Exploring Factors Influencing Changes in Incidence and Severity of Multisystem Inflammatory Syndrome in Children

Abstract

Multisystem inflammatory syndrome (MIS-C) is a rare condition associated with COVID-19 affecting children, characterized by severe and aberrant systemic inflammation leading to nonspecific symptoms, such as gastrointestinal, cardiac, respiratory, hematological, and neurological disorders. In the last year, we have experienced a progressive reduction in the incidence and severity of MIS-C, reflecting the worldwide trend. Thus, starting from the overall trend in the disease in different continents, we reviewed the literature, hypothesizing the potential influencing factors contributing to the reduction in cases and the severity of MIS-C, particularly the vaccination campaign, the spread of different SARS-CoV-2 variants (VOCs), and the changes in human immunological response. The decrease in the severity of MIS-C and its incidence seem to be related to a combination of different factors rather than a single cause. Maturation of an immunological memory to SARS-CoV-2 over time, the implication of mutations of key amino acids of S protein in VOCs, and the overall immune response elicited by vaccination over the loss of neutralization of vaccines to VOCs seem to play an important role in this change.

“Multisystem Inflammatory Syndrome in Children”-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy

“…A SARS-CoV-2 infection primarily causes symptoms similar to the common flu, with patients presenting with fever, respiratory disorder and myalgia [1][2][3][4][5]. Soon, it was discovered that SARS-CoV-2 also affects the immune system by triggering hyper-inflammatory reactions, which eventually may cause a systemic illness called Multisystemic inflammatory syndrome in children, i.e., "MIS-C" [6][7][8][9][10]. However, vaccination against SARS-CoV-2 shows potential interactions with the immune system that may, in rare cases, cause similar disorders of autoimmune reactions and disorders [11,12].…”

Anti-Inflammatory and Immunomodulatory Effect of High-Dose Immunoglobulins in Children: From Approved Indications to Off-Label Use

“…Considering the infectious context in a more general way, on the one hand, it is important to recall the potential paradoxical detrimental effect of IVIG in infections sustained via Zika, Ebola, and SARS-CoV-2; this is driven by the so-called antibody-dependent enhancement mechanism in which low-titer, non-neutralizing antibodies bind to the viral particles, prompting their entry into the reticuloendothelial system via the Fc receptor and triggering an hyper-inflammatory response [304][305][306]. On the other hand, it is worth mentioning the promising role of IVIG in the management of organ transplantation-related pediatric infections.…”