Longitudinal cytokine profile in severe COVID-19 and multisystem inflammatory syndrome in children: A single centre study from Egypt.

Aim: The severity of COVID-19 is influenced by uncontrolled hyper-inflammatory response with excessive release of many cytokines and chemokines. The understanding of the temporal change in the cytokine levels that underlies the diverse clinical presentations of COVID-19 can help in the prediction of the disease outcome and in the design of proper treatment strategies.

Method: Data were collected from children (<18 years old) hospitalised with severe COVID-19 or severe MIS-C who were compared to a group of healthy control children.

The epigenetic determinants for systemic juvenile idiopathic arthritis phenotyping and treatment response.

Background: Determining the role of epigenetics in systemic juvenile idiopathic arthritis (SJIA) provides an opportunity to explore previously unrecognized disease pathways and new therapeutic targets.

Aim: We aimed to identify the clinical significance of microRNAs (miRNA-26a, miRNA-223) in SJIA.

Materials And Methods: This cross-sectional study was conducted on a group of children with SJIA attending to pediatric rheumatology clinic, at Mansoura University Children's Hospital (MUCH) from December 2021 to November 2022.

SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis.

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

Objectives: The 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 Design: Multicenter 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.

Genetic association of ACE2 and TMPRSS2 polymorphisms with COVID-19 severity; a single centre study from Egypt.

Background: Since the emergence of the COVID-19 infection in China, it has caused considerable morbidity, mortality, and economic burden. It causes the vast majority of clinical manifestations, ranging from mild or even no symptoms to severe respiratory failure. There are many risk factors for severe COVID-19, such as old age, male gender, and associated comorbidities.

Regulatory T-cell dysfunction and cutaneous exposure to Staphylococcus aureus underlie eczema in DOCK8 deficiency.

Background: Dedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD).

Objective: We sought to understand the mechanisms of eczema in DOCK8 deficiency.

Methods: Skin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression.

Clinical and Immunological Impacts of Latent Toxoplasmosis on COVID-19 Patients.

Background Parasites are well-known immune-modulators. They inhibit some aspects of the immune system to ensure persistence inside the host for a long time; meanwhile, they stimulate other immune aspects to assure the survival of the host. Wide variations in the severity of coronavirus disease 2019 (COVID-19) among developed and developing countries were reported during the COVID-19 pandemic.

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.

Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia.

Offset Acetabular Liners: Safer Than Previously Thought.

High offset liners help to restore soft tissue tension after primary total hip arthroplasty (THA). However, prior research has reported increased rates of aseptic loosening when using offset components. The purpose of this study was to examine the postoperative complication and revision rates of neutral vs offset acetabular liners at our institution.

How multisystem inflammatory syndrome in children discriminated from Kawasaki disease: a differentiating score based on an inception cohort study.

Background: About 25-50% of multisystem inflammatory syndrome in children (MIS-C) patients meet the criteria for diagnosis of Kawasaki disease (KD). The differentiation of both conditions is so challenging on clinical practice as the management of both is time dependant and precise diagnosis is fundamental.

Method: Data were collected from children < 18 years old hospitalized with MIS-C or KD.

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.

Background: We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.

Methods: We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.

The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity.

Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders.

COVID-19 diversity: A case of multisystem inflammatory syndrome in children masquerading as juvenile systemic lupus erythematosus.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may present with some systemic lupus erythematosus (SLE) manifestations intermingled with Kawasaki disease features. These emerging presentations were dubbed under the umbrella term 'multisystem inflammatory syndrome in children (MIS-C)'. A one and half-year-old girl, admitted to Mansoura University Children's Hospital (MUCH) with fever, bad general condition, vomiting, widespread maculopapular, vasculitic rash, hands and feet oedema, oral ulceration, arthralgia and lymphadenopathy.

Clinical, immunological, molecular and therapeutic findings in monogenic immune dysregulation diseases: Middle East and North Africa registry.

Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated.

Thoracic Fluid Content in Neonates Presented with Respiratory Distress as a Predictive Tool for Transient Tachypnea of Newborn.

Introduction: Respiratory conditions are the most common reason for admission of newborns to a neonatal care unit. The index of contractility (ICON) can be used to measure the thoracic fluid content (TFC) in neonates which is a significant parameter in cases presented with transient tachypnea of newborn (TTN).

Objective: The objective was to compare TFC between newborn infants with TTN compared with other causes of respiratory distress (RD).

Early predictors of colchicine resistance in familial Mediterranean fever.

Objective: To explore early features that can predict colchicine resistance in familial Mediterranean fever (FMF) patients.

Methods: It included FMF cases who fulfilled the Yalcinkaya-Ozen criterion and were on colchicine for at least 6 months. Data were collected from medical files and interpreted with respect to clinical parameters, incluing the auto-inflammatory diseases activity index (AIDAI) and FMF severity score.

Digenic inheritance of IL-36RA and SEC61A1 mutations underlies generalized pustular psoriasis with hypogammaglobulinemia.

We report a female patient presenting with generalized pustular psoriasis and hypogammaglobulinemia due to digenic mutations in IL-36RA and SEC61A1. The patient presented with recurrent fevers, elevated inflammatory markers, hepatosplenomegaly, and recurrent sinopulmonary infections in the context of hypogammaglobulinemia which improved on immunoglobulin replacement. This report demonstrates how digenic inheritance leads to complex phenotypes, and illustrates the importance of following an unbiased approach to identifying variants, especially in patients with atypical clinical presentations.

Physicians' knowledge and practice concerning diagnosis and management of anaphylaxis: The situation in Egypt.

Introduction: Early recognition of an anaphylaxis event is crucial for instituting lifesaving management. We sought to explore knowledge and practice towards anaphylaxis in a sample of physicians from ten Egyptian governorates.

Methods: An eighteen question-based questionnaire was developed by expert allergists to evaluate the knowledge and practice towards anaphylaxis, based on the World Allergy Organization guidelines for the assessment and management of anaphylaxis.

Cardiac implications of multisystem inflammatory syndrome associated with COVID-19 in children under the age of 5 years.

Background: Coronavirus disease 2019 (COVID-19) is responsible for significant lung disease in adults. Despite mild manifestations in most children, multisystem inflammatory syndrome (MIS-C) associated with COVID-19 is well described in older children with cardiac manifestations. However, MIS-C-related cardiac manifestations are not as well described in younger children.

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity.

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis.

Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region.