Hyper inflammatory syndrome following COVID-19 mRNA vaccine in children: A national post-authorization pharmacovigilance study
Naïm Ouldali, Haleh Bagheri, Francesco Salvo, Denise Antona, Alexandre Pariente, Claire LeBlanc, Martine Tebacher, Joëlle Micallef, Corinne Levy, Robert Cohen, Étienne Javouhey, Brigitte Bader‐Meunier, Caroline Ovaert, Sylvain Renolleau, Véronique Hentgen, Isabelle Koné‐Paut, Nina Deschamps, Loïc de Pontual, Xavier Iriart, Christelle Gras-Le Guen, François Angoulvant, Alexandre Bélot, A. Donzeau, Layal El Aridi, Sophie Léty, B. Leboucher, Agnes Baur, Lucas Jeusset, Maëlle Sélégny, Cristian Fedorczuk, Marion Lajus, Philippe Bensaïd, Yacine Laoudi, Charlotte Pons, Anne-Cécile Robert, Camille Beaucourt, Loïc de Pontual, Muriel Richard, Etienne Goisque, Xavier Iriart, Olivier Brissaud, Pierre Segretin, Julie Molimard, Marie-Clothilde Orecel, Gregoire Benoit, Lucille Bongiovanni, Margaux Guerder, Robin Pouyau, Jean-Marie De Guillebon De Resnes, Ellia Mezgueldi, Fleur Cour‐Andlauer, Côme Horvat, Pierre Poinsot, Cécile Frachette, Antoine Ouziel, Yves Gillet, Catherine Barrey, Jacques Brouard, F. Villedieu, Vathanaksambath Ro, Narcisse Elanga, Vincent Gajdos, Romain Basmaci, Hadile Mutar, Sébastien Rouget, Elodie Nattes, Isabelle Hau, Sandra Biscardi, Houmam El Jurdi, Camille Jung, Denis S. Semama, Frédéric Huet, Anne-Marie Zoccarato, Mayssa Sarakbi, Guillaume Mortamet, C. Bost-Bru, Joachim Bassil, Caroline Vinit, Véronique Hentgen, Pascal Leroux, Valérie Bertrand, Caroline Parrod, Irina Craiu, Isabelle Koné‐Paut, Philippe Durand, Pierre Tissiere, Caroline Claude, Guillaume Morelle, Tamazoust Guiddir, Charlotte Borocco, Fréderique Delion, Camille Guillot, Stéphane Leteurtre, François Dubos, Mylene Jouancastay, Alain Martinot, Valentine Voeusler, Jeanne Languepin, Nathalie Garrec, A. Chalvon Demersay
Abstract
Background: Multisystem inflammatory syndrome in children (MIS-C) is the most severe clinical entity associated with pediatric SARS-CoV-2 infection with a putative role of the spike protein into the immune system activation. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. We aimed to assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children. Methods: , 2022, were reported. Cases were reviewed according to WHO criteria for MIS-C. The reporting rate of this syndrome was compared to the MIS-C rate per 1,000,000 12-17-year-old children infected by SARS-CoV-2. Findings: Up to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12-17-year-old children. Among them, 12 presented a hyper-inflammatory syndrome with multisystemic involvement. Main clinical features included male predominance (10/12, 83%), cardiac involvement (10/12, 83%), digestive symptoms (10/12, 83%), coagulopathy (7/12, 58%), cytolytic hepatitis (6/12, 50%), and shock (5/12, 42%). 4/12 (33%) required intensive care unit transfer, and 3/12 (25%) hemodynamic support. All cases recovered. In eight cases, no evidence of previous SARS-CoV-2 infection was found. The reporting rate was 1.5 (95%CI [0.8; 2.6]) per 1,000,000 doses injected, i.e. 2.9 (95%CI [1.5; 5.1]) per 1,000,000 12-17-year-old vaccinated children. As a comparison, 113 MIS-C (95%CI [95; 135]) occurred per 1,000,000 12-17-year-old children infected by SARS-CoV-2. Interpretation: Very few cases of hyper-inflammatory syndrome with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12-17-year-old children. The low reporting rate of this syndrome, compared to the rate of post-SARS-CoV-2 MIS-C in the same age-group, largely supports the vaccination in a context of an important circulation of SARS-CoV-2. Funding: ESPID Fellowship Award; Grandir-Fonds de Solidarité Pour L'enfance.