Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a novel syndrome associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with varying clinical features. This study aimed to analyze the expression profiles of cytokines in blood, report the important clinical characteristics, and correlate these with the short- and mid-term outcomes. Methods: This cross-sectional study was conducted on hospitalized children with MIS-C from March 2021 to May 2022. Phenotypes were classified into two groups (A,B) according to the severity of the disease and the need for invasive respiratory support. Clinical features, laboratory parameters, and outcomes were reported. Results: We identified 60 children with MIS-C (mean age of 7.4 ± 3.8 years) compared to 30 age- and sex-matched controls with simple COVID-19. The clinical manifestations of MIS-C patients were fever (100%), respiratory (83.3%), GIT (80%), and conjunctivitis (80%). Twenty-seven MIS-C children (45%) required PICU admission due to shock and needed mechanical ventilation. Anemia, lymphopenia, and elevated levels of inflammatory and tissue injury markers were observed in the MIS-C groups (mainly B). High cytokine levels (IL-1β, IL-6, IFN-α, GM-CSF, and HMGB1) were observed acutely in the MIS-C children, and a persistent elevation of some cytokines were reported at midterm follow-up, especially in Group B. Conclusion: Robust inflammatory response to COVID-19 disease with elevated IL-1β, IL-6, and GM-CSF levels might explain the severity and outcome of the clinical syndrome.

Background and objectives: Dilated cardiomyopathy (DCM) is a rare cardiac disease characterised by left ventricular enlargement, reduced left ventricular contractility, and impaired systolic function. Childhood DCM is clinically and genetically heterogenous and associated with mutations in over 100 genes. The aim of this study was to identify novel variations associated with infantile DCM. Materials and Methods: Targeted next generation sequencing (NGS) of 181 cardiomyopathy-related genes was performed in three unrelated consanguineous families from Saudi Arabia. Variants were confirmed and their frequency established in 50 known DCM cases and 80 clinically annotated healthy controls. Results: The three index cases presented between 7 and 10 months of age with severe DCM. In Family A, there was digenic inheritance of two heterozygous variants: a novel variant in LAMA4 (c.3925G > A, p.Asp1309Asn) and a known DCM mutation in MYH7 (c.2770G > A; p.Glu924Lys). The LAMA4 p.Asp1309Asn variant was predicted to be likely pathogenic according to international guidelines. The other two families had no identifiable potentially deleterious variants. Conclusions: Inheritance of two genetic variants may have a synergistic or dose effect to cause severe DCM. We report of a novel p.Asp1309Asn variation associated with DCM. Targeted NGS is useful in the molecular diagnosis of DCM and to guide whole-family management and counselling.

Cardio-rheumatology is an evolving and interdisciplinary field lying at the intersection of rheumatology and cardiovascular medicine that recognizes that individuals with autoimmune and inflammatory rheumatic complications have a much higher likelihood of developing cardiovascular diseases (CVDs). Inflammasomes are multiprotein complexes stimulated by the immune system after the detection of pathogens or cellular injury. Inflammasomes undergo a two-stage activation process initiated by nuclear factor (NF)-κB, subsequently playing a crucial role in innate immunity through activation of caspase 1 and the consequent release of proinflammatory cytokines such as IL-18 and IL-1β. However, a loss of control of inflammasome activation can cause inflammatory diseases in humans. Recent studies have focused on the role of inflammasomes in inflammatory cascades implicated in the pathogenesis of several diseases. Here, we review inflammasome activation, its mechanism of action, and its role in CVD. In particular, we describe the role of inflammasomes in rheumatic heart disease, Kawasaki disease, familial Mediterranean fever, ankylosing spondylitis, and rheumatoid arthritis as exemplars to illustrate pathobiological mechanisms and the potential for targeting inflammasomes for therapeutic benefit.