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

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.

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.