A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis [Single cell RNAseq]

SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of myocarditis, characterized by sustained NF-kB activity, associated with decreased gene expression of NF-kB inhibitors and TNF-a signaling . We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1a and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology. Overall design: scRNAseq on PBMC from 9 CTL (two of which had replicates), 1 Acute-Inf (CoV2-), 4 Acute-Inf (CoV2+), 2 MIS-C (CoV2+), 6 MIS-C_MYO (CoV2+) and 2 KD (CoV2-)