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

Camille de Cevins 1, 2 Marine Luka 1 Nikaïa Smith 3 Sonia Meynier 4 Aude Magérus 4 Francesco Carbone 1 Víctor García-Paredes 1 Laura Barnabei 4 Maxime Batignes 1 Alexandre Boullé 1 Marie-Claude Stolzenberg 4 Brieuc Pérot 1 Bruno Charbit 5 Tinhinane Fali 1 Vithura Pirabarakan 4 Boris Sorin 4 Quentin Riller 4 Ghaith Abdessalem 1 Maxime Beretta 6 Ludivine Grzelak 7 Pedro Goncalves 8 James Di Santo 8 Hugo Mouquet 6 Olivier Schwartz 7 Mohammed Zarhrate 9, 10 Mélanie Parisot 9, 10 Christine Bole-Feysot 9, 10 Cécile Masson 10 Nicolas Cagnard 10 Aurélien Corneau 11 Camille Bruneau 4 Shen-Ying Zhang 12, 13 Jean-Laurent Casanova 12, 13, 14 Brigitte Bader Meunier 14 Julien Haroche 15 Isabelle Melki 14, 16 Mathie Lorrot 17 Mehdi Oualha 18 Florence Moulin 18 Damien Bonnet 19 Zahra Belhadjer 19 Marianne Leruez 20 Slimane Allali 21 Christèle Gras Leguen 22 Loïc de Pontual 23 Alain Fischer 14, 9, 24 Darragh Duffy 3, 5 Fredéric Rieux- Laucat 4 Julie Toubiana 21, 25 Mickaël Ménager 1
1 Equipe Inserm U1163 - Inflammatory Responses and Transcriptomic Networks in diseases
Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
4 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
11 PASS-CYPS - Cytométrie Pitié-Salpêtrière
PASS - Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé
12 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
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-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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Preprints, Working Papers, ...
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03244400
Contributor : Marie-Christine Vougny <>
Submitted on : Tuesday, June 1, 2021 - 11:11:05 AM
Last modification on : Wednesday, July 21, 2021 - 4:10:02 PM
Long-term archiving on: : Thursday, September 2, 2021 - 6:31:05 PM

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Camille de Cevins, Marine Luka, Nikaïa Smith, Sonia Meynier, Aude Magérus, et al.. A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis. 2021. ⟨pasteur-03244400⟩

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