COVID-19 and multisystem inflammatory syndrome in children and adolescents

Abstract

As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions. However, the association between multisystem inflammatory syndrome in children and COVID-19 is still unknown. We review the epidemiology, causes, clinical features, and current treatment protocols for multisystem inflammatory syndrome in children and adolescents associated with COVID-19. We also discuss the possible underlying pathophysiological mechanisms for COVID-19-induced inflammatory processes, which can lead to organ damage in paediatric patients who are severely ill. These insights provide evidence for the need to develop a clear case definition and treatment protocol for this new condition and also shed light on future therapeutic interventions and the potential for vaccine development. TRANSLATIONS: For the French, Chinese, Arabic, Spanish and Russian translations of the abstract see Supplementary Materials section.

Figure 1

Time course of MIS-C in PCR-positive COVID-19 cases Only incudes PCR-positive cases in London, UK. Data taken from Public Health England. Figure courtesy of Alasdair Bamford and Myrsini Kaforou. MIS-C=multisystem inflammatory syndrome in children. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.

Figure 2

Possible mechanisms of inflammatory processes for MIS-C Antibodies might enhance disease by increasing viral entry into cells. Alternative mechanisms include antibody or T-cell-mediated cell damage or activation of inflammation. Antibodies or T cells attack cells expressing viral antigens or attack host antigens which cross-react or mimic viral antigens. The low rate of virus detection in MIS-C would favour this second mechanism rather than the classic antibody-dependent enhancement. ACE2=angiotensin-converting enzyme 2. DAG=diacylglycerol. FcγR=Fc-gamma receptor. IL=interleukin. MCP=monocyte chemoattractant protein. MIS-C=multisystem inflammatory syndrome in children. MIP=macrophage inflammatory protein. PIK3=phosphoinositide 3 kinase. PKC=protein kinase C. PLCγ=phospholipase C gamma. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. SYK=tyrosine protein kinase SYK. TMPRSS2=transmembrane serine protease 2. TNF=tumour necrosis factor.

Figure 3

Pooled meta-analysis of patient characteristics in multisystem inflammatory syndrome in children associated with COVID-19, , , , , , , , , , , , , , , , , , , , , , , , , , , , Three case series were not included in the meta-analysis because of the overlap in cases. Cases reported in two studies, were also included in the case series reported by Feldstein and colleagues. Cases reported by Riphagen and colleagues were also included in the study by Whittaker and colleagues. The random-effect model is applied.