Camille de Cevins, Marine Luka, Nikaïa Smith, Sonia Meynier, Aude Magérus, Francesco Carbone, Víctor García-Paredes, Laura Barnabei, Maxime Batignes, Alexandre Boullé, Marie-Claude Stolzenberg, Brieuc P Pérot, Bruno Charbit, Tinhinane Fali, Vithura Pirabakaran, Boris Sorin, Quentin Riller, Ghaith Abdessalem, Maxime Beretta, Ludivine Grzelak, Pedro Goncalves, James P Di Santo, Hugo Mouquet, Olivier Schwartz, Mohammed Zarhrate, Mélanie Parisot, Christine Bole-Feysot, Cécile Masson, Nicolas Cagnard, Aurélien Corneau, Camille Brunaud, Shen-Ying Zhang, Jean-Laurent Casanova, Brigitte Bader-Meunier, Julien Haroche, Isabelle Melki, Mathie Lorrot, Mehdi Oualha, Florence Moulin, Damien Bonnet, Zahra Belhadjer, Marianne Leruez, Slimane Allali, Christèle Gras-Leguen, Loïc de Pontual, Alain Fischer, Darragh Duffy, Fredéric Rieux-Laucat, Julie Toubiana, Mickaël M Ménager
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引用次数: 36
Abstract
Background: Severe 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.
Methods: To 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.
Findings: The 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.
Conclusions: These results provide potential for a better understanding of disease pathophysiology.
Funding: Agence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d'Excellence ''Milieu Intérieur," grant ANR-10-LABX-69-01; ANR-flash Covid19 "AIROCovid" and "CoVarImm"), Institut National de la Santé et de la Recherche Médicale (INSERM), and the "URGENCE COVID-19" fundraising campaign of Institut Pasteur.
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