• Chin-An Yang, Ya-Ling Huang, and Bor-Luen Chiang.
• College of Medicine, China Medical University, Taichung, 40402, Taiwan; Divisions of Laboratory Medicine and Pediatrics, China Medical University Hsinchu Hospital, Zhubei City, Hsinchu County, 302, Taiwan.
• J Formos Med Assoc. 2022 Mar 1; 121 (3): 623632623-632.

Background/PurposeThe association between dysregulated innate immune responses seen in Kawasaki disease (KD) with predisposition to Kawasaki-like multisystem inflammatory syndrome in children (MIS-C) remains unclear. We aimed to compare the innate immunity transcriptome signature between COVID-19 and KD, and to analyze the interactions of these molecules with genes known to predispose to KD.MethodsTranscriptome datasets of COVID-19 and KD cohorts (E-MTAB-9357, GSE-63881, GSE-68004) were downloaded from ArrayExpress for innate immune response analyses. Network analysis was used to determine enriched pathways of interactions.ResultsUpregulations of IRAK4, IFI16, STING, STAT3, PYCARD, CASP1, IFNAR1 and CD14 genes were observed in blood cells of acute SARS-CoV-2 infections with moderate severity. In the same patient group, increased expressions of TLR2, TLR7, IRF3, and CD36 were also noted in blood drawn a few days after COVID-19 diagnosis. Elevated blood PYCARD level was associated with severe COVID-19 in adults. Similar gene expression signature except differences in TLR8, NLRP3, STING and IRF3 levels was detected in KD samples. Network analysis on innate immune genes and genes associated with KD susceptibility identified enriched pathways of interactions. Furthermore, higher expression levels of KD susceptibility genes HLA-DOB, PELI1 and FCGR2A correlated with COVID-19 of different severities.ConclusionOur findings suggest that most enriched innate immune response pathways were shared between transcriptomes of KD and COVID-19 with moderate severity. Genetic polymorphisms associated with innate immune dysregulation and KD susceptibility, together with variants in STING and STAT3, might predict COVID-19 severity and potentially susceptibility to COVID-19 related MIS-C.Copyright © 2021. Published by Elsevier B.V.

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