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Response to: ‘Correspondence on ‘Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort’ by Pouletty et al’ by Pino et al
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  1. Naim Ouldali1,2,3,
  2. Marie Pouletty1,2,
  3. Johanna Lokmer4,
  4. Cherine Benzouid4,
  5. Constance Beyler4,
  6. Anna Deho5,
  7. Ulrich Meinzer1,2,6,7,
  8. Albert Faye1,2,3,
  9. Isabelle Melki1,2,8,9
  10. Great Paris Region (GPR) Kawa-COVID-19 consortium
    1. 1General Paediatrics, Department of Infectious Disease and Internal Medicine, Robert Debré University Hospital, AP-HP, Paris, France, Reference centre for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Paris, France
    2. 2Université de Paris, UFR de Médecine Paris Nord, Paris, France
    3. 3INSERM UMR 1123, ECEVE, Paris, France
    4. 4Cardiopaediatric Unit, Robert Debré University Hospital, AP-HP, Paris, France
    5. 5Paediatric Intensive Care Unit, Robert Debré University Hospital, AP-HP, Paris, France
    6. 6Center for Research on Inflammation, INSERM, UMR1149, Paris, France
    7. 7Biology and Genetics of Bacterial Cell Wall Unit, Pasteur Institute, Paris, France
    8. 8Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris, France
    9. 9Paediatric Hematology-Immunology and Rheumatology Department, Necker-Enfants-Malades University Hospital, AP-HP, Reference centre for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Paris, France
    1. Correspondence to Dr Isabelle Melki, Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris F-75019, France; isabelle.melki{at}aphp.fr

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    In their correspondence, Pino et al1 reported a cohort of 12 children with Kawasaki disease (KD) during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Barcelona, Spain. Among them, six had a positive SARS-CoV-2 infection confirmed by RT-PCR or serology while six had not. Interestingly, in line with our findings2 and reports from other settings,3–7 patients with multisystem inflammatory syndrome temporally associated with SARS-CoV-2 infection mimicking KD (Kawa-COVID-19) exhibited several differences as compared with classical KD, such as older age, higher inflammatory parameters, more frequent cytopenia and cardiac involvement, including myocarditis, often requiring haemodynamic support.1 2 These important discrepancies led to consider Kawasaki syndrome associated with SARS-CoV-2 infection as a distinct entity (Kawa-COVID-19,2 or multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19,8 or or paediatric inflammatory multisystem syndrom temporally associated with SARS-CoV-2 (PIMS-TS9). However, the possibility of a common pathway shared with classic KD has led to administer similar therapeutics to KD, including intravenous immunoglobulins (IVIG) and corticosteroids.3–7 If a substantial proportion of children were resistant to the first dose of IVIG, the large majority had a favourable short-term evolution with a second dose of IVIG±corticosteroids, as described by Pino et al and in our cohort.1 2

    The prognosis of KD is graved by its cardiac involvement,10 especially with coronary aneurysms, which are specific of KD and could occur several weeks after onset of disease. Therefore, a close surveillance is recommended during the months following KD diagnosis.10 Although only dilatations without aneurysms have been described at diagnosis by Pino et al and in our study, such complications have been described elsewhere in Kawa-COVID-19.3 11 This coronary involvement may be more frequent in patients with first-line IVIG resistance,10 12 raising concerns on the evolution of children with Kawa-COVID-19. To date, the middle-term evolution of these patients is unknown.

    In table 1, we described the clinical, biological and cardiac evolution of eight children, who developed a Kawa-COVID-19 in our tertiary hospital located in Paris, France. SARS-CoV-2 infection was confirmed in all of them either by nasopharyngeal SARS-CoV-2 RT-PCR or by SARS-CoV-2 serology (table 1). They had initial severe presentation with six myocarditis and required haemodynamic support in five cases. One month after the diagnosis, clinical and biological assessments were normal in all cases, without any persistent inflammatory syndrome, and all had normal cardiac ultrasounds (table 1).

    Table 1

    Evolution of children with Kawa-COVID-19 1 month after disease onset in one Great Paris Region tertiary centre, n=8

    These preliminary findings need to be confirmed with larger multicentre cohorts and a more prolonged follow-up, but suggest that despite an initial severe presentation with potentially life threatening cardiac involvement, the middle-term evolution of this specific entity may be reassuring. Finally, one of the main challenges of Kawa-COVID-19 may be the need for a long-term follow-up and cardiac assessment to better evaluate incidence and risk factors of coronary involvement and/or other cardiac dysfunctions and maybe deciphering physiological pathways responsible for this specific organ failure.

    References

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    Footnotes

    • Handling editor Josef S Smolen

    • Collaborators Great Paris Region (GPR) Kawa-COVID-19 consortium: Charlotte Borocco, M.D. (Department of Pediatric Rheumatology, Hôpital Bicêtre, AP-HP, Reference centre for Autoinflammatory diseases and amyloidosis (CEREMAIA), Le Kremlin-Bicêtre, France), Marion Caseris M.D. (General Paediatrics, Department of Infectious Disease and Internal Medicine, Robert Debré University Hospital, AP-HP, Paris, France, Reference centre for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Paris, France, Department of Microbiology, Robert Debré University Hospital, AP-HP, Paris, France), Romain Basmaci M.D., Ph.D. (Departments of General Paediatrics and Paediatric Emergency, Louis-Mourier Hospital, AP-HP, Colombes, France, Infection-Antimicrobials-Modelling-Evolution IAME, INSERM, UMR-1137, Université de Paris, 75018, Paris, France), Noémie Lachaume M.D. (Departments of General Paediatrics and Paediatric Emergency, Louis-Mourier Hospital, AP-HP, Colombes, France, Infection-Antimicrobials-Modelling-Evolution IAME, INSERM, UMR-1137, Université de Paris, 75018, Paris, France), Philippe Bensaid M.D. (Department of General Paediatrics, Victor Dupouy Hospital, Argenteuil, France), Samia Pichard M.D. (Department of General Paediatrics, Victor Dupouy Hospital, Argenteuil, France), Hanane Kouider M.D. (Department of General Paediatrics, René Dubos, Pontoise Hospital, France), Guillaume Morelle M.D. (Department of General Paediatrics Hôpital Bicêtre, AP-HP, Kremlin-Bicêtre, France), Irina Craiu M.D. (Paediatric emergency Department, Hôpital Bicêtre, AP-HP, Kremlin-Bicêtre, France), Corinne Pondarre M.D., Ph.D.(Sickle cell disease referal center, Centre hospitalier Intercommunal de Créteil, INSERM U955, Paris XII University), Arielle Maroni M.D. (Université de Paris, UFR de Médecine Paris Nord, 75010 Paris, France, Paediatric Intensive Care Unit, Robert Debré University Hospital, AP-HP, Paris, France), Mehdi Oualha M.D., Ph.D. (Paediatric Intensive Care Unit, Necker-Enfants-Malades University Hospital, AP-HP, Paris, France), Zahir Amoura M.D., M.Sc.(Sorbonne Université, Inserm UMR-S 1135, Department of Immunology and Infectious disease (CIMI-Paris), Pitié-Salpêtrière Hospital, AP-HP, Paris, France), Julien Haroche M.D., Ph.D. ((Sorbonne Université, Inserm UMR-S 1135, Department of Immunology and Infectious disease (CIMI-Paris), Pitié-Salpêtrière Hospital, AP-HP, Paris, France)), Juliette Chommeloux M.D. (Medical Intensive Care Unit, Institut de Cardiologie, AP-HP, Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France), Fanny Bajolle M.D., Ph.D.(Cardiopaediatric Unit, M3-C Necker-Enfants-Malades University Hospital, AP-HP, Paris, France), Stéphane Bonacorsi M.D., Ph.D. (Université de Paris, UFR de Médecine Paris Nord, 75010 Paris, France, Department of Microbiology, Robert Debré University Hospital, AP-HP, Paris, France, Infection-Antimicrobials-Modelling-Evolution IAME, INSERM, UMR-1137, Université de Paris, 75018, Paris, France), Guislaine Carcelain M.D., Ph.D. (Department of Immunology, Robert Debré University Hospital, AP-HP, Paris, France), Isabelle Kone-Paut M.D. (Department of Pediatric Rheumatology, Hôpital Bicêtre, AP-HP, Reference centre for Autoinflammatory diseases and amyloidosis (CEREMAIA), Le Kremlin-Bicêtre, France, Université de Paris Sud Saclay), Brigitte Bader-Meunier M.D. (Paediatric Hematology-Immunology and Rheumatology Department, Necker-Enfants-Malades University Hospital, AP-HP, Paris, France, Reference centre for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Paris, France, Laboratory of Immunogenetics of paediatric autoimmune diseases, INSERM UMR 1163, Paris, France), Caroline Galeotti M.D., Ph.D. (Department of Pediatric Rheumatology, Hôpital Bicêtre, AP-HP, Reference centre for Autoinflammatory diseases and amyloidosis (CEREMAIA), Le Kremlin-Bicêtre, France, Laboratory of Immunogenetics of paediatric autoimmune diseases, INSERM UMR 1163, Paris, France).

    • Contributors MP, NO, AF, UM and IM designed the study. MP, NO, JL, CBen, CBey, AD and IM collected clinical data. MP, NO, AF and IM analysed data. MP, CB, CG and IM wrote the paper. JL, CBen, CBey, AD, UM, AF 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 Not required.

    • 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 No 2014908).

    • Provenance and peer review Commissioned; internally peer reviewed.

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