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Innate immune response analysis in COVID-19 and kawasaki disease reveals MIS-C predictors
Chin-An Yang1, Ya-Ling Huang2, Bor-Luen Chiang3
1College 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.
Insights
Investigating Kawasaki disease (KD) and COVID-19, this study found shared innate immune pathways. Genetic factors influencing KD susceptibility may predict COVID-19 severity and MIS-C risk.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Kawasaki disease (KD) involves dysregulated innate immunity.
- The link between KD and COVID-19 related multisystem inflammatory syndrome in children (MIS-C) is unclear.
- Innate immune responses are crucial in both KD and COVID-19.
Purpose of the Study:
- Compare innate immune transcriptome signatures between COVID-19 and KD.
- Analyze interactions between these molecules and KD susceptibility genes.
- Investigate potential predictors of COVID-19 severity and MIS-C.
Main Methods:
- Transcriptome datasets from COVID-19 and KD cohorts were analyzed.
- Network analysis identified enriched interaction pathways.
- Gene expression signatures were compared between conditions.
Main Results:
- Shared upregulated innate immune genes (e.g., IRAK4, STING, STAT3) were found in moderate COVID-19 and KD.
- Elevated PYCARD levels correlated with severe COVID-19 in adults.
- KD susceptibility genes (e.g., HLA-DOB, PELI1) correlated with COVID-19 severity.
Conclusions:
- Innate immune pathways are largely shared between KD and moderate COVID-19.
- Genetic factors in KD susceptibility and innate immune dysregulation may predict COVID-19 severity.
- Variants in STING and STAT3 could indicate susceptibility to COVID-19 related MIS-C.
Background/Purpose:
The 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.
Methods:
Transcriptome 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.
Results:
Upregulations 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.
Conclusion:
Our 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.
