Abstract: Background Despite that numerous researches have investigated the pathogenesis of Kawasaki disease (KD), including epidemiology, genetics, infection, immunity, and inflammation. However, the causes of KD is still not well underlined. Objective We analyzed the blood samples of KD patients and control cases using modified highthroughput metagenomics sequencing to identify the bacterial and viral composition and relative abundances, aiming to demonstrate the potential pathogenic virus of KD. Design Casecontrol study. Methods We collected the blood samples from KD patients and controls, then purification, extraction and sequencing of viruslike particles had been completed. After quality control of raw data, macrogenome was assembled by MEGAHIT software and species annotating was performed on kraken2. Obtaining relative abundance of each sample at different taxonomic levels (phylum, order, family, genus, and species), we normalized taxon abundance with the online tool Wekemo Bioincloud. The top 20 taxa were displayed and analyzed comparatively using linear discriminant analysis. LDA>2 was set as the criteria of significant differences in abundance between groups for filtering potential pathogenic species. Main outcome measures Relative abundance of each sample at different taxonomic levels (phylum, order, family, genus, and species). Results We found that there was little difference between KDs and the controls in terms of overall microorganism. Only phylum Cossaviricota and species Bacillussp Y1 were significantly different. However, there was a great significant difference between viral population annotations. The relative abundances of Uroviricota, Nucleocytoviricota, and Taleaviricota were significantly higher in controls compared with KD patients. Various genera, such as Orthohepadnavirus, Pegunavirus, Montyvirus, Orthonairovirus, Toursvirus, showed significantly higher relative abundance in KDs. In KD patients, the relative abundance of Woodchuckhepatitis virus, Propionibacterium virus (PHL112N00, ATCC29399BT, Pirate, and P105), Diadromus pulchellus toursvirus, and so on were significantly more abundant than that in controls. Conclusion Summarily, we screened out several candidates KD pathogenic viruses, like WHV, Orthonairovirus, and DpTV1. These viruses may be responsible for acute febrile illness or liver damage in KD patients, or they may be able to disrupt patients' immune systems, but further investigations are required.

Key words: Kawasaki disease, Virus infection, Metagenomics, High-throughput sequencing, Bioinformatics