Single-cell RNA sequencing reveals shared and distinct immune responses in Kawasaki disease and COVID-19

Introduction: The COVID-19 pandemic revealed clinical similarities with Kawasaki disease (KD), including vasculitis, but mechanisms of vascular injury remain unclear. This study used single-cell RNA sequencing (scRNA-seq) to explore immune mechanisms in vasculitis and validated findings in vitro. Methods: scRNA-seq was performed on PBMCs from six children with complete KD, three age-matched KD healthy controls (KHC), six COVID-19 patients (COV), three influenza patients (FLU), and four healthy controls (CHC). Findings were validated by flow cytometry and immunofluorescence in additional human samples. Monocyte adhesion assays, immunofluorescence, and qPCR assessed endothelial damage following monocyte interactions in HUVEC and THP-1 co-cultures. Results: Immune cell composition and transcriptional programs were altered in KD and COV. CD14+ monocytes were elevated in both KD and COV, sharing many differentially expressed genes (DEGs). CD14 and CD16 monocytes displayed differential activation linked to endothelial and epithelial dysfunction, respectively. SELL+/CCR1+/XAF1+ CD14 monocytes enhanced adhesion to and damage of endothelial cells. B-cell subsets differed between diseases, and T-cell activation was observed mainly in KD. Conclusion: Innate immune responses regulate endothelial dysfunction in both KD and COVID-19, whereas adaptive immunity activation differs. Monocytes in COVID-19 adhere to both endothelial and alveolar epithelial cells, suggesting mechanisms underlying shared KD/COVID-19 phenotypes.