A monocyte/dendritic cell molecular signature of SARS-CoV-2 related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis. de Cevins et al.

Published: 23 July 2021| Version 1 | DOI: 10.17632/wm4z48cftc.1
Marine Luka,
Nikaia Smith,
Sonia Meynier,
Aude Magérus,
Francesco Carbone,
Victor Garcia,
Laura Barnabei,
Maxime Batignes,
Alexandre Boulle,
Marie-Claude Stolzenberg,
Brieuc Pérot,
Bruno Charbit,
Tinhinane Fali,
Vithura Pirabarakan,
Boris Sorin,
Quentin Riller,
Ghaith Abdessalem,
Maxime Beretta,
Ludivine Grzelak,
Pedro Goncalves,
James Di Santo,
Hugo Mouquet,
Olivier Schwartz,
Mohammed Zarhrate,
Melanie Parisot,
Christine Bole-Feysot,
Cécile Masson,
Nicolas Cagnard,
Aurélien Corneau,
Camille Bruneau,
Shen-Ying Zhang,
Jean-Laurent Casanova,
Brigitte Bader Meunier,
Julien Haroche,
Isabelle Melki,
Mathie Lorrot,
Medhi Oualha,
Florence Moulin,
Damien Bonnet,
Zahra Belhadjer,
Mariane Leruez,
Slimane Allali,
Christele Gras Leguen,
Loic de Pontual,
Alain Fischer,
Darragh Duffy,
Frederic Rieux-Laucat,
Julie Toubiana,


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-kB activity, TNF-a signaling, associated with decreased gene expression of NF-kB inhibitors. 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.