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Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3249 (Published 27 August 2020) Cite this as: BMJ 2020;370:m3249

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  1. Olivia V Swann, clinical lecturer in paediatric infectious diseases1 2,
  2. Karl A Holden, NIHR academic clinical fellow in paediatrics3 4,
  3. Lance Turtle, consultant in adult infectious diseases5 6,
  4. Louisa Pollock, consultant in paediatric infectious diseases7,
  5. Cameron J Fairfield, clinical research fellow8,
  6. Thomas M Drake, clinical research fellow8,
  7. Sohan Seth, senior data scientist9,
  8. Conor Egan, masters student9,
  9. Hayley E Hardwick, project manager5,
  10. Sophie Halpin, supervising data manager10,
  11. Michelle Girvan, data manager10,
  12. Chloe Donohue, clinical trials coordinator10,
  13. Mark Pritchard, specialty registrar in public health medicine11,
  14. Latifa B Patel, specialist registrar in paediatric respiratory medicine12,
  15. Shamez Ladhani, reader in paediatric infectious disease13 14,
  16. Louise Sigfrid, clinical research fellow15,
  17. Ian P Sinha, consultant physician in paediatric respiratory medicine and honorary senior clinical lecturer in child health3 12,
  18. Piero L Olliaro, professor of poverty related infectious diseases15,
  19. Jonathan S Nguyen-Van-Tam, professor of health protection16 17,
  20. Peter W Horby, professor of emerging infectious diseases15,
  21. Laura Merson, head of data and associate director15,
  22. Gail Carson, head of ISARIC global support centre15,
  23. Jake Dunning, head of emerging infections and zoonoses18 19,
  24. Peter J M Openshaw, professor of experimental medicine19,
  25. J Kenneth Baillie, academic consultant in critical care medicine20 21,
  26. Ewen M Harrison, professor of surgery and data science8,
  27. Annemarie B Docherty, senior clinical lecturer and honorary consultant in critical care8 21,
  28. Malcolm G Semple, professor of outbreak medicine and child health and consultant physician in paediatric respiratory medicine4 5
  29. on behalf of the ISARIC4C Investigators
    1. 1Department of Child Life and Health, University of Edinburgh, Edinburgh, UK
    2. 2Royal Hospital for Sick Children, Paediatric Infectious Diseases, Edinburgh, UK
    3. 3Women’s and Children’s Health, Institute of Translational Medicine, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK
    4. 4Respiratory Medicine, Alder Hey Children’s NHS Foundation Trust, Liverpool L12 2AP, UK
    5. 5Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK
    6. 6Infectious diseases Unit, Royal Liverpool University Hospital, Liverpool, UK
    7. 7Paediatric Infectious Diseases, Royal Hospital for Children, Glasgow, UK
    8. 8Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK
    9. 9Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, UK
    10. 10Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK
    11. 11Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
    12. 12Respiratory Medicine, Alder Hey Children’s Hospital, Liverpool, UK
    13. 13Immunisation and Countermeasures Division, Public Health England, Colindale, UK
    14. 14Paediatric Infectious Disease, St George’s Hospital, London, UK
    15. 15ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
    16. 16Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK
    17. 17United Kingdom Department of Health and Social Care, London, UK
    18. 18National Infection Service, Public Health England, [A: Where?]
    19. 19National Heart and Lung Institute, Imperial College London, London, UK
    20. 20Roslin Institute, University of Edinburgh, Edinburgh, UK
    21. 21Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, UK
    1. Correspondence to: M G Semple m.g.semple{at}liverpool.ac.uk (or @ProfCalumSemple on Twitter)
    • Accepted 17 August 2020

    Abstract

    Objective To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C).

    Design Prospective observational cohort study with rapid data gathering and near real time analysis.

    Setting 260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020).

    Participants 651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2.

    Main outcome measures Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C.

    Results Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 109/L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group.

    Conclusions Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive).

    Study registration ISRCTN66726260.

    Footnotes

    • Contributors: OVS, KAH, LS, PLO, JSN-V-T, PWH, LM, GC, WJD, PJMO, JKB, EMH, ABD, and MGS developed the concept of the study. SH, MG, LM, EMH, and ABD were responsible for data curation. OVS, LPo, CF, TMD, SS, CE, MGP, SL, IPS, EMH, ABD, and MGS analysed the data. JSN-V-T, PWH, GC, PJMO, JKB, ABD, and MGS obtained funding. OVS, KAH, LT, LP, SL, EMH, and ABD were involved in investigation. OVS, KAH, LT, LPo, SL, EMH, ABD, and MGS developed the methodology. KAH, LT, HH, SH, MG, CD, LPa, LS, and LM were responsible for administration. LS, PO, PWH, LM, and MGS coordinated resources. OVS, CF, TMD, SS, CE, and LM developed software. HH, SL, PO, JSN-V-T, LM, PJMO, JKB, ABD, and MGS provided supervision. KAH, LT, and LPo validated the data. OVS, CF, TMD, SS, CE, MGP, EMH, and ABD were involved in data visualisation. OVS, KAH, LT, LPo, SL, EMH, ABD, and MGS wrote the original draft of the manuscript. OVS, KAH, LT, LPo, CF, TMD, MGP, LPa, SL, IPS, JSN-V-T, JKB, EMH, ABD, and MGS reviewed and edited the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. MGS is the guarantor.

    • Funding: This work is supported by grants from the National Institute for Health Research (award CO-CIN-01) and the Medical Research Council (grant MC_PC_19059) and by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (NIHR award 200907), Wellcome Trust and Department for International Development (215091/Z/18/Z), and the Bill and Melinda Gates Foundation (OPP1209135). Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). JSN-V-T is seconded to the Department of Health and Social Care, England (DHSC). The views expressed are those of the authors and not necessarily those of the DHSC, DID, NIHR, MRC, Wellcome Trust, or PHE.

    • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the National Institute for Health Research and the Medical Research Council; JSN-V-T received grants from the Department of Health and Social Care, England, during the conduct of the study; PWH received grants from the Wellcome Trust, Department for International Development, and Bill and Melinda Gates Foundation and from NIHR during the conduct of the study; PJMO received personal fees from consultancy and grants from MRC, grants from EU Grant, grants from NIHR Biomedical Research Centre, grants from MRC/GSK, grants from Wellcome Trust, grants from NIHR (HPRU), grants from NIHR Senior Investigator, personal fees from European Respiratory Society, and grants from MRC Global Challenge Research Fund, outside the submitted work, and although the role of president of the British Society for Immunology was an unpaid appointment, travel and accommodation at some meetings is provided by the society; AMD received grants from Department of Health and Social Care, during the conduct of the study, and grants from Wellcome Trust outside the submitted work; JKB received grants from DHSC National Institute of Health Research UK, Medical Research Council UK, Wellcome Trust, Fiona Elizabeth Agnew Trust, Intensive Care Society, and Chief Scientist Office, during the conduct of the study; MGS received grants from DHSC National Institute of Health Research UK, Medical Research Council UK, and Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, during the conduct of the study, and from Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work; no other relationships or activities that could appear to have influenced the submitted work.

    • Ethical approval: Ethical approval was given by the South Central - Oxford C Research Ethics Committee in England (ref 13/SC/0149), the Scotland A Research Ethics Committee (ref 20/SS/0028), and the WHO Ethics Review Committee (RPC571 and RPC572, 25 April 2013).

    • Data sharing: The Independent Data and Material Access Committee welcomes applications for access to data and materials (https://isaric4c.net).

    • Transparency: The lead author (the manuscript's guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

    • Dissemination to participants and related patient and public communities: ISARIC4C has a public facing website and twitter account (@CCPUKstudy). We are engaging with print and internet press, television, radio, news, and documentary programme makers. We will explore distribution of findings with The Asthma UK and British Lung Foundation Partnership and take advice from NIHR Involve and GenerationR Alliance Young People’s Advisory Groups.

    • Provenance and peer review: Not commissioned; externally peer reviewed.

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