Clinical and Immunological Manifestations in Multisystem Inflammatory Syndrome in Children Along With Endothelial Cell Damage

Fujioka K

Published on: 2022-06-20


Previous reports suggested that coronavirus disease 2019 (COVID-19) may be a systemic endothelial disease or a multi-organ disease including endothliitis, hypercoagulability, and cytokine storm, thereby therapeutic strategy is complicated especially in severe stage. With respect to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, the author emphasizes that it is important to estimate endothelial function in patients with Omicron variant, because this strain exhibited more efficient transduction of ACE2-expressing target cells, leading to endothelial dysfunction. Meanwhile, SARS-CoV-2 infection presents with mild and asymptomatic features in children. A rare post-infectious hyperinflammatory disease associated with SARS-CoV-2, so called multisystem inflammatory syndrome in children (MIS-C) has emerged. A novel hyperinflammatory disorder associated with COVID-19 showing severe Kawasaki disease-like features in children and adolescent in the UK, Italy, and USA has been reported. Center for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have developed case definition of MIS-C associated with COVID-19. In this article, the current knowledge of characteristic clinical and immunological presentations in MIS-C along with endothelial cell damage has been reviewed. Additionally, the therapeutic strategy and the efficacy of vaccination for MIS-C have been also summarized. The inflammatory response in MIS-C so called post-infectious hyperinflammatory diseases may differ from the cytokine storm of COVID-19. Based on the evidence, the author suggests that it may be important to estimate endothelial function assessed by flow-mediated vasodilation (FMD) test for risk stratification, follow-up of convalescence, and prediction of autoimmune disease in MIS-C patients. It is putative that cardiac dysfunction may be driven by the skewed cytokine responses toward IL-6 and IL-8 pathways than the magnitude of the cytokine storm in MIS-C patients. Based on the evidence, the continued use of recommended mRNA vaccine among all eligible individuals is supported, because MIS-C development after COVID-19 mRNA vaccination, compared to post-SARS-CoV-2 MIS-C disease, may be a rare disorder.