The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C)

Abstract

Multisystem Inflammatory Syndrome in Children (MIS-C) is defined as a clinically serious condition requiring hospitalization with fever, multi-system organ disfunction, inflammatory biomarkers increase. The syndrome develops in the context of a probable or ascertained Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) infection, but other possible etiologies should be ruled out for definitive diagnosis. On the clinical side, along with the multi-system involvement, myocarditis with heart failure and shock is the most striking feature. Capillary leak is another fundamental feature of MIS-C. In fact, shock and hemodynamic compromise in MIS-C can occur also in the absence of laboratory evidence of myocardial inflammation, with preserved cardiac function and rapid reversibility. Since the first observations of MIS-C patients, it was evident that there is a delay between the peak of adult cases of Coronavirus disease 19 (COVID-19) and the MIS-C peak. Moreover, SARS-Cov2 isolation in children with MIS-C is not always possible, due to low viral load, while positive serology is far more commonly observed. These observations lead to the interpretation of MIS-C as a post-infectious disease. Although the exact pathogenesis of MIS-C is far from being elucidated, it is clear that it is a hyperinflammatory disease with a different inflammatory response as compared to what is seen in acute SARS-CoV-2 infection and that the disease shares some, but not all, immunological features with Macrophage Activation Syndrome (MAS), Kawasaki Disease (KD), Hemophagocytic Lymphohistiocytosis (HLH), and Toxic Shock Syndrome (TSS). Different mechanisms have been hypothesized as being responsible, from molecular mimicry to antibody dependent enhancement (ADE). Some evidence has also been collected on the immunological profile of patients with MIS-C and their difference from COVID-19. This review is focused on critical aspects of MIS-C clinical presentation and pathogenesis, and different immunological profiles. We propose a model where this hyperinflammatory disease represents one manifestation of the SARS-CoV2 spectrum in children, going from asymptomatic carriers to the post-infectious MIS-C, through symptomatic children, a low number of which may suffer from a severe infection with hyperinflammation (pediatric Hyper-COVID).

Multisystem Inflammatory Syndrome and Autoimmune Diseases Following COVID-19: Molecular Mechanisms and Therapeutic Opportunities

“…MIS-C is an uncommon but serious medical condition which is associated with SARS-CoV-2 ( Hasan et al, 2021 ). The disease seems to develop from a dysregulated immune response, resulting in endothelial dysfunction and a hyperinflammatory state, which eventually causes capillary leak, followed by multiorgan failure ( Panaro and Cattalini, 2021 ). MIS-C is characterized by inflammation in multiple organs such as the brain, kidneys, heart, eyes, lungs, skin, or gastrointestinal system ( Hasan et al, 2021 ).…”

“…MIS-C is characterized by inflammation in multiple organs such as the brain, kidneys, heart, eyes, lungs, skin, or gastrointestinal system ( Hasan et al, 2021 ). Therefore, the clinical picture can be wide, depending on the severity and organ manifestation ( Panaro and Cattalini, 2021 ). According to a recent systematic review, the most common symptoms were gastrointestinal symptoms (71%), with the incidence of vomiting (25%), diarrhea (27%), and abdominal pain (36%), followed by mucocutaneous manifestations (conjunctivitis, strawberry tongue, skin rash, and dried-cracked lips).…”

The Multifaceted Presentation of the Multisystem Inflammatory Syndrome in Children: Data from a Cluster Analysis

“…These criteria were introduced by employing limited data extracted from early reported cases. However, it is now well known that the disease does not have a single phenotype and that various symptoms and system involvements may accompany the disease [ 3 ]. Furthermore, patients presenting several months after a documented COVID-19 illness or after contact with a person having COVID-19 were reported [ 4 ].…”

Ofeleein i mi Vlaptin—Volume II: Immunity Following Infection or mRNA Vaccination, Drug Therapies and Non-Pharmacological Management at Post-Two Years SARS-CoV-2 Pandemic

“…Thus, antibody-dependent enhancement (ADE) may be a concern for people receiving vaccines based on the original Wuhan strain spike sequence, such as the current mRNA vaccines [13]. A variety of mechanisms has been postulated to be involved in ADE, which appears to be a limiting factor in the development of new vaccines and therapeutic approaches [14,15]. The rationale is to drive both high-specificity humoral and cellular immunity while avoiding undesirable consequences, such as ADE.…”