Clinical aspects and presumed etiology of multisystem inflammatory syndrome in children (MIS-C): A review

Abstract

The COVID-19 outbreak sparked by SARS-CoV-2, begat significant rates of malady worldwide, where children with an abnormal post-COVID ailment called the Multisystem Inflammatory Syndrome (MIS-C), were reported by April 2020. Here we have reviewed the clinical characteristics of the pediatric patients and the prognosis currently being utilized. A vivid comparison of MIS-C with other clinical conditions has been done. We have addressed the probable etiology and fundamental machinery of the inflammatory reactions, which drive organ failure. The involvement of androgen receptors portrays the likelihood of asymptomatic illness in children below adolescence, contributing to the concept of antibody-dependent enhancement.

Keywords: ACE2, Angiotensin-Converting Enzyme-2; ADE, Antibody-Dependent Enhancement; AR, Allosomal Androgen Receptor; ARDS, Acute Respiratory Distress Syndrome; BNP, Brain Natriuretic Peptide; CDC, Centres for Disease Control and Prevention; CRP, C-reactive protein; ESR, Erythrocyte Sedimentation Rate; IVIG, Intravenous Immunoglobulin; KD, Kawasaki Disease; Kawasaki disease; LVEF, Left Ventricular Ejection Fraction; MIS-C; MIS-C, Multisystem Inflammatory Syndrome in Children; Macrophage and antibody-dependent enhancement (ADE); Multiorgan failure; NLRP3, NLR family Pyrin Domain Containing 3; PCAID, Pediatric COVID-19 Associated Inflammatory Disorder; PIMS-TS, Pediatric Inflammatory Multisystem Syndrome Temporally Associated; PPT, Prolonged Prothrombin Time; PTT, The Prothrombin Time Test; Pediatric patient; RT-PCR, Real Time- Polymerase Chain Reaction; SARS-COV-2, Severe Acute Respiratory Syndrome Coronavirus 2; SARS-CoV-2; SHLH/MAS, Secondary Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome; TMPRSS2, Transmembrane Protease, Serine 2; TNP, Tumour Necrosis Factor; TSS, Toxic Shock Syndrome; TTSPs, Type II Transmembrane Serine Protease.

Fig. 1

Various types of MIS-C symptoms in pediatric patients. (Created withBioRender.com).

Fig. 2

The most likely mechanism for MIS-C expansion in pediatric patients.^,A. ACE-2 dependent pathway B. Antibody-dependent enhancement. (Created withBioRender.com). [ACE-2 = Angiotensin-converting enzyme 2. DAG = diacylglycerol. FcyR = Fc-gamma receptor. MIS-C = multisystem inflammatory syndrome in children. PIK3 = phosphoinositide 3 kinase. PKC = protein kinase C. PLC-y = phospholipase C gamma. SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. SYK = tyrosine protein kinase SYK. TMPRS52 = transmembrane serine protease 2.].