A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis
Camille de Cevins
(1, 2)
,
Marine Luka
(1, 3)
,
Nikaïa Smith
(4)
,
Sonia Meynier
(5)
,
Aude Magérus
(5)
,
Francesco Carbone
(1, 3)
,
Víctor García-Paredes
(1, 3)
,
Laura Barnabei
(5)
,
Maxime Batignes
(1)
,
Alexandre Boullé
(1)
,
Marie-Claude Stolzenberg
(5)
,
Brieuc P. Pérot
(1)
,
Bruno Charbit
(6)
,
Tinhinane Fali
(1)
,
Vithura Pirabakaran
(5)
,
Boris Sorin
(5)
,
Quentin Riller
(5)
,
Ghaith Abdessalem
(1)
,
Maxime Beretta
(7)
,
Ludivine Grzelak
(8)
,
Pedro Goncalves
(9)
,
James P. Di Santo
(9)
,
Hugo Mouquet
(7)
,
Olivier Schwartz
(8)
,
Mohammed Zarhrate
(10, 3)
,
Mélanie Parisot
(10, 3)
,
Christine Bole-Feysot
(10, 3)
,
Cécile Masson
(3)
,
Nicolas Cagnard
(3)
,
Aurélien Corneau
(11)
,
Camille Brunaud
(5)
,
Shen-Ying Zhang
(12, 13)
,
Jean-Laurent Casanova
(12, 13, 14)
,
Brigitte Bader-Meunier
(14)
,
Julien Haroche
(15, 16)
,
Isabelle Melki
(14, 17, 18)
,
Mathie Lorrot
(19)
,
Mehdi Oualha
(14, 18)
,
Florence Moulin
(14, 18)
,
Damien Bonnet
(14)
,
Zahra Belhadjer
(14)
,
Marianne Leruez
(14, 18)
,
Slimane Allali
(14, 18)
,
Christèle Gras-Leguen
(20)
,
Loïc de Pontual
(21, 22)
,
Pediatric-Biocovid Study Group
,
Alain Fischer
(14, 3, 23)
,
Darragh Duffy
(4, 6)
,
Fredéric Rieux-Laucat
(5)
,
Julie Toubiana
(14, 18, 24)
,
Mickaël Ménager
(1, 3)
1
Equipe Inserm U1163 -
Inflammatory Responses and Transcriptomic Networks in diseases
2 Sanofi Aventis R&D [Chilly-Mazarin]
3 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
4 Immunologie Translationnelle - Translational Immunology lab
5 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
6 UTechS CB - Cytometrie et Biomarqueurs – Cytometry and Biomarkers
7 Immunologie humorale - Humoral Immunology
8 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
9 Immunité Innée - Innate Immunity
10 UAR 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 Hôpital Necker - Enfants Malades [AP-HP]
15 CIMI - Centre d'Immunologie et des Maladies Infectieuses
16 CHU Pitié-Salpêtrière [AP-HP]
17 AP-HP Hôpital universitaire Robert-Debré [Paris]
18 UPCité - Université Paris Cité
19 CHU Trousseau [APHP]
20 CIC Nantes - Centre d’Investigation Clinique de Nantes
21 Hôpital Jean Verdier [AP-HP]
22 UP13 - Université Paris 13
23 CdF (institution) - Collège de France
24 Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens
2 Sanofi Aventis R&D [Chilly-Mazarin]
3 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
4 Immunologie Translationnelle - Translational Immunology lab
5 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
6 UTechS CB - Cytometrie et Biomarqueurs – Cytometry and Biomarkers
7 Immunologie humorale - Humoral Immunology
8 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
9 Immunité Innée - Innate Immunity
10 UAR 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 Hôpital Necker - Enfants Malades [AP-HP]
15 CIMI - Centre d'Immunologie et des Maladies Infectieuses
16 CHU Pitié-Salpêtrière [AP-HP]
17 AP-HP Hôpital universitaire Robert-Debré [Paris]
18 UPCité - Université Paris Cité
19 CHU Trousseau [APHP]
20 CIC Nantes - Centre d’Investigation Clinique de Nantes
21 Hôpital Jean Verdier [AP-HP]
22 UP13 - Université Paris 13
23 CdF (institution) - Collège de France
24 Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens
Nikaïa Smith
- Function : Author
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- ORCID : 0000-0002-0202-612X
- IdRef : 203218329
Francesco Carbone
- Function : Author
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Bruno Charbit
- Function : Author
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- ORCID : 0000-0002-5478-482X
Ludivine Grzelak
- Function : Author
- PersonId : 801252
- ORCID : 0000-0002-1298-7565
Pedro Goncalves
- Function : Author
- PersonId : 982811
- IdHAL : pedrogoncalves
James P. Di Santo
- Function : Author
- PersonId : 766326
- ORCID : 0000-0002-7146-1862
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Hugo Mouquet
- Function : Author
- PersonId : 945442
- ORCID : 0000-0002-4230-610X
- IdRef : 112571832
Olivier Schwartz
- Function : Author
- PersonId : 757442
- ORCID : 0000-0002-0729-1475
- IdRef : 128673850
Mélanie Parisot
- Function : Author
- PersonId : 778147
- ORCID : 0000-0003-4312-2035
Aurélien Corneau
- Function : Author
- PersonId : 183805
- IdHAL : aurelien-corneau
- ORCID : 0000-0003-1272-6872
Shen-Ying Zhang
- Function : Author
- PersonId : 760020
- ORCID : 0000-0002-9449-3672
- IdRef : 144474549
Jean-Laurent Casanova
- Function : Author
- PersonId : 756193
- ORCID : 0000-0002-7782-4169
- IdRef : 073388726
Brigitte Bader-Meunier
- Function : Author
- PersonId : 764839
- ORCID : 0000-0001-8476-8196
- IdRef : 058551522
Isabelle Melki
- Function : Author
- PersonId : 766552
- ORCID : 0000-0002-8057-333X
- IdRef : 158851897
Damien Bonnet
- Function : Author
- PersonId : 757220
- ORCID : 0000-0002-8722-5805
- IdRef : 067147569
Pediatric-Biocovid Study Group
- Function : Author
Darragh Duffy
- Function : Author
- PersonId : 746816
- IdHAL : darragh-duffy
- ORCID : 0000-0002-8875-2308
- IdRef : 201316919
Julie Toubiana
- Function : Author
- PersonId : 799686
- ORCID : 0000-0001-9561-669X
- IdRef : 150776640
Abstract
BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis.MethodsTo better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels.FindingsThe most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and 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 Vascular endothelial growth factor (VEGF) signaling.ConclusionsThese results provide potential for a better understanding of disease pathophysiology.
Origin | Files produced by the author(s) |
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