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Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort
  1. Marie Pouletty1,2,
  2. Charlotte Borocco3,4,
  3. Naim Ouldali1,5,
  4. Marion Caseris1,6,
  5. Romain Basmaci7,8,
  6. Noémie Lachaume7,8,
  7. Philippe Bensaid9,
  8. Samia Pichard9,
  9. Hanane Kouider10,
  10. Guillaume Morelle11,
  11. Irina Craiu12,
  12. Corinne Pondarre13,
  13. Anna Deho14,
  14. Arielle Maroni14,
  15. Mehdi Oualha15,
  16. Zahir Amoura16,17,
  17. Julien Haroche16,17,
  18. Juliette Chommeloux18,
  19. Fanny Bajolle19,
  20. Constance Beyler20,
  21. Stéphane Bonacorsi6,8,
  22. Guislaine Carcelain21,
  23. Isabelle Koné-Paut3,4,
  24. Brigitte Bader-Meunier22,23,
  25. Albert Faye1,2,5,
  26. Ulrich Meinzer1,2,24,25,
  27. Caroline Galeotti3,
  28. Isabelle Melki1,22,26
  1. 1 General Paediatrics, Department of Infectious Disease and Internal Medicine, Reference centre for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Paris, France, Robert Debré University Hospital, AP-HP, Paris, France
  2. 2 Université de Paris, UFR de Médecine Paris Nord, 75010 Paris, France
  3. 3 Department of Pediatric Rheumatology Reference centre for Autoinflammatory diseases and amyloidosis (CEREMAIA), Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France
  4. 4 Université Paris Sud-Saclay, UVSQ, 94276 Le Kremlin-Bicêtre, France
  5. 5 INSERM UMR 1123, ECEVE, Paris, France
  6. 6 Department of Microbiology, Robert Debré University Hospital,AP-HP, Paris, France
  7. 7 Departments of General Paediatrics and Paediatric Emergency, Louis-Mourier Hospital, AP-HP, Colombes, France
  8. 8 Infection-Antimicrobials-Modelling-Evolution IAME, INSERM, UMR-1137, Université de Paris, 75018, Paris, France
  9. 9 Department of General Paediatrics, Victor Dupouy Hospital, Argenteuil, France
  10. 10 Department of General Paediatrics, René Dubos, Pontoise Hospital, Pontoise, France
  11. 11 Department of General Paediatrics, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France
  12. 12 Paediatric emergency Department, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France
  13. 13 Sickle cell disease referal center, INSERM U955, Centre hospitalier Intercommunal de Créteil, Paris XII University, Créteil, France
  14. 14 Paediatric Intensive Care Unit, Robert Debré University Hospital, AP-HP, Paris, France
  15. 15 Paediatric Intensive Care Unit, Necker-Enfants-Malades University Hospital, AP-HP, Paris, France
  16. 16 Inserm UMR-S 1135, Sorbonne Université, Paris, France
  17. 17 Department of Immunology and Infectious disease (CIMI-Paris), Pitié-Salpêtrière Hospital, AP-HP, Paris, France
  18. 18 Medical Intensive Care Unit, Institut de Cardiologie, AP-HP, Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France
  19. 19 Cardiopaediatric Unit, M3-C, Necker-Enfants-Malades University Hospital, AP-HP, Paris, France
  20. 20 Cardiopaediatric Unit, Robert Debré University Hospital, AP-HP, Paris, France
  21. 21 Department of Immunology, Robert Debré University Hospital, AP-HP, Paris, France
  22. 22 Paediatric Hematology-Immunology and Rheumatology Department, Reference centre for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Paris, France, Necker-Enfants-Malades University Hospital, AP-HP, Paris, France
  23. 23 Laboratory of Immunogenetics of paediatric autoimmune diseases, INSERM UMR 1163, Paris, France
  24. 24 Center for Research on Inflammation, INSERM, UMR1149, Paris, France
  25. 25 Biology and Genetics of Bacterial Cell Wall Unit, Pasteur Institute, Paris, France
  26. 26 Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris, France
  1. Correspondence to Dr Isabelle Melki, General Paediatrics, Department of Infectious Disease and Internal Medicine, Reference centre for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Robert Debré University Hospital, AP-HP, Paris, France; isabelle.melki{at}aphp.fr

Abstract

Background Current data suggest that COVID-19 is less frequent in children, with a milder course. However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities.

Methods Multicentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (‘Kawa-COVID-19’). A historical cohort of ‘classical’ KD served as a comparator.

Results Sixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)). SARS-CoV-2 was detected in 12 cases (69%), while a further three cases had documented recent contact with a quantitative PCR-positive individual (19%). Cardiac involvement included myocarditis in 44% (n=7). Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L. Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment. The Kawa-COVID-19 cohort differed from a comparator group of ‘classical’ KD by older age at onset 10 vs 2 years (p<0.0001), lower platelet count (188 vs 383 G/L (p<0.0001)), a higher rate of myocarditis 7/16 vs 3/220 (p=0.0001) and resistance to first IVIg treatment 10/16 vs 45/220 (p=0.004).

Conclusion Kawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children. Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19.

Trial registration number

NCT02377245

  • inflammation
  • outcome and process assessment, health care
  • cytokines

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Footnotes

  • Handling editor Josef S Smolen

  • Correction notice This article has been corrected since it published Online First. Data within the 'Investigations consistent with prior SARS-CoV-2 infection' section and table 2 has been updated.

  • Contributors MP, NO, MC, UM and IM designed the study. MP, CB, GC, SB, CB, CG and IM collected clinical data. MP, NO and IM analysed data. MP, CB, CG and IM wrote the paper. CG, MC, UM, AF, IK-P, BB-M and IM supervised the study. All authors have read final approval of the version published.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Patient consent for publication Parental/guardian consent obtained.

  • Ethics approval The study protocol followed ethics guidelines (CPP no.CO-10–002) and was approved by the Advisory Committee on Information Processing in Research in the Field of Health (no.10.155bis) and the National Commission of Informatics and Freedom (CNIL N°2014908).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. De-identified participant data may be available upon reasonable request by sending an email to marie.pouletty@aphp.fr or isabelle.melki@aphp.fr.

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