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Introduction . This study aims to describe the clinical and paraclinical characteristics of Multisysteminflammatory syndrome in children (MIS-C).  Methods . A retrospective study encompassing 52 children diagnosed with MIS-C according to the World Health Organization criteria, over a 3-year period at Abderrahim Harrouchi Hospital in Morocco.  Results . The median age was 6 years (IQR: 1-14), with a sex ratio of 1.16 (28 boys and 24 girls). Clinical manifestations were predominantly characterized by fever in all cases (100%), respiratory and gastrointestinal symptoms in 30 cases (58%) and 23 cases (44%) respectively, and shock in 9 cases (17%). We noted a myocarditis in 6 cases (12%). The treatment comprised intravenous human Immunoglobulin combined with methylprednisolone in all patients (100%).  Conclusion . The characteristics of our MIS-C patients were similar to those in the literature, but more studies are needed to confirm these results., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Introduction: Hyper-IgE syndrome is a group of inborn errors of immunity, some of which are syndromic, characterized clinically by the classic triad of chronic eczema, cutaneous and/or pulmonary staphylococcal infections and high serum IgE concentrations (> 2000 IU/ml or > 10 x normal for age)., Aim: We report here the clinical and immunological aspects of Moroccan patients presenting probable or possible HIES according to NIH-HIES score., Methods: This retrospective study covers the period from 1998 to 2023 and includes Moroccan patients with a clinical presentation suggestive of HIES (skin and/or pulmonary infections, eczema, high IgE levels) and an NIH score ≥ 20. We attempted to classify the patients phenotypically according to the 2022 IUIS IEI Expert Committee classification., Results: Median age at symptom onset was 0.5 years and median age at diagnosis was 5.5 years. The main clinical signs were eczema (66%), skin abscesses (32.5%), pneumonia (32.5%), otitis (20%), mucocutaneous candidiasis (19%), diarrhea (12%), facial dysmorphism (10.3%), lymphadenopathy (9.5%), bronchial dilation (8%), pneumatoceles (8%), conjunctivitis (7.1%), rhinitis (6.3%), psychomotor delay (5.6%), pathological fractures (4%), retention of deciduous teeth (4%), cognitive delay (3.2%)., Conclusion: This is the first clinical description of a cohort of Moroccan patients presenting HIES according to NIH criteria. Phenotype can sometimes orient towards identification of the mutated gene, but the overlapping clinical signs make molecular analysis necessary for genetic counseling and appropriate treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces pneumonia and acute respiratory failure in Coronavirus Disease 2019 (COVID-19) patients with inborn errors of immunity to type I interferon (IFN-I). The impact of SARS-CoV-2 infection varies widely, ranging from mild respiratory symptoms to life-threatening illness and organ failure, with a higher incidence in men than in women. Approximately 3 to 5% of critical COVID-19 patients under 60 and a smaller percentage of elderly patients exhibit genetic defects in IFN-I production, including X-chromosome-linked TLR7 and autosomal TLR3 deficiencies. Around 15 to 20% of cases over 70 years old, and a smaller percentage of younger patients, present with preexisting autoantibodies neutralizing type I interferons. Additionally, innate errors affecting the control of the response to type I interferon have been associated with pediatric multisystem inflammatory syndrome (MIS-C). Several studies have described rare errors of immunity, such as XIAP deficiency, CYBB, SOCS1, OAS1/2, and RNASEL, as underlying factors in MIS-C susceptibility. However, further investigations in expanded patient cohorts are needed to validate these findings and pave the way for new genetic approaches to MIS-C. This review aims to present recent evidence from the scientific literature on genetic and immunological abnormalities predisposing individuals to critical SARS-CoV-2 infection through IFN-I. We will also discuss multisystem inflammatory syndrome in children (MIS-C). Understanding the immunological mechanisms and pathogenesis of severe COVID-19 may inform personalized patient care and population protection strategies against future serious viral infections., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Morocco has made remarkable progress in the fight against tuberculosis, but the Covid-19 pandemic has affected tuberculosis control worldwide, with notable fluctuations in tuberculosis epidemiology during and after the pandemic., Aim: To describe the impact of the Covid-19 pandemic on the rate of hospitalization for tuberculosis and its different localizations in children., Methods: We conducted a retrospective study based on the analysis of medical records of TB patients hospitalized within the Children's Hospital in Casablanca, during the periods before (2018-2019), during (2020) and after (2021-2022) Covid-19 quarantine., Results: Throughout the study period (2018-2022), the total number of patients hospitalized in our department was 7390, including 283 children were hospitalized for tuberculosis, with a mean age of 6 years. Before the Covid-19 pandemic, the average number of tuberculosis cases was 49 per year, of which the percentage of pulmonary tuberculosis was 32% and extra-pulmonary tuberculosis 68%. The number of cases was 23 per year during the quarantine period, with a percentage of pulmonary tuberculosis of 26% and extra-pulmonary tuberculosis of 74%. After the quarantine period, this number rose to 81 cases per year, of which 21% were pulmonary tuberculosis and 79% extrapulmonary tuberculosis (pleural tuberculosis was predominant in 44.1% of cases)., Conclusion: These results are consistent with data published by the World Health Organization, and with the findings of another study we carried out on the impact of COVID-19 on hospital admissions for acute lower respiratory tract infections. It is very likely that the reduction in the number of tuberculosis cases during the quarantine period is due to social distancing, which leads to a reduction in the transmission of tuberculosis between people as well as to the disruption of the national tuberculosis control program in Morocco, when positive cases are identified.

It is estimated that in highly medicalised countries, median life expectancy for most newborns with cystic fibrosis now exceeds 70 years, approaching that of the general population. However, socio-economic disparities between countries continue to have a devastating impact on the prognosis of patients in Eastern Europe, Africa, India and South America. In Morocco, very limited genetic data suggest that the prevalence of this disease is at least of the same order as in Belgium. But as it is not really recognised by the national health system, patients are denied access even to symptomatic treatment. As a result, their outcome is tragic, similar to what it was 60 years ago in the most medicalised countries. A pilot project for a first paediatric reference centre in Casablanca is currently being set up. If properly resourced, this project can only be a success and should be the first step on the road towards cystic fibrosis care in this country. In a very humble way, several Belgian stakeholders are trying to support this project.

Purpose: Genetic testing provides great support to validate the clinical diagnosis of inborn errors of immunity (IEI). However, the high cost and advanced technology make these tests inaccessible to a large proportion of patients in low-income countries. In the present study, we aim to evaluate the Moroccan experience in genetic testing and to report the main molecular features and difficulties encountered in genetic diagnosis., Methods: We performed a multi-center retrospective analysis of all patients with a molecular diagnosis and registered in the national registry between 2010 and 2022. To estimate the impact of the newly identified mutations, we calculated the Combined Annotation Dependent Depletion (CADD) score and the mutation significance cutoff (MSC) for each variant., Results: A total of 216 (29%) patients received a genetic diagnosis out of 742 patients with IEI included in the registry. All genetic tests were performed in the context of thesis projects (40%) or international collaborations (60%). A set of 55 genetic defects were identified, including 7 newly reported: SNORA31, TBX21, SPPL2A, TYK2, RLTPR, ZNF341, and STAT2 GOF. Genetic diagnoses were more frequent in the defects of innate and intrinsic immunity with a percentage of 78%, while antibody deficiencies had a lower frequency with a percentage of 17.5%. Only one genetic diagnosis has been made in the complement deficiency group. The most commonly used molecular techniques were Sanger sequencing (37%) followed by targeted gene sequencing (31%)., Conclusion: The thesis projects and collaborations were beneficial as they allowed us to provide a definitive genetic diagnosis to 29% of the patients and to contribute to the identification of new genetic defects and mutations. These results offer insight into the progress made in genetic diagnoses of IEI in Morocco, which would provide a baseline for improving the clinical management of patients with IEI., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Severe combined immunodeficiency (SCID) is a heterogeneous group of primary immunodeficiency diseases (PIDs) characterized by a lack of autologous T lymphocytes. This severe PID is rare, but has a higher prevalence in populations with high rates of consanguinity. The epidemiological, clinical, and immunological features of SCIDs in Moroccan patients have never been reported. The aim of this study was to provide a clinical and immunological description of SCID in Morocco and to assess changes in the care of SCID patients over time. This cross-sectional retrospective study included 96 Moroccan patients referred to the national PID reference center at Casablanca Children's Hospital for SCID over two decades, from 1998 to 2019. The case definition for this study was age < 2 years, with a clinical phenotype suggestive of SCID, and lymphopenia, with very low numbers of autologous T cells, according to the IUIS Inborn Errors of Immunity classification. Our sample included 50 male patients, and 66% of the patients were born to consanguineous parents. The median age at onset and diagnosis were 3.3 and 6.5 months, respectively. The clinical manifestations commonly observed in these patients were recurrent respiratory tract infection (82%), chronic diarrhea (69%), oral candidiasis (61%), and failure to thrive (65%). The distribution of SCID phenotypes was as follows: T-B-NK+ in 44.5%, T-B-NK- in 32%, T-B+NK- in 18.5%, and T-B+NK+ in 5%. An Omenn syndrome phenotype was observed in 15 patients. SCID was fatal in 84% in the patients in our cohort, due to the difficulties involved in obtaining urgent access to hematopoietic stem cell transplantation, which, nevertheless, saved 16% of the patients. The autosomal recessive forms of the clinical and immunological phenotypes of SCID, including the T-B-NK+ phenotype in particular, were more frequent than those in Western countries. A marked improvement in the early detection of SCID cases over the last decade was noted. Despite recent progress in SCID diagnosis, additional efforts are required, for genetic confirmation and particularly for HSCT.

Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is typically sporadic. Inborn errors of TLR3- and DBR1-mediated central nervous system cell-intrinsic immunity can account for forebrain and brainstem HSE, respectively. We report five unrelated patients with forebrain HSE, each heterozygous for one of four rare variants of SNORA31, encoding a small nucleolar RNA of the H/ACA class that are predicted to direct the isomerization of uridine residues to pseudouridine in small nuclear RNA and ribosomal RNA. We show that CRISPR/Cas9-introduced bi- and monoallelic SNORA31 deletions render human pluripotent stem cell (hPSC)-derived cortical neurons susceptible to HSV-1. Accordingly, SNORA31-mutated patient hPSC-derived cortical neurons are susceptible to HSV-1, like those from TLR3- or STAT1-deficient patients. Exogenous interferon (IFN)-β renders SNORA31- and TLR3- but not STAT1-mutated neurons resistant to HSV-1. Finally, transcriptome analysis of SNORA31-mutated neurons revealed normal responses to TLR3 and IFN-α/β stimulation but abnormal responses to HSV-1. Human SNORA31 thus controls central nervous system neuron-intrinsic immunity to HSV-1 by a distinctive mechanism.