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The SARS-CoV-2 pandemic has led to over 4.9 million deaths as of October 2021. One of the main challenges of creating vaccines, treatment, or diagnostic tools for the virus is its mutations and emerging variants. A couple of variants were declared as more virulent and infectious than others. Some approaches were used as nomenclature for SARS-CoV-2 variants and lineages. One of the most used is the Pangolin nomenclature. In our study, we enrolled 35 confirmed SARS-CoV-2 patients and sequenced the viral RNA in their samples. We also aimed to highlight the hallmark mutations in the most frequent lineage. We identified a seven-mutation signature for the SARS-CoV-2 C36 lineage, detected in 56 countries and an emerging lineage in Egypt. In addition, we identified one mutation which was highly negatively correlated with the lineage. On the other hand, we found no significant correlation between our clinical outcomes and the C36 lineage. In conclusion, the C36 lineage is an emerging SARS-CoV-2 variant that needs more investigation regarding its clinical outcomes compared to other strains. Our study paves the way for easier diagnosis of variants of concern using mutation signatures.

Background: Persistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators, including lipoxins that regulate airway inflammation. Mutations at various positions in ALOX-15 gene can influence airway disease development. We investigated association between ALOX-15,c.-292 C > T gene polymorphism and bronchiectasis unrelated to cystic fibrosis in Egyptian children. Also, lipoxin A4 (LXA4) level in bronchoalveolar lavage (BAL) was studied in relation to polymorphism genotypes and disease phenotypes determined by clinical, pulmonary functions, and radiological severity parameters., Methods: This was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method., Results: There was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53-5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6-1510) ng/ml compared to controls, median (IQR) of 1675 (536.8-2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005)., Conclusions: Low airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production., (© 2024. The Author(s).)

Background: COVID-19 leads to severe overwhelming inflammation in some patients mediated by various cytokines (cytokine storm) that usually leads to severe illness accompanied by cardiovascular manifestations. Growth differentiation factor-15 is a cytokine induced by stress and is associated with inflammatory processes in the lung and heart. This study aimed to measure the level of serum growth differentiation factor (GDF-15) in children with COVID-19 and to correlate it with the disease severity, cardiac affection, and the outcome of COVID-19., Methods: A cross-sectional study was conducted on 144 children; 72 children diagnosed with COVID-19, and 72 healthy children. The severity of COVID-19 was assessed clinically, laboratory, and radiologically. Echocardiography was done within 48 h of admission for COVID-19 patients. Serum GDF-15 was measured by ELISA for both patients and controls., Results: Serum GDF-15 level was significantly higher in patients with COVID-19 than in controls (p < 0.01). In COVID-19 patients with severe clinical grading, those who were hospitalized in the PICU, and those who died, serum GDF-15 levels were greater. individuals with cardiac manifestations exhibited significantly higher serum GDF-15 levels than individuals without them. In children with COVID-19, increased GDF-15 was correlated to poorer ejection fraction and higher INR using multivariate linear regression analysis., Conclusion: Serum GDF-15 is a promising biomarker of COVID-19, it can be used as a predictor of cardiac manifestations in children with COVID-19 and severe disease., (© 2023. The Author(s).)

Background: Thrombosis and embolism are possible complications in coronavirus disease 2019 (COVID)-19-positive pediatric patients. Although the risk is lesser in children than it is in adults, it does exist during acute infection and multi-inflammatory syndrome in children. Biomarkers such asd-dimer, prothrombin time, and fibrinogen degradation products are ineffective at detecting disease severity. Homocysteine (Hcy) is a prothrombotic factor that has been reported to be higher in adult COVID-19 patients, leading to speculation that it could be used as a biomarker for disease severity., Purpose: To detect the correlation between serum total homocysteine (tHcy) level and the severity of COVID-19 in pediatrics., Methods: A cross-sectional study was conducted on 40 children with COVID-19 and 40 healthy control subjects. Serum tHcy was measured by enzyme-linked immunosorbent assay and correlated with the clinical, laboratory, and radiological parameters of the patients., Results: The median serum tHcy level in COVID-19 patients was 27.5 (interquartile range [IQR]: 23-31.75) μmol/L, while that in the controls was 1.8 (IQR: 1.6-1.875) μmol/L. There was a statistically significant increase in the tHcy level in cases compared to controls (p < 0.001). There was a statistically significant positive correlation between serum tHcy and d-dimer, ferritin, alanine transaminase, aspartate transaminase, blood urea nitrogen, and a highly significant positive correlation between tHcy and COVID-19 reporting and data system score, pediatric intensive care unit admission, and the disease severity classification., Conclusion: Hcy could be a biomarker of importance in predicting the severity of COVID-19 in pediatrics., (© 2022 Wiley Periodicals LLC.)

Background and Aims: Sputum neutrophil elastase (NE) is a marker of neutrophilic airway inflammation in bronchiectasis. Yet, not much is known about its role in pediatric bronchiectasis severity. This study aimed to assess the sputum NE value as a biomarker of clinical and radiological severity in pediatric bronchiectasis., Methods: This was a cross-sectional study assessing sputum NE in a total of 50 bronchiectasis patients under the age of 18 years-30 patients with cystic fibrosis (CF) and 20 patients with non-CF bronchiectasis were included. Bronchiectasis severity was assessed using Shwachman-Kulczycki (SK) score, CF-ABLE score, and CF risk of disease progression score, among CF patients, and bronchiectasis severity index (BSI) and FACED criteria among non-CF bronchiectasis patients, associations between sputum NE and bronchiectasis severity were assessed in both patient groups., Results: Sputum NE was directly correlated with C-reactive protein ( r  = 0.914, p  < 0.001), ( r  = 0.786, p  < 0.001), frequency of exacerbations ( r  = 0.852, p  < 0.001) ( r  = 0.858, p  < 0.001), exacerbations severity ( r  = 0.735, p  = 0.002), ( r  = 0.907, p  < 0.001), and the number of hospital admissions ( r  = 0.813, p  < 0.001), ( r  = 0.612, p  = 0.004) in the last year among CF, and non-CF bronchiectasis patients, respectively. Additional linear correlations were found between sputum NE, CF risk of disease progression score ( p  < 0.001), CF-ABLE score ( p  < 0.001), and lower forced expiratory volume 1% of predicted ( p  = 0.017; ρ  = -0.8) among CF patients. Moreover, sputum NE was positively correlated with the neutrophil count ( p  = 0.018), and BSI severity score ( p = 0.039; ρ  = 0.465) among non-CF bronchiectasis patients., Conclusions: Sputum NE may be considered a good biomarker of bronchiectasis severity in both CF and non-CF bronchiectasis patients, as confirmed by the exacerbations rate, CF risk of disease progression, and BSI scores., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Objective: To report and describe cases of children presenting with coronavirus disease 2019 (COVID-19)-related multisystem inflammatory syndrome in children (MIS-C) with new-onset type 1 diabetes mellitus (T1DM) in severe diabetic ketoacidosis (DKA)., Research Design and Methods: This prospective observational study was conducted to characterize children with COVID-19-related MIS-C and new-onset T1DM who were in DKA. MIS-C was diagnosed if Centers for Disease Control and Prevention and World Health Organization criteria were fulfilled., Results: Six cases were identified. The patients were critically ill and in nonfluid responsive shock (combined hypovolemic and cardiogenic or distributive shock). All had cardiac involvement. One patient had a Kawasaki shock-like presentation. All needed aggressive treatment with careful monitoring of fluid balance (because of associated cardiac dysfunction), early institution of vasoactive/inotropic supports, and use of methylprednisolone and intravenous immunoglobulins. The latter are better administered after DKA resolution to avoid undue volume overload and fluid shifts while the patients are in DKA., Conclusions: Awareness of MIS-C coexistence with DKA at T1DM onset is crucial for rapid proper management., (© 2022 by the American Diabetes Association.)

Background: Childhood interstitial and diffuse lung diseases (chILD) encompass a broad spectrum of rare pulmonary disorders. In most developing Middle Eastern countries, chILD is still underdiagnosed. Our objective was to describe and investigate patients diagnosed with chILD in a tertiary university hospital in Egypt., Methods: We analysed data of consecutive subjects (aged <18 years) referred for further evaluation at the Children's Hospital, Ain Shams University (Cairo, Egypt). Diagnosis of chILD was made in accordance with the ChILD-EU criteria. The following information was obtained: demographic data, clinical characteristics, chest computed tomography findings, laboratory studies, spirometry, bronchoalveolar lavage and histopathology findings., Results: 22 subjects were enrolled over 24 months. Median age at diagnosis was 7 years (range 3.5-14 years). The most common manifestations were dyspnoea (100%), cough (90.9%), clubbing (95.5%) and tachypnoea (90.9%). Systematic evaluation led to the following diagnoses: hypersensitivity pneumonitis (n=3), idiopathic interstitial pneumonias (n=4), chILD related to chronic granulomatous disease (n=3), chILD related to small airways disease (n=3), post-infectious chILD (n=2), Langerhans cell histiocytosis (n=2), idiopathic pulmonary haemosiderosis (n=2), granulomatous lymphocytic interstitial lung disease (n=1), systemic sclerosis (n=1) and familial interstitial lung disease (n=1). Among the subjects who completed the diagnostic evaluation (n=19), treatment was changed in 13 (68.4%) subjects., Conclusion: Systematic evaluation and multidisciplinary peer review of chILD patients at our tertiary hospital led to changes in management in 68% of the patients. This study highlights the need for an Egyptian chILD network with genetic testing, as well as the value of collaborating with international groups in improving healthcare for children with chILD., Competing Interests: Conflict of interest: S.G. Abdelhady has nothing to disclose. Conflict of interest: E.M. Fouda has nothing to disclose. Conflict of interest: M.A. Shaheen has nothing to disclose. Conflict of interest: F.A. Ghazal has nothing to disclose. Conflict of interest: A.M. Mostafa has nothing to disclose. Conflict of interest: A.M. Osman has nothing to disclose. Conflict of interest: A.G. Nicholson reports personal fees for consultancy on idiopathic pulmonary fibrosis (IPF) trials and education from Boehringer Ingelheim, and personal fees for consultancy on IPF trials from Medical Quantitative Image Analysis and Galapagos, outside the submitted work. Conflict of interest: H.M. Hamza has nothing to disclose., (Copyright ©The authors 2021.)

The global concern of increasing number of children presenting with multisystem inflammatory syndrome in children (MIS-C) related to the coronavirus disease (COVID-19) has escalated the need for a case-oriented clinical approach that provides timely diagnosis and management. The aim of this study is to share our experience in managing 64 MIS-C patients of North African ethnicity guided by a risk-based algorithm. Sixty-four patients met the inclusion criteria, 19 (30%) patients were categorized as mild and moderate risk groups and cared for in an isolation ward and 45 patients who belonged to the high-risk group (70%) were admitted to the pediatric intensive care unit (PICU). Positive laboratory evidence of COVID-19 was found in 62 patients. Fever and dysfunction in 2 or more organs were confirmed in all cases (100%). Fifty patients (78%) presented with gastrointestinal symptoms, meanwhile only 10 patients (16%) had respiratory manifestations. Cardiac involvement was reported in 55 (86%) cases; hypotension and shock were found in 45 patients (70%) therein circulatory support and mechanical ventilations were needed for 45 and 13 patients respectively. Intravenous immunoglobulins (IVIG) were used for all cases and methylprednisolone was used in 60 patients (94%). Fifty-eight (91%) patients were discharged home after an average of 9 days of hospitalization. The mortality rate was 9% (6 patients). Conclusion . A single Egyptian center experience in the management of MIS-C patients guided by a proposed bed side algorithm is described. The algorithm proved to be a helpful tool for first-line responders, and helped initiate early treatment with IVIG., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: This study's aim is to evaluate lung ultrasound (LUS) efficacy in detecting opening and closing lung pressures and its correlation with the tracheal interleukin 6 (IL-6) level., Method: This single-blinded randomized controlled study was done at Ain Shams University Children's Hospital neonatal intensive care units, Egypt. It consists of 44 mechanically ventilated preterm neonates with Respiratory Distress Syndrome (RDS). Initial LUS assessment was done followed by randomization to one of 2 groups; group I: 22 patients underwent LUS guided RM and group II: 22 patients underwent non-ultrasound guided RM. Tracheal IL-6 level was measured before and after RM in both groups., Results: The LUS scores showed a sensitivity of 86.7%, specificity of 62.10% and accuracy of 70.45% at the cut-off point >B1 grade. After RM, there was a higher percentage of changes in mean airway pressure (p = 0.03), FiO2 (p = 0.01), PaO2/FiO2 ratio (p = 0.01), and IL-6 (p < 0.01) in group I. The duration of oxygen requirement (6 vs.13.5 days, p = 0.01), invasive ventilation (3 vs.5.5 days, p = 0.03), non-invasive ventilation (2.5 vs. 5 days, p = 0.02) and NICU stay (21.5 vs. 42.5 days, p = 0.03) were less in group I. A positive correlation is found between reaeration score and the duration of O2 requirement (p = 0.002), duration of invasive ventilation (p = 0.001), NICU length of stay (p = 0.002) and negative correlation with PaO2/FiO2 ratio before RM (p = 0.012). The best cut-off point for the reaeration score is >21 with a sensitivity of 75%, specificity of 71.43% and area under the curve of 78.1%., Conclusion: LUS-guided RM achieved earlier lowest FiO2, shorter O2 dependency, lesser NICU stay and marked decrease in lung inflammation by decreasing atelectotrauma and shortening the duration of invasive ventilation.

Background: In recent years, the prevalence of asthma has risen in developed countries, and its extent related to a change in our indigenous microbiota. Helicobacter pylori disappearance across the population represents a fundamental change in our human microbiota and has preceded the rise in asthma prevalence., Objective: To assess the relationship between childhood asthma and Helicobacter pylori infection., Methods: Quantitative determination of Helicobacter pylori IgG among 90 asthmatic children and 90 - age and gender - matched non-atopic, non-asthmatic healthy children was performed using ELISA in serum of all participants., Results: Helicobacter pylori IgG seropositivity was found in 25.6% of asthmatics compared to 44.4% of controls. Asthmatics showed lower median Helicobacter pylori IgG titre compared to healthy controls. We also detected a significant inverse relationship between Helicobacter pylori IgG titre and asthma severity., Conclusion: Helicobacter pylori seropositivity protects against childhood asthma and inversely correlates to its clinical and functional severity., (Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: While recognizing the etiology of community-acquired pneumonia is necessary for formulating local antimicrobial guidelines, limited data is published about this etiology in Egyptian pediatric patients., Objectives: To determine the frequency of bacterial and viral pathogens causing community-acquired pneumonia (CAP) among immunocompetent Egyptian infants and preschool children., Methods: Ninety infants and preschool-age children admitted to our hospital with CAP were prospectively included in the study. Etiological agents were identified using conventional bacteriological identification methods and IgM antibodies detection against common atypical respiratory bacteria and viruses., Results: An etiology was identified in 59 patients (65.5%). Bacterial pathogens were detected in 43 (47.8%) of the cases while viral pathogens were detected in 23 (25.5%). Coinfection with more than one etiologic agent was evident in seven patients (7.8%). The most common typical bacterial cause of pneumonia was Staphylococcus aureus ( n = 12, 13.3%), followed by Streptococcus pneumoniae and Klebsiella pneumoniae ( n = 7, 7.8%, each). The commonest atypical bacterium was Mycoplasma pneumoniae ( n = 10, 11.1%), whereas the commonest viral etiology was influenza viruses ( n = 11, 12.2%)., Conclusion: Although we could not determine the causative agent in some studied cases, this study provides preliminary data regarding the spectrum and frequency of microorganisms causing CAP in Egyptian infants and preschool children., Competing Interests: The authors declare no conflict of interest.