@article{3102187,
    title = "Treatment of Multisystem Inflammatory Syndrome in Children",
    author = "McArdle, A.J. and Vito, O. and Patel, H. and Seaby, E.G. and Shah, P. and Wilson, C. and Broderick, C. and Nijman, R. and Tremoulet, A.H. and Munblit, D. and Ulloa-Gutierrez, R. and Carter, M.J. and De, T. and Hoggart, C. and Whittaker, E. and Herberg, J.A. and Kaforou, M. and Cunnington, A.J. and Levin, M. and Vazquez, J.A. and Carmona, R. and Perez, L. and Rubinos, M. and Veliz, N. and Yori, S. and Haerynck, F. and Hoste, L. and Leal, I.A. and Da Silva, A.R.A. and Silva, A.E.A. and Barchik, A. and Barreiro, S.T.A. and Cochrane, N. and Teixeira, C.H. and Arauj, J.M. and Ossa, R.A.P.-D.L. and Vieira, C.S. and Dimitrova, A. and Ganeva, M. and Stefanov, S. and Telcharova-Mihaylovska, A. and Biggs, C.M. and Scuccimarri, R. and Withington, D. and Raul, B.B. and Ampuero, C. and Aravena, J. and Casanova, D. and Cruces, P. and Diaz, F. and Garcia-Salum, T. and Godoy, L. and Medina, R.A. and Galaz, G.V. and Avila-Aguero, M.L. and Brenes-Chacon, H. and Ivankovich-Escoto, G. and Yock-Corrales, A. and Badib, A. and Badreldin, K. and Elkhashab, Y. and Heshmat, H. and Heinonen, S. and Angoulvant, F. and Belot, A. and Ouldali, N. and Beske, F. and Heep, A. and Masjosthusmann, K. and Reiter, K. and Heuvel, I.V.D. and Both, U.V. and Agrafiotou, A. and Antachopoulos, C. and Eleftheriou, I. and Farmaki, E. and Fotis, L. and Kafetzis, D. and Lampidi, S. and Liakopoulou, T. and Maritsi, D. and Michailidou, E. and Milioudi, M. and Mparmpounaki, I. and Papadimitriou, E. and Papaevangelou, V. and Roilides, E. and Tsiatsiou, O. and Tsolas, G. and Tsolia, M. and Vantsi, P. and Pineda, L.Y.B. and Aguilar, K.L.B. and Quintero, E.M.C. and Ip, P. and Kwan, M.Y.W. and Kwok, J. and Lau, Y.L. and To, K. and Wong, J.S.C. and David, M. and Farkas, D. and Kalcakosz, S. and Szekeres, K. and Zsigmond, B. and Aslam, N. and Andreozzi, L. and Bianco, F. and Bucciarelli, V. and Buonsenso, D. and Cimaz, R. and D'Argenio, P. and Dellepiane, R.M. and Fabi, M. and Mastrolia, M.V. and Mauro, A. and Mazza, A. and Romani, L. and Simonini, G. and Tipo, V. and Valentini, P. and Verdoni, L. and Reel, B. and Pace, D. and Torpiano, P. and Flores, M.F. and Domínguez, M.G. and Vargas, A.L.G. and Hernandez, L.L. and Figueroa, R.P.M. and Gaxiola, G.P. and Valadez, J. and Klevberg, S. and Knudsen, P.K. and Maseide, P.H. and Carrera, J.M. and Castano, E.G. and Timana, C.A.D. and Leon, T.D. and Estripeaut, D. and Levy, J. and Norero, X. and Record, J. and Rojas-Bonilla, M. and Iramain, R. and Hernandez, R. and Huaman, G. and Munaico, M. and Peralta, C. and Seminario, D. and Yarleque, E.H.Z. and Gadzinska, J. and Mandziuk, J. and Okarska-Napierała, M. and Alacheva, Z.A. and Alexeeva, E. and Ananin, P.V. and Antsupova, M. and Bakradze, M.D. and Bobkova, P. and Borzakova, S. and Chashchina, I.L. and Fisenko, A.P. and Gautier, M.S. and Glazyrina, A. and Kondrikova, E. and Korobyants, E. and Korsunskiy, A.A. and Kovygina, K. and Krasnaya, E. and Kurbanova, S. and Kurdup, M.K. and Mamutova, A.V. and Mazankova, L. and Mitushin, I.L. and Nargizyan, A. and Orlova, Y.O. and Osmanov, I.M. and Polyakova, A.S. and Romanova, O. and Samitova, E. and Sologub, A. and Spiridonova, E. and Tepaev, R.F. and Tkacheva, A.A. and Yusupova, V. and Zholobova, E. and Grasa, C.D. and Segura, N.L. and Martinon-Torres, F. and Melendo, S. and Echevarria, A.M. and Guzman, J.M.M. and Argueta, J.R.P. and Rivero-Calle, I. and Riviere, J. and Rodriguez-Gonzalez, M. and Rojo, P. and Manubens, J.S. and Soler-Palacin, P. and Soriano-Arandes, A. and Tagarro, A. and Villaverde, S. and Altman, M. and Brodin, P. and Horne, A. and Palmblad, K. and Brotschi, B. and Sauteur, P.M. and Schmid, J.P. and Prader, S. and Relly, C. and Schlapbach, L.J. and Seiler, M. and Truck, J. and Wutz, D. and Ketharanathan, N. and Vermont, C. and Ozkan, E.A. and Erdeniz, E.H. and Borisova, G. and Boychenko, L. and Diudenko, N. and Kasiyan, O. and Katerynych, K. and Melnyk, K. and Miagka, N. and Teslenko, M. and Trykosh, M. and Volokha, A. and Akomolafe, T. and Al-Abadi, E. and Alders, N. and Avram, P. and Bamford, A. and Bank, M. and Roy, R.B. and Beattie, T. and Boleti, O. and Broad, J. and Carrol, E.D. and Chandran, A. and Cooper, H. and Davies, P. and Emonts, M. and Evans, C. and Fidler, K. and Foster, C. and Gong, C. and Gongrun, B. and Gonzalez, C. and Grandjean, L. and Grant, K. and Hacohen, Y. and Hall, J. and Hassell, J. and Hesketh, C. and Hewlett, J. and Hnieno, A. and Holt-Davis, H. and Hossain, A. and Hudson, L.D. and Johnson, M. and Johnson, S. and Jyothish, D. and Kampmann, B. and Kavirayani, A. and Kelly, D. and Kucera, F. and Langer, D. and Lillie, J. and Longbottom, K. and Lyall, H. and MacKdermott, N. and Maltby, S. and McLelland, T. and McMahon, A.-M. and Miller, D. and Morrison, Z. and Mosha, K. and Muller, J. and Myttaraki, E. and Nadel, S. and Osaghae, D. and Osman, F. and Ostrzewska, A. and Panthula, M. and Papachatzi, E. and Papadopoulou, C. and Penner, J. and Polandi, S. and Prendergast, A.J. and Ramnarayan, P. and Rhys-Evans, S. and Riordan, A. and Rodrigues, C.M.C. and Romaine, S. and Seddon, J. and Shingadia, D. and Srivastava, A. and Struik, S. and Taylor, A. and Taylor, A. and Taylor, A. and Tran, S. and Tudor-Williams, G. and Van Der Velden, F. and Ventilacion, L. and Wellman, P.A. and Yanney, M.P. and Yeung, S. and Badheka, A. and Badran, S. and Bailey, D.M. and Burch, A.K. and Burns, J.C. and Cichon, C. and Cirks, B. and Dallman, M.D. and Delany, D.R. and Fairchok, M. and Friedman, S. and Geracht, J. and Langs-Barlow, A. and Mann, K. and Padhye, A. and Quade, A. and Ramirez, K.A. and Rockett, J. and Sayed, I.A. and Shahin, A.A. and Umaru, S. and Widener, R. and Angela, M.H. and Kandawasvika, G. and BATS Consortium",
    journal = "The New England journal of medicine",
    year = "2021",
    volume = "385",
    number = "1",
    pages = "11-22",
    publisher = "Massachussetts Medical Society",
    doi = "10.1056/NEJMoa2102968",
    keywords = "albumin;  biological marker;  blood marker;  C reactive protein;  ferritin;  glucocorticoid;  immunoglobulin;  troponin;  unclassified drug;  glucocorticoid;  immunoglobulin;  virus antibody, Article;  artificial ventilation;  child;  clinical feature;  cohort analysis;  coronary artery aneurysm;  coughing;  diarrhea;  disease severity;  echocardiography;  female;  fever;  headache;  heart left ventricle failure;  hospitalization;  human;  hyperglycemia;  hypertension;  immunotherapy;  inflammation;  irritability;  laboratory test;  lethargy;  lymphocyte;  major clinical study;  male;  mucocutaneous lymph node syndrome;  multiple organ failure;  observational study;  outcome assessment;  pediatric multisystem inflammatory syndrome;  preschool child;  primary outcome;  respiratory distress;  school child;  secondary outcome;  sore throat;  vomiting;  adolescent;  clinical trial;  combination drug therapy;  comparative study;  confidence interval;  immunology;  immunomodulation;  mortality;  multicenter study;  propensity score;  regression analysis;  systemic inflammatory response syndrome;  treatment outcome, Adolescent;  Antibodies, Viral;  Child;  Child, Preschool;  Cohort Studies;  Confidence Intervals;  COVID-19;  Drug Therapy, Combination;  Female;  Glucocorticoids;  Hospitalization;  Humans;  Immunoglobulins, Intravenous;  Immunomodulation;  Male;  Propensity Score;  Regression Analysis;  Respiration, Artificial;  SARS-CoV-2;  Systemic Inflammatory Response Syndrome;  Treatment Outcome",
    abstract = "BACKGROUND Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. Copyright © 2021 Massachusetts Medical Society."
}