A. Ramaswamy, N. Brodsky, T. Sumida, M. Comi, H. Asashima, K. Hoehn, N. Li, Y. Liu, A. Shah, N. Ravindra, J. Bishai, A. Khan, W. Lau, B. Sellers, N. Bansal, R. Sparks, A. Unterman, V. Habet, A. Rice, J. Catanzaro, H. Chandnani, M. López, N. Kaminski, C. D. Dela Cruz, J. Tsang, Z. Wang, X. Yan, S. Kleinstein, D. van Dijk, R. Pierce, D. Hafler, C. Lucas
medRxiv, 2020
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.
Cited by 10 publications.
Field of study: Medicine