years) were recruited. The prevalence of obesity (31.0% versus 14.5%, P = 0.031, odds ratio 2.65) and metabolic syndrome (18.6% versus 4.6%, P = 0.044, odds ratio 4.68) were higher in children with psoriasis than without. The prevalence of other metabolic comorbidities (systemic hypertension, pre-diabetes, lipid abnormalities, elevated serum alanine aminotransferase, and non-alcoholic fatty liver disease) was not different between children with and without psoriasis and between obese and non-obese children with psoriasis. Among children with psoriasis, those with abdominal obesity had significantly lower disease severity and extent scores than those without. Conclusion: Psoriasis is associated with a significantly higher prevalence of obesity and close to significantly higher prevalence of metabolic syndrome in South-Asian children. Screening for metabolic comorbidities is essential even in non-obese children with psoriasis. Disease extent and severity are less in obese compared to non-obese South-Asian children with psoriasis.

Modulation of innate immunity related genes resulting in prophylactic antimicrobial and antiviral properties

BackgroundThe innate immunity acts during the early phases of infection and its failure in response to a multilayer network of co-infections is cause of immune system dysregulation. Epidemiological SARS-CoV-2 infections data, show that Influenza Virus (FLU-A-B-C) and Respiratory Syncytial Virus (RSV) are co-habiting those respiratory traits. These viruses, especially in children (mostly affected by ‘multi-system inflammatory syndrome in children’ [MIS-C] and the winter pandemic FLU), in the aged population, and in ‘fragile’ patients are causing alteration in immune response. Then, bacterial and fungal pathogens are also co-habiting the upper respiratory traits (e.g., Staphylococcus aureus and Candida albicans), thus contributing to morbidity in those COVID-19 affected patients.MethodsLiquid chromatography coupled with high-resolution mass spectrometry using the quadrupole orbital ion trap analyser (i.e., UHPLC-Q-Orbitrap HRMS) was adopted to measure the polyphenols content of a new nutraceutical formula (Solution-3). Viral infections with SARS-CoV-2 (EG.5), FLU-A and RSV-A viruses (as performed in BLS3 authorised laboratory) and real time RT-PCR (qPCR) assay were used to test the antiviral action of the nutraceutical formula. Dilution susceptibility tests have been used to estimate the minimum inhibitory and bactericidal concentration (MIC and MBC, respectively) of Solution-3 on a variety of microorganisms belonging to Gram positive/ negative bacteria and fungi. Transcriptomic data analyses and functional genomics (i.e., RNAseq and data mining), coupled to qPCR and ELISA assays have been used to investigate the mechanisms of action of the nutraceutical formula on those processes involved in innate immune response.ResultsHere, we have tested the combination of natural products containing higher amounts of polyphenols (i.e., propolis, Verbascum thapsus L., and Thymus vulgaris L.), together with the inorganic long chain polyphosphates ‘polyPs’ with antiviral, antibacterial, and antifungal behaviours, against SARS-CoV-2, FLU-A, RSV-A, Gram positive/ negative bacteria and fungi (i.e., Candida albicans). These components synergistically exert an immunomodulatory action by enhancing those processes involved in innate immune response (e.g., cytokines: IFNγ, TNFα, IL-10, IL-6/12; chemokines: CXCL1; antimicrobial peptides: HBD-2, LL-37; complement system: C3).ConclusionThe prophylactic antimicrobial success of this nutraceutical formula against SARS-CoV-2, FLU-A and RSV-A viruses, together with the common bacteria and fungi co-infections as present in human oral cavity, is expected to be valuable.

МУЛЬТИСИСТЕМНЫЙ ВОСПАЛИТЕЛЬНЫЙ СИНДРОМ, АССОЦИИРОВАННЫЙ С COVID-19 У ДЕТЕЙ, ОСЛОЖНЕННЫЙ ВЕНОЗНЫМИ И АРТЕРИАЛЬНЫМИ ТРОМБОЗАМИ: СЕРИЯ КЛИНИЧЕСКИХ НАБЛЮДЕНИЙ

SARS-CoV-2 causative agent may result in adulthood in hyperinflammatory syndrome and cytokine storm in some patients leading to the microvascular bed thromboses as well as those of large venous and arterial vessels. In the COVID-19 critical form, multisystem inflammatory syndrome in children (MIS-C), thromboses are less common. Authors represent a series of 8 patients’ cases with both thromboses and MIS-C associated with COVID-19 of different localization hospitalized in Nov. 2020-Nov. 2022 aged 4 months to 17 years old (Me 7.5 y/o): 4 aged 4 m/o to 5 y/o and 4 aged 8 to 17 y/o; 6 boys/2 girls. The incidence of thromboses was 13.3% (8/60 pediatric patients with MIS-C); venous thrombosis occurred in 6 (10% of 60), arterial thrombosis in 4 (6.6%), large cerebral vessels thrombosis coupled with the development of bilateral stroke occurred in 2 (3.3%), secondary thrombotic microangiopathy (TMA) in 3 (5%), distal gangrene in a single case (1.7%) and the cerebral venous sinus thrombosis in a single case (1.7%) as well. Treatment was carried out with anticoagulants, aspirin, immunomodulators (intravenous immunoglobulin, glucocorticosteroids, genetically engineered biological drugs). One of 8 patients with thromboses had died from pulmonary embolism (1.7% among all 60 patients with MIS-C), 6 of the 7 survivors continue to be followed up without complications and a single patient continues to have residual severe neurological deficits. Conclusion: venous thrombosis, secondary TMA and large cerebral arteries thrombosis predominated. Treatment of thrombosis with unfractionated heparin intravenously by continuous infusion with a transition to low molecular weight heparins against the background of pathogenetic therapy for MIS-C with immunomodulators was effective in most patients. Acetylsalicylic acid was used in 3 (with coronary dilatation and/or absence of severe thrombocytopenia). Risk factors for thromboses were male gender, severe congenital underlying diseases.

Inflammatory and Autoimmune Aspects of Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Cohort Study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate-severe COVID-19 (COVID+) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID+ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID+ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID+ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID+ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation.

Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity

Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

Is there an overestimation of dengue compared with that of other acute febrile syndromes in childhood?

Is there an overestimation of dengue compared with that of other acute febrile syndromes in childhood?

Updates on postinfectious skin rashes in pediatric dermatology.

This review provides updates on postinfectious skin rashes in the pediatric population from recently published literature. The COVID-19 pandemic and its sequelae remain a focus of research on pediatric infectious skin rashes. Multisystem inflammatory syndrome in children (MIS-C) and reactive infectious mucocutaneous eruption (RIME) are common complications of infection with SARS-COV-2 in the pediatric population. Most cases of MIS-C show low mortality and suggest mucocutaneous symptoms do not correlate with COVID-19 disease severity. Cases of papular acrodermatitis of childhood, also known as Gianotti-Crosti, have also been reported in association with SARS-COV-2, and can present similarly in reaction to other viral infection like molluscum contagiosum, known as a Gianotti-Crosti syndrome-like reaction (GCLR). Other relevant studies on postinfectious skin rashes include updates on the management of staphylococcal scalded skin syndrome (SSSS), with newer evidence advocating for beta-lactam monotherapy without clindamycin and reduced ancillary testing. Finally, the emergence of antifungal resistance due to Trichophyton indotinae is a growing global health concern emphasizing the need for improved antifungal stewardship. It is prudent for clinicians to be informed of both common and rare diagnoses that have emerged more recently in association with the COVID-19 pandemic, in addition to other diseases with newer evidence-based recommendations to guide management.

Proteomic profiling reveals diagnostic signatures and pathogenic insights in multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that emerged during the COVID-19 pandemic. Although recognized as an immune-mediated condition, the pathogenesis remains unresolved. Furthermore, the absence of a diagnostic test can lead to delayed immunotherapy. Using state-of-the-art mass-spectrometry proteomics, assisted by artificial intelligence (AI), we aimed to identify a diagnostic signature for MIS-C and to gain insights into disease mechanisms. We identified a highly specific 4-protein diagnostic signature in children with MIS-C. Furthermore, we identified seven clusters that differed between MIS-C and controls, indicating an interplay between apolipoproteins, immune response proteins, coagulation factors, platelet function, and the complement cascade. These intricate protein patterns indicated MIS-C as an immunometabolic condition with global hypercoagulability. Our findings emphasize the potential of AI-assisted proteomics as a powerful and unbiased tool for assessing disease pathogenesis and suggesting avenues for future interventions and impact on pediatric disease trajectories through early diagnosis.

The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C

ObjectivesThe aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. Study designMulticenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1–4, 5–11, 12–16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. ResultsTime to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. ConclusionsThe stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.