Comparable bidirectional neutrophil immune dysregulation between Kawasaki disease and severe COVID-19

Abstract

Kawasaki disease (KD), a multisystem inflammatory syndrome that occurs in children, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) may share some overlapping mechanisms. The purpose of this study was to analyze the differences in single-cell RNA sequencing between KD and COVID-19. We performed single-cell RNA sequencing in KD patients (within 24 hours before IVIG treatment) and age-matched fever controls. The single-cell RNA sequencing data of COVID-19, influenza, and health controls were downloaded from the Sequence Read Archive (GSE149689/PRJNA629752). In total, 22 single-cell RNA sequencing data with 102,355 nuclei were enrolled in this study. After performing hierarchical and functional clustering analyses, two enriched gene clusters demonstrated similar patterns in severe COVID-19 and KD, heightened neutrophil activation, and decreased MHC class II expression. Furthermore, comparable dysregulation of neutrophilic granulopoiesis representing two pronounced hyperinflammatory states was demonstrated, which play a critical role in the overactivated and defective aging program of granulocytes, in patients with KD as well as those with severe COVID-19. In conclusion, both neutrophil activation and MHC class II reduction play a crucial role and thus may provide potential treatment targets for KD and severe COVID-19.

Identification of key signaling pathways and hub genes related to immune infiltration in Kawasaki disease with resistance to intravenous immunoglobulin based on weighted gene co-expression network analysis

“…It is reported that the number of neutrophils is considered as a clinical marker related to acute respiratory distress syndrome in COVID-19 patients ( Oishi et al, 2022 ). Moreover, one study has also demonstrated that similar neutrophilic dysregulation occurs in severe COVID-19 and KD two pronounced hyperinflammatory states, which plays a crucial role in the overactivation and defective aging program of granulocytes ( Chen K D et al, 2022 ). In short, based on the results of the KEGG enrichment analysis, we could conclude that these genes were more likely to be involved in neutrophil-related biological activities.…”

Hydrogen Gas Inhalation Treatment for Coronary Artery Lesions in a Kawasaki Disease Mouse Model

“…High-dose IVIG therapy and aspirin are commonly used treatments to reduce inflammation and prevent complications of CALs. However, even with treatment, some children may still develop CALs, highlighting the importance of close monitoring and other potential anti-inflammation agents [18,19].…”

B cell phenotype and serum levels of interferons, BAFF, and APRIL in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C)

“…Interestingly, in the case of SLE, it has been shown that neutrophils can contribute to an increase in BAFF and a strengthening of the autoimmune process. In the case of MIS-C, hallmarked by marked neutrophilia and disturbed neutrophil functionalities [ 25 , 26 ], a similar parallel might exist and contribute to the induction of autoimmunity [ 27 ].…”