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
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. Method...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | EClinicalMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537023003899 |
| _version_ | 1827818039557488640 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Francesca Sperotto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:42:20Z |
| format | Article |
| id | doaj.art-8cb0959ec9ce4e99b1619c8db011de4a |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-03-12T00:42:20Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-8cb0959ec9ce4e99b1619c8db011de4a2023-09-15T04:40:11ZengElsevierEClinicalMedicine2589-53702023-10-0164102212Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortiumResearch in contextFrancesca Sperotto0Alba Gutiérrez-Sacristán1Simran Makwana2Xiudi Li3Valerie N. Rofeberg4Tianxi Cai5Florence T. Bourgeois6Gilbert S. Omenn7David A. Hanauer8Carlos Sáez9Clara-Lea Bonzel10Emily Bucholz11Audrey Dionne12Matthew D. Elias13Noelia García-Barrio14Tomás González González15Richard W. Issitt16Kate F. Kernan17Jessica Laird-Gion18Sarah E. Maidlow19Kenneth D. Mandl20Taha Mohseni Ahooyi21Cinta Moraleda22Michele Morris23Karyn L. Moshal24Miguel Pedrera-Jiménez25Mohsin A. Shah26Andrew M. South27Anastasia Spiridou28Deanne M. Taylor29Guillaume Verdy30Shyam Visweswaran31Xuan Wang32Zongqi Xia33Joany M. Zachariasse34Jane W. Newburger35Paul Avillach36James R. AaronAtif AdamGiuseppe AgapitoAdem AlbayrakGiuseppe AlbiMario AlessianiAnna AlloniDanilo F. AmendolaFrançois AngoulvantLi LLJ. AnthonyBruce J. AronowFatima AshrafAndrew AtzPaul AvillachVidul Ayakulangara PanickanPaula S. AzevedoRafael BadenesJames BalshiAshley BatugoBrendin R. Beaulieu-JonesBrett K. Beaulieu-JonesDouglas S. BellAntonio BellasiRiccardo BellazziVincent BenoitMichele BeraghiJosé Luis Bernal-SobrinoMélodie BernauxRomain BeySurbhi BhatnagarAlvar Blanco-MartínezMartin BoekerClara-Lea BonzelJohn BoothSilvano BosariFlorence T. BourgeoisRobert L. BradfordGabriel A. BratStéphane BréantNicholas W. BrownRaffaele BrunoWilliam A. BryantMauro BucaloEmily BucholzAnita BurgunTianxi CaiMario CannataroAldo CarmonaAnna Maria CattelanCharlotte CaucheteuxJulien ChampJin ChenKrista Y. ChenLuca ChiovatoLorenzo ChiudinelliKelly ChoJames J. CiminoTiago K. ColicchioSylvie CormontSébastien CossinJean B. CraigJuan Luis Cruz-BermúdezJaime Cruz-RojoArianna DagliatiMohamad DaniarChristel DanielPriyam DasBatsal DevkotaAudrey DionneRui DuanJulien DubielScott L. DuVallLoic EsteveHossein EstiriShirley FanRobert W. FollettThomas GanslandtNoelia García-BarrioLana X. GarmireNils GehlenborgEmily J. GetzenAlon GevaRachel SJ. GohTomás González GonzálezTobias GradingerAlexandre GramfortRomain GriffierNicolas GriffonOlivier GriselAlba Gutiérrez-SacristánPietro H. GuzziLarry HanDavid A. HanauerChristian HaverkampDerek Y. HazardBing HeDarren W. HendersonMartin HilkaYuk-Lam HoJohn H. HolmesJacqueline P. HonerlawChuan HongKenneth M. HulingMeghan R. HutchRichard W. IssittAnne Sophie JannotVianney JouhetMundeep K. KainthKernan F. KateRamakanth KavuluruMark S. KellerChris J. KennedyKate F. KernanDaniel A. KeyKatie KirchoffJeffrey G. KlannIsaac S. KohaneIan D. KrantzDetlef KraskaAshok K. KrishnamurthySehi L'YiJudith LeblancGuillaume LemaitreLeslie LenertDamien LeprovostMolei LiuNe Hooi Will LohQi LongSara Lozano-ZahoneroYuan LuoKristine E. LynchSadiqa MahmoodSarah E. MaidlowAdeline MakoudjouSimran MakwanaAlberto MaloviniKenneth D. MandlChengsheng MaoAnupama MaramMonika MaripuriPatricia MartelMarcelo R. MartinsJayson S. MarwahaAaron J. MasinoMaria MazzitelliDiego R. MazzottiArthur MenschMarianna MilanoMarcos F. MinicucciBertrand MoalTaha Mohseni AhooyiJason H. MooreCinta MoraledaJeffrey S. MorrisMichele MorrisKaryn L. MoshalSajad MousaviDanielle L. MoweryDouglas A. MuradShawn N. MurphyThomas P. NaughtonCarlos Tadeu Breda NetoAntoine NeurazJane NewburgerKee Yuan NgiamWanjiku FM. NjorogeJames B. NormanJihad ObeidMarina P. OkoshiKaren L. OlsonGilbert S. OmennNina OrlovaBrian D. OstasiewskiNathan P. PalmerNicolas ParisLav P. PatelMiguel Pedrera-JiménezAshley C. PfaffEmily R. PfaffDanielle PillionSara PizzimentiTanu PriyaHans U. ProkoschRobson A. PrudenteAndrea PrunottoVíctor Quirós-GonzálezRachel B. RamoniMaryna RaskinSiegbert RiegGustavo Roig-DomínguezPablo RojoNekane Romero-GarciaPaula Rubio-MayoPaolo SacchiCarlos SáezElisa SalamancaMalarkodi Jebathilagam SamayamuthuL. Nelson Sanchez-PintoArnaud SandrinNandhini SanthanamJanaina C.C. SantosFernando J. Sanz VidorretaMaria SavinoEmily R. SchriverPetra SchubertJuergen SchuettlerLuigia ScudellerNeil J. SebirePablo Serrano-BalazotePatricia SerreArnaud Serret-LarmandeMohsin A. ShahZahra Shakeri Hossein AbadDomenick SilvioPiotr SlizJiyeon SonCharles SondayAndrew M. SouthFrancesca SperottoAnastasia SpiridouZachary H. StrasserAmelia LM. TanBryce W.Q. TanByorn W.L. TanSuzana E. TanniDeanne M. TaylorAna I. Terriza-TorresValentina TibolloPatric TippmannEmma MS. TohCarlo TortiEnrico M. TrecarichiAndrew K. VallejosGael VaroquauxMargaret E. VellaGuillaume VerdyJill-Jênn VieShyam VisweswaranMichele VitaccaKavishwar B. WagholikarLemuel R. WaitmanXuan WangDemian WassermannGriffin M. WeberMartin WolkewitzScott WongZongqi XiaXin XiongYe YeNadir YehyaWilliam YuanJoany M. ZachariasseJanet J. ZahnerAlberto ZambelliHarrison G. ZhangDaniela ZöllerValentina ZuccaroChiara ZuccoDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, United States; Corresponding author. Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, United States.Department of Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, United StatesDepartment of Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, United StatesDepartment of Biostatistics, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, United StatesDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, United StatesDepartment of Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, United StatesDepartment of Pediatrics, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, United StatesDept of Computational Medicine & Bioinformatics, Internal Medicine, Human Genetics, & Public Health, University of Michigan, 2017 Palmer Commons, Ann Arbor, MI 48109-2218, United StatesDepartment of Learning Health Sciences, University of Michigan Medical School, 100-107 NCRC, 2800 Plymouth Road, Ann Arbor, MI 48109, United StatesBiomedical Data Science Lab, Instituto Universitario de Tecnologías de la Información y Comunicaciones, Universitat Politécnica de Valéncia, Camino de Vera S/N, Valencia 46022, SpainDepartment of Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, United StatesDepartment of Cardiology, Children's Hospital Colorado, University of Colorado Anschutz, 13123 E. 16th Ave, Aurora, CO 80045, United StatesDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, United StatesDivision of Cardiology, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA 19104, United StatesHealth Informatics, Hospital Universitario 12 de Octubre, Av. de Córdoba, s/n, Madrid 28041, SpainHealth Informatics, Hospital Universitario 12 de Octubre, Av. de Córdoba, s/n, Madrid 28041, SpainDigital Research, Informatics and Virtual Environments (DRIVE), Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, United KingdomDepartment of Critical Care Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15213, United StatesDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, United StatesMichigan Institute for Clinical and Health Research (MICHR) Informatics, University of Michigan, NCRC Bldg 400, 2800 Plymouth Road, Ann Arbor, MI 48109, United StatesComputational Health Informatics Program, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, United StatesDepartment of Biomedical Health Informatics, The Children's Hospital of Philadelphia, Roberts Building, 734 Schuylkill Ave, Philadelphia, PA 19146, United StatesPediatric Infectious Disease Department, Hospital Universitario 12 de Octubre, Av. de Córdoba, s/n, Madrid 28041, SpainDepartment of Biomedical Informatics, University of Pittsburgh, 5607 Baum Blvd, Pittsburgh, PA 15206, United StatesDepartment of Infectious Diseases, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, United KingdomHealth Informatics, Hospital Universitario 12 de Octubre, Av. de Córdoba, s/n, Madrid 28041, SpainDigital Research, Informatics and Virtual Environments (DRIVE), Great Ormond Street Hospital for Children, DRIVE, 40 Bernard St, London WC1N 1LE, United KingdomDepartment of Pediatrics-Section of Nephrology, Brenner Children’s, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, United StatesData Research, Innovation and Virtual Environments, Great Ormond Street Hospital for Children, DRIVE, 40 Bernard St, London WC1N 1LE, United KingdomDepartment of Biomedical Health Informatics, The Children's Hospital of Philadelphia, United States; The Department of Pediatrics, University of Pennsylvania Perelman Medical School, 3601 Civic Center Blvd, 6032 Colket, Philadelphia, PA 19104, United StatesIAM Unit, Bordeaux University Hospital, Place amélie rabat Léon, Bordeaux 33076, FranceDepartment of Biomedical Informatics, University of Pittsburgh, 5607 Baum Blvd, Pittsburgh, PA 15206, United StatesDepartment of Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, United StatesDepartment of Neurology, University of Pittsburgh, 3501 5th Avenue, BST-3 Suite 7014, Pittsburgh, PA 15260, United StatesDepartment of Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, United StatesDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, United StatesDepartment of Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, United States; Computational Health Informatics Program, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, United States; Corresponding author. Department of Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, United States.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.http://www.sciencedirect.com/science/article/pii/S2589537023003899Multisystem inflammatory syndromePaediatric inflammatory multisystem syndromeCOVID-19SARS-CoV-2VariantsPediatrics |
| spellingShingle | 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 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 EClinicalMedicine Multisystem inflammatory syndrome Paediatric inflammatory multisystem syndrome COVID-19 SARS-CoV-2 Variants Pediatrics |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Multisystem inflammatory syndrome Paediatric inflammatory multisystem syndrome COVID-19 SARS-CoV-2 Variants Pediatrics |
| url | http://www.sciencedirect.com/science/article/pii/S2589537023003899 |
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clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT martinwolkewitz clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT scottwong clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT zongqixia clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT xinxiong clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT yeye clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT nadiryehya clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT williamyuan clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT joanymzachariasse clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT janetjzahner clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT albertozambelli clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT harrisongzhang clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT danielazoller clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT valentinazuccaro clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext AT chiarazucco clinicalphenotypesandoutcomesinchildrenwithmultisysteminflammatorysyndromeacrosssarscov2varianterasamultinationalstudyfromthe4ceconsortiumresearchincontext |