Abstract
A significant surge in cases of multisystem inflammatory syndrome in children (MIS-C, also called Pediatric Inflammatory Multisystem Syndrome - PIMS) has been observed amidst the COVID-19 pandemic. MIS-C shares many clinical features with Kawasaki disease (KD), although clinical course and outcomes are divergent. We analyzed whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues from these patients using a computational toolbox of two gene signatures, i.e., the 166-gene viral pandemic (ViP) signature, and its 20-gene severe (s)ViP subset that were developed in the context of SARS-CoV-2 infection and a 13-transcript signature previously demonstrated to be diagnostic for KD. Our analyses revealed that KD and MIS-C are on the same continuum of the host immune response as COVID-19. While both the pediatric syndromes converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures also revealed unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵† Consortia: Pediatric Emergency Medicine Kawasaki Disease Research Group (see Supplemental Online Material)
Main Article File: Title: Changed as requested by Reviewer #2 Abstract: Updated to reflect new studies and the revised abstract Results: Exhaustively edited to be responsive to the reviewer comments Discussion: Exhaustively edited to be responsive to the reviewer comments Figures: Fig 1: Revised to include new statistical analyses (1F) Fig 2: Revised to include new statistical analyses in panels 2B-C and 2F-G. Fig 3: New data and analyses included in panels 3A-D. Fig 4: New data and analyses included as panels 4D-G. Revised panel 4B. Fig 5: No changes Fig 6: Updated p values in panel 6A, formatted labeling and italics for gene names. oFig 7: Removed panel 7C Addition of Table 1. Addition of Methods to Main Article File Supplementary Online Materials: Edited for formatting purposes. Supplementary Information 1 Supplementary Information 2 Supplementary figures S1-3: