EClinicalMedicine (Oct 2023)

Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortiumResearch in context

  • Francesca Sperotto,
  • Alba Gutiérrez-Sacristán,
  • Simran Makwana,
  • Xiudi Li,
  • Valerie N. Rofeberg,
  • Tianxi Cai,
  • Florence T. Bourgeois,
  • Gilbert S. Omenn,
  • David A. Hanauer,
  • Carlos Sáez,
  • Clara-Lea Bonzel,
  • Emily Bucholz,
  • Audrey Dionne,
  • Matthew D. Elias,
  • Noelia García-Barrio,
  • Tomás González González,
  • Richard W. Issitt,
  • Kate F. Kernan,
  • Jessica Laird-Gion,
  • Sarah E. Maidlow,
  • Kenneth D. Mandl,
  • Taha Mohseni Ahooyi,
  • Cinta Moraleda,
  • Michele Morris,
  • Karyn L. Moshal,
  • Miguel Pedrera-Jiménez,
  • Mohsin A. Shah,
  • Andrew M. South,
  • Anastasia Spiridou,
  • Deanne M. Taylor,
  • Guillaume Verdy,
  • Shyam Visweswaran,
  • Xuan Wang,
  • Zongqi Xia,
  • Joany M. Zachariasse,
  • Jane W. Newburger,
  • Paul Avillach,
  • James R. Aaron,
  • Atif Adam,
  • Giuseppe Agapito,
  • Adem Albayrak,
  • Giuseppe Albi,
  • Mario Alessiani,
  • Anna Alloni,
  • Danilo F. Amendola,
  • François Angoulvant,
  • Li LLJ. Anthony,
  • Bruce J. Aronow,
  • Fatima Ashraf,
  • Andrew Atz,
  • Paul Avillach,
  • Vidul Ayakulangara Panickan,
  • Paula S. Azevedo,
  • Rafael Badenes,
  • James Balshi,
  • Ashley Batugo,
  • Brendin R. Beaulieu-Jones,
  • Brett K. Beaulieu-Jones,
  • Douglas S. Bell,
  • Antonio Bellasi,
  • Riccardo Bellazzi,
  • Vincent Benoit,
  • Michele Beraghi,
  • José Luis Bernal-Sobrino,
  • Mélodie Bernaux,
  • Romain Bey,
  • Surbhi Bhatnagar,
  • Alvar Blanco-Martínez,
  • Martin Boeker,
  • Clara-Lea Bonzel,
  • John Booth,
  • Silvano Bosari,
  • Florence T. Bourgeois,
  • Robert L. Bradford,
  • Gabriel A. Brat,
  • Stéphane Bréant,
  • Nicholas W. Brown,
  • Raffaele Bruno,
  • William A. Bryant,
  • Mauro Bucalo,
  • Emily Bucholz,
  • Anita Burgun,
  • Tianxi Cai,
  • Mario Cannataro,
  • Aldo Carmona,
  • Anna Maria Cattelan,
  • Charlotte Caucheteux,
  • Julien Champ,
  • Jin Chen,
  • Krista Y. Chen,
  • Luca Chiovato,
  • Lorenzo Chiudinelli,
  • Kelly Cho,
  • James J. Cimino,
  • Tiago K. Colicchio,
  • Sylvie Cormont,
  • Sébastien Cossin,
  • Jean B. Craig,
  • Juan Luis Cruz-Bermúdez,
  • Jaime Cruz-Rojo,
  • Arianna Dagliati,
  • Mohamad Daniar,
  • Christel Daniel,
  • Priyam Das,
  • Batsal Devkota,
  • Audrey Dionne,
  • Rui Duan,
  • Julien Dubiel,
  • Scott L. DuVall,
  • Loic Esteve,
  • Hossein Estiri,
  • Shirley Fan,
  • Robert W. Follett,
  • Thomas Ganslandt,
  • Noelia García-Barrio,
  • Lana X. Garmire,
  • Nils Gehlenborg,
  • Emily J. Getzen,
  • Alon Geva,
  • Rachel SJ. Goh,
  • Tomás González González,
  • Tobias Gradinger,
  • Alexandre Gramfort,
  • Romain Griffier,
  • Nicolas Griffon,
  • Olivier Grisel,
  • Alba Gutiérrez-Sacristán,
  • Pietro H. Guzzi,
  • Larry Han,
  • David A. Hanauer,
  • Christian Haverkamp,
  • Derek Y. Hazard,
  • Bing He,
  • Darren W. Henderson,
  • Martin Hilka,
  • Yuk-Lam Ho,
  • John H. Holmes,
  • Jacqueline P. Honerlaw,
  • Chuan Hong,
  • Kenneth M. Huling,
  • Meghan R. Hutch,
  • Richard W. Issitt,
  • Anne Sophie Jannot,
  • Vianney Jouhet,
  • Mundeep K. Kainth,
  • Kernan F. Kate,
  • Ramakanth Kavuluru,
  • Mark S. Keller,
  • Chris J. Kennedy,
  • Kate F. Kernan,
  • Daniel A. Key,
  • Katie Kirchoff,
  • Jeffrey G. Klann,
  • Isaac S. Kohane,
  • Ian D. Krantz,
  • Detlef Kraska,
  • Ashok K. Krishnamurthy,
  • Sehi L'Yi,
  • Judith Leblanc,
  • Guillaume Lemaitre,
  • Leslie Lenert,
  • Damien Leprovost,
  • Molei Liu,
  • Ne Hooi Will Loh,
  • Qi Long,
  • Sara Lozano-Zahonero,
  • Yuan Luo,
  • Kristine E. Lynch,
  • Sadiqa Mahmood,
  • Sarah E. Maidlow,
  • Adeline Makoudjou,
  • Simran Makwana,
  • Alberto Malovini,
  • Kenneth D. Mandl,
  • Chengsheng Mao,
  • Anupama Maram,
  • Monika Maripuri,
  • Patricia Martel,
  • Marcelo R. Martins,
  • Jayson S. Marwaha,
  • Aaron J. Masino,
  • Maria Mazzitelli,
  • Diego R. Mazzotti,
  • Arthur Mensch,
  • Marianna Milano,
  • Marcos F. Minicucci,
  • Bertrand Moal,
  • Taha Mohseni Ahooyi,
  • Jason H. Moore,
  • Cinta Moraleda,
  • Jeffrey S. Morris,
  • Michele Morris,
  • Karyn L. Moshal,
  • Sajad Mousavi,
  • Danielle L. Mowery,
  • Douglas A. Murad,
  • Shawn N. Murphy,
  • Thomas P. Naughton,
  • Carlos Tadeu Breda Neto,
  • Antoine Neuraz,
  • Jane Newburger,
  • Kee Yuan Ngiam,
  • Wanjiku FM. Njoroge,
  • James B. Norman,
  • Jihad Obeid,
  • Marina P. Okoshi,
  • Karen L. Olson,
  • Gilbert S. Omenn,
  • Nina Orlova,
  • Brian D. Ostasiewski,
  • Nathan P. Palmer,
  • Nicolas Paris,
  • Lav P. Patel,
  • Miguel Pedrera-Jiménez,
  • Ashley C. Pfaff,
  • Emily R. Pfaff,
  • Danielle Pillion,
  • Sara Pizzimenti,
  • Tanu Priya,
  • Hans U. Prokosch,
  • Robson A. Prudente,
  • Andrea Prunotto,
  • Víctor Quirós-González,
  • Rachel B. Ramoni,
  • Maryna Raskin,
  • Siegbert Rieg,
  • Gustavo Roig-Domínguez,
  • Pablo Rojo,
  • Nekane Romero-Garcia,
  • Paula Rubio-Mayo,
  • Paolo Sacchi,
  • Carlos Sáez,
  • Elisa Salamanca,
  • Malarkodi Jebathilagam Samayamuthu,
  • L. Nelson Sanchez-Pinto,
  • Arnaud Sandrin,
  • Nandhini Santhanam,
  • Janaina C.C. Santos,
  • Fernando J. Sanz Vidorreta,
  • Maria Savino,
  • Emily R. Schriver,
  • Petra Schubert,
  • Juergen Schuettler,
  • Luigia Scudeller,
  • Neil J. Sebire,
  • Pablo Serrano-Balazote,
  • Patricia Serre,
  • Arnaud Serret-Larmande,
  • Mohsin A. Shah,
  • Zahra Shakeri Hossein Abad,
  • Domenick Silvio,
  • Piotr Sliz,
  • Jiyeon Son,
  • Charles Sonday,
  • Andrew M. South,
  • Francesca Sperotto,
  • Anastasia Spiridou,
  • Zachary H. Strasser,
  • Amelia LM. Tan,
  • Bryce W.Q. Tan,
  • Byorn W.L. Tan,
  • Suzana E. Tanni,
  • Deanne M. Taylor,
  • Ana I. Terriza-Torres,
  • Valentina Tibollo,
  • Patric Tippmann,
  • Emma MS. Toh,
  • Carlo Torti,
  • Enrico M. Trecarichi,
  • Andrew K. Vallejos,
  • Gael Varoquaux,
  • Margaret E. Vella,
  • Guillaume Verdy,
  • Jill-Jênn Vie,
  • Shyam Visweswaran,
  • Michele Vitacca,
  • Kavishwar B. Wagholikar,
  • Lemuel R. Waitman,
  • Xuan Wang,
  • Demian Wassermann,
  • Griffin M. Weber,
  • Martin Wolkewitz,
  • Scott Wong,
  • Zongqi Xia,
  • Xin Xiong,
  • Ye Ye,
  • Nadir Yehya,
  • William Yuan,
  • Joany M. Zachariasse,
  • Janet J. Zahner,
  • Alberto Zambelli,
  • Harrison G. Zhang,
  • Daniela Zöller,
  • Valentina Zuccaro,
  • Chiara Zucco

Journal volume & issue
Vol. 64
p. 102212

Abstract

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Summary: Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES −1.18 years [95% CI −2.05, −0.32]), had fewer respiratory symptoms (RD −0.15 [95% CI −0.33, −0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD −0.35 [95% CI −0.64, −0.07]), lower lymphocyte count (ES −0.16 × 109/uL [95% CI −0.30, −0.01]), lower C-reactive protein (ES −28.5 mg/L [95% CI −46.3, −10.7]), and lower troponin (ES −0.14 ng/mL [95% CI −0.26, −0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES −1.6 years [95% CI −2.5, −0.8]), had less frequent SIRS (RD −0.18 [95% CI −0.30, −0.05]), lower lymphocyte count (ES −0.39 × 109/uL [95% CI −0.52, −0.25]), lower troponin (ES −0.16 ng/mL [95% CI −0.30, −0.01]) and less frequently received anticoagulation therapy (RD −0.19 [95% CI −0.37, −0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (−1.3 days [95% CI −2.3, −0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None.

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