Multisystem inflammatory syndrome in children (MIS-C) is a disease that made its mark in the early days of the COVID-19 pandemic due to the diverse course and symptoms affecting multiple body systems. It is a condition that develops in pediatric patients about 2-6 weeks after contact with a person infected with the SARS-CoV-2 virus. In many instances, MIS-C has caused multiple organ failure, with particularly severe complications involving the cardiovascular system and manifesting as hypotension, various cardiac arrhythmias, myocarditis or coronary artery lesions resembling those seen in Kawasaki disease. Currently, the incidence of MIS-C is about 1-3 per 1000 children, with a decreasing trend in recent years due to the introduction of immunization against the SARS-CoV-2 virus for children as young as 6 months. In our paper, we present the case of a patient with a severe course of MIS-C with numerous cardiovascular and neurological complications, in whom the symptoms of the disease were managed by administering biological treatment. We also present a review of the literature on the subject, which shows how many different facets this disease can have and that physicians still need to remain alert, as there are cases of severe MIS-C, especially in unvaccinated patients.

To evaluate giant aneurysms (GiAn) prevalence in Arab countries and examine contributing factors; and to review Kawasaki disease (KD) publication trends and collaborations among Arab nations. A scoping literature review was conducted to analyze the publications across the Arab world, spanning 16 countries from 1978 to 2023. The collected articles were a combination of database search with a call on Kawasaki Disease Arab Initiative (Kawarabi) members to share non-PubMed publications. Over 45 years, 50 articles originated from the Arab Countries with a 30% average annual growth rate in KD research output. Publications were evenly split between case reports (42%) and institutional series (52%). Research productivity lagged in developing nations with UAE, KSA and Egypt, contributed to 64% of total publications. Among 26 institutional series, 256 coronary artery aneurysms (CAA) from a total of 1264 KD cases were reported. Of those, 25 CAA were GiAn (prevalence 1.43% [range 0-12.5%]). The initial KD misdiagnosis rate was 4%, and incomplete KD (iKD) averaged 10.6%. Series (38.5%) that did not report iKD correlated with a higher prevalence of CAA, but not of GiAn. Longer fever duration emerged as a pivotal factor for GiAn (OR 5.06, 95%CI 1.51-17). This review unveils the research landscape of KD in the Arab world over 45 years. Initial misdiagnosis, untreated cases, delayed diagnosis and underreporting of iKD are contributing factors for an underestimated epidemiology, explaining the higher GiAn prevalence. This calls for strategic interventions to enhance KD research in these countries, aligning with Kawarabi\'s mission.

Ileocecal intussusception (ICI) is the most common abdominal emergency and cause of intestinal obstruction in young children, carrying a high risk of mortality and morbidity. Enteric viral infectious and inflammatory syndromes are known triggers for intussusception (ileoileal and ileocolic) by causing mesenteric lymphoid hyperplasia that may act as a leading point allowing the bowel to invaginate into itself. Gastrointestinal (GI) symptoms are common in children with coronavirus disease 2019 (COVID-19) infection, with a subset of patients solely having GI complaints at the time of presentation.  COVID-19 as a trigger for intussusception in children has been hypothesized and suggested in multiple cases reported to date, both during the acute phase of illness and as a part of multisystem inflammatory syndrome in children (MIS-C). We present a seven-month-old male who developed ICI and became a diagnostic dilemma due to viral co-infections and the gradual emergence of MIS-C during the hospital stay. We are describing this presentation in an attempt to expand the understanding of the implications of COVID-19 and MIS-C in this young and unique age group.

Multisystem inflammatory syndrome of childhood (MIS-C) is a recently described entity in pediatrics post-COVID-19 pandemic. Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome caused by an unregulated proliferation of macrophages as well as T lymphocytes. Both entities can be considered overlapping, although distinct criteria for each can be found in the literature. Herein, we report a patient with MIS-C post-COVID-19 infection, complicated with HLH secondary to Plasmodium falciparum malaria from a blood transfusion.

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 included in 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.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a secondary immune manifestation of COVID-19 involving multiple organ systems in the body, resulting in fever, skin rash, abdominal pain, nausea, shock, and cardiac dysfunction that often lead to hospitalization. Although many of these symptoms resolve following anti-inflammatory treatment, the long-term neurological and psychiatric sequelae of MIS-C are unknown. In this review, we will summarize two domains of the MIS-C disease course, 1) Neuroinflammation in the MIS-C brain and 2) Psychosocial disruptions resulting from stress and hospitalization. In both domains, we present existing clinical findings and hypothesize potential connections to psychiatric outcomes. This is the first review to conceptualize a holistic framework of psychiatric risk in MIS-C patients that includes neuroinflammatory and psychosocial risk factors. As cases of severe COVID-19 and MIS-C subside, it is important for clinicians to monitor outcomes in this vulnerable patient population.

Pediatric inflammatory, multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), also known as a multisystem inflammatory syndrome in children (MIS-C), is diagnosed in children who develop an inadequate inflammatory response after exposure to the SARS-CoV-2 virus. The pathogenesis of the abnormal response of the immune system to a previous SARS-COV-2 infection has not been explained. Similarly, the safety and effectiveness of COVID-19 vaccinations in this group of patients have become the subject of clinical discussion. Presenting experiences from many centers aims to answer this question. We present 4 cases of patients who suffered from PIMS-TS. Three of them were safely vaccinated against COVID-19 after illness. One patient developed PIMS-TS temporarily associated with COVID-19 vaccination. We also collected and discussed data from other centers.

We conducted an Umbrella review of eligible studies to evaluate what patient features have been investigated in the multisystem inflammatory syndrome in children (MIS-C) population, in order to guide future investigations. We comprehensively searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from December 1, 2019 to the May 6, 2022. The time period was limited to cover the coronavirus disease-2019 (COVID-19) pandemic period. The protocol was registered in the PROSPERO registry (CRD42022340228). Eligible studies included (1) a study population of pediatric patients ≤21 years of age diagnosed with MIS-C; (2) an original Systematic review or Mata-analysis; (3) published 2020 afterward; and (4) was published in English. A total of 41 studies met inclusion criteria and underwent qualitative analysis. 28 studies reported outcome data of MIS-C. 22 studies selected clinical features of MIS-C, and 6 studies chose demographic data as a main topic. The mortality rate for children with MIS-C was 1.9% (interquartile range (IQR) 0.48), the ICU admission rate was 72.6% (IQR 8.3), and the extracorporeal membrane oxygenation rate was 4.7% (IQR 2.0). A meta-analysis of eligible studies found that cerebral natriuretic peptide in children with MIS-C was higher than that in children with COVID-19, and that the use of intravenous immunoglobulin (IVIG) in combination with glucocorticoids to treat MIS-C compared to IVIG alone was associated with lower treatment failure. In the future, for patients with MIS-C, studies focused on safety of surgery requiring general anesthesia, risk factors, treatment, and long-term outcomes are warranted.

Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood.
A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included \"COVID-19 in children\", \"severe pediatric COVID-19\", and \"critical illness in children with COVID-19\".
Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines.
Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

Kawasaki disease (KD) is an acute medium-vessel vasculitis, mainly affecting infants older than six months and children under five years. It predisposes to the development of coronary artery aneurysms and constitutes the leading cause of acquired heart disease in children. Its diagnosis is based on clinical criteria, namely, fever lasting for ≥ five days together with at least four of the five principal clinical features of the disease. Occasionally, children with KD present with fever, but they fulfill only some of the five principal criteria, and this is described as incomplete KD. Furthermore, \"atypical\" KD is a term that is usually used for cases that appear with rather unusual clinical manifestations, which complicate clinical judgment and may delay diagnosis and treatment. In this case series, we present four cases of KD with rather unusual clinical features: a five-year-old boy with lobar pneumonia, a six-year-old girl with orange-brown chromonychia appearing on the 10th day of the disease, a 2.5-month-old infant with prolonged fever and urinary tract infection, and an 18-month-old infant with refractory KD and high suspicion of multisystem inflammatory syndrome in children (MIS-C). A literature review on the unusual manifestations of atypical KD was performed to identify clinical findings that must alert the clinician to consider this clinical entity.