Naïm Ouldali1,2,3, Julie Toubiana4,5, Denise Antona6, Etienne Javouhey7,8, Fouad Madhi9, Mathie Lorrot10, Pierre-Louis Léger11, Caroline Galeotti12, Caroline Claude13, Arnaud Wiedemann14,15, Noémie Lachaume16, Caroline Ovaert17,18, Morgane Dumortier19, Jean-Emmanuel Kahn20, Alexis Mandelcwajg21, Lucas Percheron22, Blandine Biot23, Jeanne Bordet24, Marie-Laure Girardin25, David Dawei Yang26, Marion Grimaud27, Mehdi Oualha27, Slimane Allali4, Fanny Bajolle28, Constance Beyler29, Ulrich Meinzer1,30, Michael Levy31, Ana-Maria Paulet32, Corinne Levy2,33, Robert Cohen2,33, Alexandre Belot34, François Angoulvant26,35. 1. Assistance Publique-Hôpitaux de Paris, Department of General Paediatrics, Paediatric Infectious Disease and Internal Medicine, Robert Debré University Hospital, Université de Paris, Paris, France. 2. ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France. 3. Université de Paris, INSERM UMR 1123, ECEVE, Paris, France. 4. Assistance Publique-Hôpitaux de Paris, Department of General Paediatrics and Paediatric Infectious Diseases, Necker-Enfants-Malades University Hospital, Université de Paris, Paris, France. 5. Institut Pasteur, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France. 6. Santé Publique France, Agence Nationale de Santé Publique, Saint-Maurice, France. 7. Hospices Civils de Lyon, Paediatric Intensive Care Unit, Hopital Femme, Mère Enfant, University of Lyon, Bron, France. 8. EA 7426 Pathophysiology of Injury-Induced Immunosuppression, University Claude Bernard Lyon 1, Hospices Civils of Lyon, Lyon, France. 9. Centre Hospitalier Intercommunal, Paediatric Department, Université Paris Est, IMRB-GRC GEMINI, Créteil, France. 10. Assistance Publique-Hôpitaux de Paris, Department of General Paediatric, Armand Trousseau University Hospital, Sorbonne Université, Paris, France. 11. Assistance Publique-Hôpitaux de Paris, Paediatric Intensive Care Unit, Armand Trousseau University Hospital, Sorbonne Université, Paris, France. 12. Assistance Publique-Hôpitaux de Paris, Department of Paediatric Rheumatology, Reference Centre for Autoinflammatory Diseases and Amyloidosis (CEREMAIA), Bicêtre University Hospital, Université de Paris Saclay, Le Kremlin-Bicêtre, France. 13. Assistance Publique-Hôpitaux de Paris, Paediatric Intensive Care Unit, Bicêtre University Hospital, Université de Paris Saclay, Le Kremlin-Bicêtre, France. 14. Children's Hospital, University Hospital of Nancy, Paediatric Department, Université de Lorraine, Vandoeuvre les Nancy, France. 15. INSERM UMRS 1256 NGERE, Nutrition, Genetics, and Environmental Risk Exposure, National Center of Inborn Errors of Metabolism, Université de Lorraine, Vandoeuvre les Nancy, France. 16. Assistance Publique-Hôpitaux de Paris, Paediatric Emergency Departement, Louis Mourier University Hospital, Colombes, France. 17. Assistance Publique-Hôpitaux de Marseille, Paediatric and Congenital Cardiology, Timone Hospital Marseille, University Hospital, Marseille, France. 18. INSERM, Marseille Medical Genetics, UMR 1251, Aix Marseille Université, Marseille, France. 19. Hôpital Femme Enfant Adolescent, Department of Paediatrics and Paediatric Emergency, University Hospital, Nantes, France. 20. Assistance Publique-Hôpitaux de Paris, Internal Medicine Department, Ambroise Paré University Hospital, Université Versailles-Saint Quentin-en-Yvelines, Boulogne-Billancourt, France. 21. Paediatric Department, Hôpital Delafontaine, Saint Denis, France. 22. Hôpital des Enfants, Paediatric Nephrology Department, Purpan University Hospital, Toulouse, France. 23. Paediatric Department, Hôpital de Valence, Valence, France. 24. Strasbourg University Hospital, Paediatric Cardiology Department, Hautepierre University Hospital, Strasbourg, France. 25. Paediatric Intensive Care Unit, Strasbourg University Hospital, Hautepierre University Hospital, Strasbourg, France. 26. Assistance Publique-Hôpitaux de Paris, Paediatric Emergency Department, Necker-Enfants Malades University Hospital, Université de Paris, Paris, France. 27. Assistance Publique-Hôpitaux de Paris, Paediatric Intensive Care Unit, Necker-Enfants Malades University Hospital, EA7323, Université de Paris, Paris, France. 28. Assistance Publique-Hôpitaux de Paris, M3C Department, Necker-Enfants Malades University Hospital, Université de Paris, Paris, France. 29. Assistance Publique-Hôpitaux de Paris, Cardiopaediatric Unit, Robert Debré University Hospital, Université de Paris, Paris, France. 30. Centre for Research on Inflammation, UMR1149, INSERM, Paris, France. 31. Assistance Publique-Hôpitaux de Paris, Paediatric Intensive Care Unit, Robert Debré University Hospital, Université de Paris, Paris, France. 32. Hôpital Nord Franche-Comté, Paediatric Department, Trévenans, France. 33. Centre Hospitalier Intercommunal, Research Centre, Université Paris Est, IMRB-GRC GEMINI, Créteil, France. 34. Hospices Civils de Lyon, Paediatric Nephrology, Rheumatology, Dermatology, Hopital Femme, Mère Enfant, Centre International de Recherche en Infectiologie/INSERM U1111, Bron, France. 35. INSERM, Centre de Recherche des Cordeliers, UMRS 1138, Sorbonne Université, Université de Paris, Paris, France.
Abstract
Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.
Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.
Authors: Lael M Yonker; Tal Gilboa; Alana F Ogata; Yasmeen Senussi; Roey Lazarovits; Brittany P Boribong; Yannic C Bartsch; Maggie Loiselle; Magali Noval Rivas; Rebecca A Porritt; Rosiane Lima; Jameson P Davis; Eva J Farkas; Madeleine D Burns; Nicola Young; Vinay S Mahajan; Soroush Hajizadeh; Xcanda I Herrera Lopez; Johannes Kreuzer; Robert Morris; Enid E Martinez; Isaac Han; Kettner Griswold; Nicholas C Barry; David B Thompson; George Church; Andrea G Edlow; Wilhelm Haas; Shiv Pillai; Moshe Arditi; Galit Alter; David R Walt; Alessio Fasano Journal: J Clin Invest Date: 2021-07-15 Impact factor: 14.808
Authors: Donald C Vinh; Laurent Abel; Paul Bastard; Matthew P Cheng; Antonio Condino-Neto; Peter K Gregersen; Filomeen Haerynck; Maria-Pia Cicalese; David Hagin; Pere Soler-Palacín; Anna M Planas; Aurora Pujol; Luigi D Notarangelo; Qian Zhang; Helen C Su; Jean-Laurent Casanova; Isabelle Meyts Journal: J Clin Immunol Date: 2021-06-08 Impact factor: 8.542