An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease

Abstract

Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection, i.e., the viral pandemic (ViP) and severe-ViP signatures and a 13-transcript signature previously demonstrated to be diagnostic for KD, and validated our findings in whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues. Results show that KD and MIS-C are on the same continuum of the host immune response as COVID-19. Both the pediatric syndromes converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures reveal 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.

COVID-19 lung disease shares driver AT2 cytopathic features with Idiopathic pulmonary fibrosis

“…We not only formally define the nature of that host response and provide computational tools to measure the extent of such response, but also chart the cascade of cytopathic changes in the alveoli that are critical for the profibrogenic state. It is noteworthy that the same host immune response is seen also in MIS-C, a new disease that co-emerged with COVID-19, and in KD (which shares overlapping features with MIS-C in clinical presentation 35 ).…”

“…PIMS-TS). 35 To avoid overreliance on one set of signatures (i.e., ViP/sViP, which are tissue-agnostic signatures of host response), and increase the specificity for lung tissue, an independent gene signature was included, one that is induced in COVID-19 lung tissues, but not in influenza. 13 …”

“…PIMS-TS). 35 To avoid overreliance on one set of signatures (i.e., ViP/sViP, which are tissue-agnostic signatures of host response), and increase the specificity for lung tissue, an independent gene signature was included, one that is induced in COVID-19 lung tissues, but not in influenza. 13 We began first by using the ViP signatures as a starting computational framework to navigate the syndrome of COVID-19 lung disease, in conjunction with another independently reported 13 COVID-19-lung derived signature to identify idiopathic pulmonary fibrosis (IPF) 36 as a computational match for COVID-19 lung disease (Figure 1, Step 1).…”

Combination of Hemoglobin-for-Age Z-Score and Plasma Hepcidin Identified as a Novel Predictor for Kawasaki Disease

“…Meanwhile, the report by Delaye et al shows that higher hepcidin levels are critical in patients with COVID-19 compared to in non-COVID-19 patients with similar CRP levels [ 50 ]. Growing evidence has revealed that multisystem inflammatory syndrome associated (MIS-C) with COVID-19 in children shares many clinical features [ 51 ] and inflammatory responses with KD [ 52 ]. Until now, there is no result of hepcidin in MIS-C, and it is worth further research.…”

Complications of severe acute respiratory syndrome coronavirus 2 infection in children

“…Particular genetic determinants may also play a role as rare inborn errors of immunity altering the immune response to SARS-CoV-2 have been highlighted as possible pathogenetic factors of MIS-C in some children [24 ▪▪ ]. An artificial intelligence-guided signature revealed a host immune response shared between MIS-C and Kawasaki disease [25].…”