Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management

Abstract

Multisystem inflammatory syndrome (MIS-C) is a pediatric hyperinflammation disorder caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It has now been reported from several countries the world over. Some of the clinical manifestations of MIS-C mimic Kawasaki disease (KD) shock syndrome. MIS-C develops 4-6 weeks following SARS-CoV-2 infection, and is presumably initiated by adaptive immune response. Though it has multisystem involvement, it is the cardiovascular manifestations that are most prominent. High titres of anti-SARS-CoV-2 antibodies are seen in these patients. As this is a new disease entity, its immunopathogenesis is not fully elucidated. Whether it has some overlap with KD is still unclear. Current treatment guidelines recommend use of intravenous immunoglobulin and high-dose corticosteroids as first-line treatment. Mortality rates of MIS-C are lower compared to adult forms of severe COVID-19 disease.

Keywords: Coronavirus disease 2019; Hyperinflammation; Kawasaki disease (KD); Kawasaki-like disease; Multisystem inflammatory syndrome (MIS-C).

Fig. 1

Proposed immunological mechanism possibly triggered by antibody production in MIS-C. In genetically susceptible individuals, SARS-CoV-2 infections causes viral specific antibodies and there might be cross-reactive antibodies binding to host antigens. These antibodies may bind to Fcγ receptors in neutrophils and macrophages causing activation and secretion of pro-inflammatory cytokines that results in development of MIS-C. IFITM3 interferon-induced transmembrane protein-3, CD40LG cluster of differentiation 40 (CD40) ligand, HLA-B15:03 human leukocyte antigen (HLA) B15:03, ACE1 angiotensin-converting enzyme 1