Multisystemic inflammatory syndrome following COVID-19 mRNA vaccine in children: a national post-authorization pharmacovigilance study
Authors: Ouldali Naïm , Bagheri Haleh , Salvo Francesco , Antona Denise , Pariente Antoine , Leblanc Claire , Tebacher Martine , Micallef Joëlle , Levy Corinne , Cohen Robert , Javouhey Etienne , Bader-Meunier Brigitte , Ovaert Caroline , Renolleau Sylvain , Hentgen Veronique , Kone-Paut Isabelle , Deschamps Nina , De Pontual Loïc , Iriart Xavier , Guen Christelle Gras-Le , Angoulvant François , Belot Alexandre ,   the “French Covid-19 Paediatric Inflammation Consortium”,   the “French Pharmacovigilance network”
Published: January 2022

AbstractImportanceMultisystem inflammatory syndrome in children (MIS-C) is the most severe life-threatening clinical entity associated with pediatric SARS-CoV-2 infection. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown.ObjectiveTo assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children.Design, Setting, and ParticipantsPost-authorization national population-based surveillance using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines. All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12– 17-year-old children between June 15th, 2021 and January 1st, 2022, were reported. Each case was assessed for WHO MIS-C criteria. Causality assessment followed 2019 WHO recommendations.ExposureCOVID-19 mRNA vaccine.Main Outcome and MeasuresThe main outcome was the reporting rate of post-vaccine hyper-inflammatory syndrome per 1,000,000 COVID-19 mRNA vaccine doses in 12–17-year-old children. This reporting rate was compared to the MIS-C rate per 1,000,000 12–17-year-old children infected by SARS-CoV-2. Secondary outcomes included the comparison of clinical features between post-vaccine hyper-inflammatory syndrome and post SARS-CoV-2 MIS-C.ResultsFrom June 2021 to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12–17-year-old children. Among them, 9 presented a multisystemic hyper-inflammatory syndrome. All cases fulfilled MIS-C WHO criteria. Main clinical features included male predominance (8/9, 89%), cardiac involvement (8/9, 89%), digestive symptoms (7/9, 78%), coagulopathy (5/9, 54%), cytolytic hepatitis (4/9, 46%), and shock (3/9, 33%). 3/9 (33%) required intensive care unit transfer, and 2/9 (22%) hemodynamic support. All cases recovered. Only three cases had evidence of previous SARS-CoV-2 infection. The reporting rate was 1.1 (95%CI [0.5; 2.1]) per 1,000,000 doses injected. 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. Clinical features (inflammatory parameters, cytopenia) slightly differed from post-SARS-CoV-2 MIS-C, along with short-term outcomes (less PICU transfer than MIS-C).Conclusion and RelevanceVery few cases of hyper-inflammatory syndromes 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 MIS-C among same age children infected by SARS-CoV-2, supports the benefit of SARS-CoV-2 vaccination in children. Further studies are required to explore specific pathways of this entity compared to post-SARS-CoV-2 MIS-C.Key pointsQuestionIs COVID-19 mRNA vaccine in 12-17-year-old children associated with subsequent multisystemic hyper-inflammatory syndrome?FindingsThe French national pharmacovigilance system identified 9 children with a hyper-inflammatory syndrome with multi-organ involvement following COVID-19 mRNA vaccination (reporting rate 1.1 [0.5; 2.1] per 1,000,000 doses), of which only three had evidence of previous SARS-CoV-2 infection. All cases fulfilled WHO definition for MIS-C, but clinical and immunological features, along with short-term outcomes, slightly differed from classical post SARS-CoV-2 MIS-C.MeaningVery rare cases of hyper-inflammatory syndrome can occur following COVID-19 mRNA vaccine in 12-17-year-old children. The very low rate of this entity, compared to classical post-SARS-CoV-2 MIS-C, supports the benefit of SARS-CoV-2 vaccination in children.