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

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de Cevins, Camille | Luka, Marine | Smith, Nikaïa | Meynier, Sonia | Magérus, Aude | Carbone, Francesco | García-Paredes, Víctor | Barnabei, Laura | Batignes, Maxime | Boullé, Alexandre | Stolzenberg, Marie-Claude | Pérot, Brieuc, P. | Charbit, Bruno | Fali, Tinhinane | Pirabarakan, Vithura | Sorin, Boris | Riller, Quentin | Abdessalem, Ghaith | Beretta, Maxime | Grzelak, Ludivine | Goncalves, Pedro | Di Santo, James, P. | Mouquet, Hugo | Schwartz, Olivier | Zarhrate, Mohammed | Parisot, Mélanie | Bole-Feysot, Christine | Masson, Cécile | Cagnard, Nicolas | Corneau, Aurélien | Bruneau, Camille | Zhang, Shen-Ying | Casanova, Jean-Laurent | Meunier, Brigitte Bader | Haroche, Julien | Melki, Isabelle | Lorrot, Mathie | Oualha, Mehdi | Moulin, Florence | Bonnet, Damien | Belhadjer, Zahra | Leruez, Marianne | Allali, Slimane | Leguen, Christèle Gras | de Pontual, Loïc | Fischer, Alain | Duffy, Darragh | Laucat, Fredéric Rieux- | Toubiana, Julie | Ménager, Mickaël, M.

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Posté sur bioRxiv le 23/02/2021. 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-κB activity, TNF-α signaling, associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1α and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.

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