Multisystemic inflammatory syndrome following COVID-19 mRNA vaccine in children: a national post-authorization pharmacovigilance study

  1. Naïm Ouldali
  2. Haleh Bagheri
  3. Francesco Salvo
  4. Denise Antona
  5. Antoine Pariente
  6. Claire Leblanc
  7. Martine Tebacher
  8. Joëlle Micallef
  9. Corinne Levy
  10. Robert Cohen
  11. Etienne Javouhey
  12. Brigitte Bader-Meunier
  13. Caroline Ovaert
  14. Sylvain Renolleau
  15. Veronique Hentgen
  16. Isabelle Kone-Paut
  17. Nina Deschamps
  18. Loïc De Pontual
  19. Xavier Iriart
  20. Christelle Gras-Le Guen
  21. François Angoulvant
  22. Alexandre Belot
  23. the “French Covid-19 Paediatric Inflammation Consortium”
  24. the “French Pharmacovigilance network”
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Abstract

Importance

Multisystem 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.

Objective

To assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children.

Design, Setting, and Participants

Post-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.

Exposure

COVID-19 mRNA vaccine.

Main Outcome and Measures

The 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.

Results

From 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 Relevance

Very 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 points

Question

Is COVID-19 mRNA vaccine in 12-17-year-old children associated with subsequent multisystemic hyper-inflammatory syndrome?

Findings

The 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.

Meaning

Very 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.

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