SARS-CoV-2-related MIS-C: A key to the viral and genetic causes of Kawasaki disease?

Abstract

Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.

Figure 1.

Geographic distribution of COVID-19 and MIS-C cases. (A) Choropleth map of cumulative COVID-19 cases, by country, from World Health Organization data, as of February 11, 2021. (B) Choropleth map of MIS-C cases, by country, as reported in published studies. Countries that have reported cases but have not disclosed the number of cases are denoted as “# not reported.” Only MIS-C cases reported in English-language journals are included. A list of the articles included can be found in Table S1. NA, not applicable.

Figure 2.

A comparison of MIS-C and KD. The common and different clinical and immunological features of MIS-C and KD are shown. The major characteristic similarities or differences between the two conditions are highlighted in red. Th17, T helper type 17 cell.