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

de Cevins, C.; Luka, M.; Smith, N.; Meynier, S.; Magerus, A.; Carbone, F.; Garcia Paredes, V.; Barnabei, L.; Batignes, M.; Boulle, A.; Stolzenberg, M.-C.; Perot, B. P.; Charbit, B.; Fali, T.; Pirabarakan, V.; Sorin, B.; Riller, Q.; Abdessalem, G.; Beretta, M.; Grzelak, L.; Goncalves, P.; Di Santo, J. P.; Mouquet, H.; Schwartz, O.; Zarhrate, M.; Parisot, M.; Bole-Feysot, C.; Masson, C.; Cagnard, N.; Corneau, A.; Bruneau, C.; Zhang, S.-Y.; Casanova, J.-L.; Bader Meunier, B.; Haroche, J.; Melki, I.; Lorrot, M.; Oualha, M.; Moulin, F.; Bonnet, D.; Belhadjer, Z.; Leruez, M.; Allali, S.; Gras Leguen

doi:10.1101/2021.02.23.432486

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bioRxiv · 10.1101/2021.02.23.432486

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

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Abstract

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 severe myocarditis, characterized by sustained NF-{kappa}B activity, TNF- signaling, associated with decreased gene expression of NF-{kappa}B inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1 and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.

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de Cevins, C., Luka, M., Smith, N., Meynier, S., Magerus, A., Carbone, F., Garcia Paredes, V., Barnabei, L., Batignes, M., Boulle, A., Stolzenberg, M.-C., Perot, B. P., Charbit, B., Fali, T., Pirabarakan, V., Sorin, B., Riller, Q., Abdessalem, G., Beretta, M., Grzelak, L., Goncalves, P., Di Santo, J. P., Mouquet, H., Schwartz, O., Zarhrate, M., Parisot, M., Bole-Feysot, C., Masson, C., Cagnard, N., Corneau, A., Bruneau, C., Zhang, S.-Y., Casanova, J.-L., Bader Meunier, B., Haroche, J., Melki, I., Lorrot, M., Oualha, M., Moulin, F., Bonnet, D., Belhadjer, Z., Leruez, M., Allali, S., Gras Leguen. 2021-02-23. A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis. https://doi.org/10.1101/2021.02.23.432486

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