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 P. 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 P. 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 M. Ménager (1)

1 Equipe Inserm U1163 - Inflammatory Responses and Transcriptomic Networks in diseases
2 Sanofi Aventis R&D [Chilly-Mazarin]
3 Immunologie Translationnelle - Translational Immunology lab
4 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
5 UTechS CB - Cytometrie et Biomarqueurs – Cytometry and Biomarkers
6 Immunologie humorale - Humoral Immunology
7 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
8 Immunité Innée - Innate Immunity
9 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
10 SFR Necker - UMS 3633 / US24 - Structure Fédérative de Recherche Necker
11 PASS-CYPS - Cytométrie Pitié-Salpêtrière
12 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
13 Rockefeller University [New York]
14 Service d'immuno-hématologie pédiatrique [CHU Necker]
15 Service d'Immunologie [CHU Pitié-Salpétrière]
16 AP-HP Hôpital universitaire Robert-Debré [Paris]
17 CHU Trousseau [APHP]
18 Département des urgences pédiatriques [CHU Necker]
19 CHU Necker - Enfants Malades [AP-HP]
20 Laboratoire de Virologie [CHU Necker]
21 Département de Pédiatrie et maladies infectieuses [CHU Necker]
22 CHU Nantes - Centre hospitalier universitaire de Nantes
23 Service de Pédiatrie [Jean Verdier]
24 CdF (institution) - Collège de France
25 Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens

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.

Domains: Life Sciences [q-bio]; Immunology

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⟩