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Multisystem inflammatory syndrome in children: an Umbrella review

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Abstract

We conducted an Umbrella review of eligible studies to evaluate what patient features have been investigated in the multisystem inflammatory syndrome in children (MIS-C) population, in order to guide future investigations. We comprehensively searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from December 1, 2019 to the May 6, 2022. The time period was limited to cover the coronavirus disease-2019 (COVID-19) pandemic period. The protocol was registered in the PROSPERO registry (CRD42022340228). Eligible studies included (1) a study population of pediatric patients ≤21 years of age diagnosed with MIS-C; (2) an original Systematic review or Mata-analysis; (3) published 2020 afterward; and (4) was published in English. A total of 41 studies met inclusion criteria and underwent qualitative analysis. 28 studies reported outcome data of MIS-C. 22 studies selected clinical features of MIS-C, and 6 studies chose demographic data as a main topic. The mortality rate for children with MIS-C was 1.9% (interquartile range (IQR) 0.48), the ICU admission rate was 72.6% (IQR 8.3), and the extracorporeal membrane oxygenation rate was 4.7% (IQR 2.0). A meta-analysis of eligible studies found that cerebral natriuretic peptide in children with MIS-C was higher than that in children with COVID-19, and that the use of intravenous immunoglobulin (IVIG) in combination with glucocorticoids to treat MIS-C compared to IVIG alone was associated with lower treatment failure. In the future, for patients with MIS-C, studies focused on safety of surgery requiring general anesthesia, risk factors, treatment, and long-term outcomes are warranted.

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References

  1. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, Newburger JW, Kleinman LC, Heidemann SM, Martin AA, Singh AR, Li S, Tarquinio KM, Jaggi P, Oster ME, Zackai SP, Gillen J, Ratner AJ, Walsh RF, Fitzgerald JC, Keenaghan MA, Alharash H, Doymaz S, Clouser KN, Giuliano JS Jr, Gupta A, Parker RM, Maddux AB, Havalad V, Ramsingh S, Bukulmez H, Bradford TT, Smith LS, Tenforde MW, Carroll CL, Riggs BJ, Gertz SJ, Daube A, Lansell A, Coronado Munoz A, Hobbs CV, Marohn KL, Halasa NB, Patel MM, Randolph AG, Overcoming COVID-19 Investigators, CDC COVID-19 Response Team. Multisystem inflammatory syndrome in us children and adolescents. N Engl J Med. 2020;383:334–46.

    Article  CAS  PubMed  Google Scholar 

  2. Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, Barranco MA, Maxted AM, Rosenberg ES, Easton D, Udo T, Kumar J, Pulver W, Smith L, Hutton B, Blog D, Zucker H, New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. 2020;383:347–58.

    Article  CAS  PubMed  Google Scholar 

  3. Davies P, Evans C, Kanthimathinathan HK, Lillie J, Brierley J, Waters G, Johnson M, Griffiths B, du Pré P, Mohammad Z, Deep A, Playfor S, Singh D, Inwald D, Jardine M, Ross O, Shetty N, Worrall M, Sinha R, Koul A, Whittaker E, Vyas H, Scholefield BR, Ramnarayan P. Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study. Lancet Child Adolesc Health. 2020;4:669–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, Ramnarayan P, Fraisse A, Miller O, Davies P, Kucera F, Brierley J, McDougall M, Carter M, Tremoulet A, Shimizu C, Herberg J, Burns JC, Lyall H, Levin M, PIMS-TS Study Group and EUCLIDS and PERFORM Consortia. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA. 2020;21(324):259–69.

    Article  Google Scholar 

  5. Fernandes DM, Oliveira CR, Guerguis S, Eisenberg R, Choi J, Kim M, Abdelhemid A, Agha R, Agarwal S, Aschner JL, Avner JR, Ballance C, Bock J, Bhavsar SM, Campbell M, Clouser KN, Gesner M, Goldman DL, Hammerschlag MR, Hymes S, Howard A, Jung HJ, Kohlhoff S, Kojaoghlanian T, Lewis R, Nachman S, Naganathan S, Paintsil E, Pall H, Sy S, Wadowski S, Zirinsky E, Cabana MD, Herold BC, Tri-State Pediatric COVID-19 Research Consortium. Severe acute respiratory syndrome coronavirus 2 clinical syndromes and predictors of disease severity in hospitalized children and youth. J Pediatr. 2021;230:23–31.

    Article  CAS  PubMed  Google Scholar 

  6. Antúnez-Montes OY, Escamilla MI, Figueroa-Uribe AF, Arteaga-Menchaca E, Lavariega-Saráchaga M, Salcedo-Lozada P, Melchior P, de Oliveira RB, Tirado Caballero JC, Redondo HP, Montes Fontalvo LV, Hernandez R, Chavez C, Campos F, Uribe F, Del Aguila O, Rios Aida JA, Buitrago AP, Betancur Londoño LM, Mendoza Vega LF, Hernández CA, Sali M, Higuita Palacio JE, Gomez-Vargas J, Yock-Corrales A, Buonsenso D. COVID-19 and multisystem inflammatory syndrome in Latin American children: a multinational study. Pediatr Infect Dis J. 2021;40:e1–6.

    Article  PubMed  Google Scholar 

  7. Gai N, Maynes JT, Aoyama K. Unique challenges in pediatric anesthesia created by COVID-19. J Anesth. 2021;35:345–50.

    Article  PubMed  Google Scholar 

  8. Aoyama K, Heath A, Yang A, Maynes JT, Petroz G, Robertson J, Mc Donnell C, Velummailum R, Bond E, Pechlivanoglou P. Estimating the risk of SARS-CoV-2 transmission to pediatric anesthesiologists: a microsimulation model. Can J Anaesth. 2020;67:1694–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shioji N, Aoyama K, Englesakis M, Annich G, Maynes JT. Multisystem inflammatory syndrome in children during the coronavirus disease pandemic of 2019: a review of clinical features and acute phase management. J Anesth. 2021;35:563–70.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cochrane handbook for systematic reviews of interventions | cochrane training. Available from: https://training.cochrane.org/handbook. Cited 14 May 2022.

  11. Eden J, Levit L, Berg A, Morton S. Finding what works in health care: standards for systematic reviews. 2011. Available from: http://www.nap.edu/catalog.php?record_id=13059. Cited 14 May 2022.

  12. Centre for Reviews and Dissemination U of Y. CRD’s guidance on systematic reviews. Centre for Reviews Dissemination, University of York, 2008. 2009. p 294. Available from: https://gate2.library.lse.ac.uk/login?url=http://onlinelibrary.wiley.com. Cited 21 Apr 2023.

  13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19. Available from: https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19. Cited 21 Apr 2023.

  15. Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C) | CDC. Available from: https://www.cdc.gov/mis-c/hcp/. Cited 12 Jan 2021.

  16. Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (spring 2021 update) | Canadian Paediatric Society. Available from: https://cps.ca/en/documents/position/pims. Cited 21 Apr 2023.

  17. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS)—guidance for clinicians | RCPCH. Available from: https://www.rcpch.ac.uk/resources/paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19-pims-guidance. Cited 12 Jan 2021.

  18. Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, Moher D, Tugwell P, Welch V, Kristjansson E, Henry DA. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358: j4008.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Whiting P, Savović J, Higgins JP, Caldwell DM, Reeves BC, Shea B, Davies P, Kleijnen J, Churchill R. ROBIS: a new tool to assess risk of bias in systematic reviews was developed. J Clin Epidemiol. 2016;69:225–34.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Harwood R, Yan H, Talawila Da Camara N, Smith C, Ward J, Tudur-Smith C, Linney M, Clark M, Whittaker E, Saatci D, Davis PJ, Luyt K, Draper ES, Kenny SE, Fraser LK, Viner RM. Which children and young people are at higher risk of severe disease and death after hospitalisation with SARS-CoV-2 infection in children and young people: a systematic review and individual patient meta-analysis. eClinicalMedicine. 2022;44:101287.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Rodriguez-Gonzalez M, Castellano-Martinez A, Cascales-Poyatos HM, Perez-Reviriego AA. Cardiovascular impact of COVID-19 with a focus on children: a systematic review. World J Clin Cases. 2020;8:5250–83.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Haghighi Aski B, Manafi Anari A, Abolhasan Choobdar F, Zareh Mahmoudabadi R, Sakhaei M. Cardiac abnormalities due to multisystem inflammatory syndrome temporally associated with Covid-19 among children: a systematic review and meta-analysis. Int J Cardiol Heart Vasc. 2021;33: 100764.

    PubMed  PubMed Central  Google Scholar 

  23. Henrina J, Putra ICS, Lawrensia S, Marta DS, Wijaya E, Saboe A, Cool CJ, Suciadi LP. Cardiac manifestations, treatment characteristics, and outcomes of paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2: a systematic review. Prog Pediatr Cardiol. 2021;63: 101365.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Nepal G, Shrestha GS, Rehrig JH, Gajurel BP, Ojha R, Agrawal A, Panthi S, Khatri B, Adhikari I. Neurological Manifestations of COVID-19 Associated multi-system inflammatory syndrome in children: a systematic review and meta-analysis. J Nepal Health Res Counc. 2021;19:10–8.

    Article  PubMed  Google Scholar 

  25. Rouva G, Vergadi E, Galanakis E. Acute abdomen in multisystem inflammatory syndrome in children: a systematic review. Acta Paediatr. 2022;111:467–72.

    Article  CAS  PubMed  Google Scholar 

  26. Lo TC, Chen YY. Ocular and systemic manifestations in paediatric multisystem inflammatory syndrome associated with COVID-19. J Clin Med. 2021;10:2953.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Nascimento RB, Araujo NS, Silva JC, Xavier FCA. Oral manifestations of multisystemic inflammatory syndrome in children (MIS-C) and Kawasaki disease associated to COVID-19: a systematic review. Spec Care Dentist. 2022;42:266–80.

    Article  PubMed  Google Scholar 

  28. Yasuhara J, Watanabe K, Takagi H, Sumitomo N, Kuno T. COVID-19 and multisystem inflammatory syndrome in children: a systematic review and meta-analysis. Pediatr Pulmonol. 2021;56:837–48.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Abrams JY, Godfred-Cato SE, Oster ME, Chow EJ, Koumans EH, Bryant B, Leung JW, Belay ED. Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2: a systematic review. J Pediatr. 2020;226:45–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Guimarães D, Pissarra R, Reis-Melo A, Guimarães H. Multisystem inflammatory syndrome in children (MISC): a systematic review. Int J Clin Pract. 2021;75: e14450.

    Article  PubMed  Google Scholar 

  31. Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr. 2021;180:2019–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dhar D, Dey T, Samim MM, Padmanabha H, Chatterjee A, Naznin P, Chandra SR, Mallesh K, Shah R, Siddiqui S, Pratik K, Ameya P, Abhishek G. Systemic inflammatory syndrome in COVID-19-SISCoV study: systematic review and meta-analysis. Pediatr Res. 2022;91:1334–49.

    Article  CAS  PubMed  Google Scholar 

  33. Mardi P, Esmaeili M, Iravani P, Abdar ME, Pourrostami K, Qorbani M. Characteristics of children With Kawasaki disease-like signs in COVID-19 pandemic: a systematic review. Front Pediatr. 2021;9: 625377.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zhao Y, Yin L, Patel J, Tang L, Huang Y. The inflammatory markers of multisystem inflammatory syndrome in children (MIS-C) and adolescents associated with COVID-19: a meta-analysis. J Med Virol. 2021;93:4358–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhao Y, Patel J, Huang Y, Yin L, Tang L. Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: a meta-analysis. Am J Emerg Med. 2021;49:62–70.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zhou C, Zhao Y, Wang X, Huang Y, Tang X, Tang L. Laboratory parameters between multisystem inflammatory syndrome in children and Kawasaki disease. Pediatr Pulmonol. 2021;56:3688–98.

    Article  PubMed  Google Scholar 

  37. Wang Z, Zhao S, Tang Y, Wang Z, Shi Q, Dang X, Gan L, Peng S, Li W, Zhou Q, Li Q, Mafiana JJ, Cortés RG, Luo Z, Liu E, Chen Y. Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review. Eur J Pediatr. 2022;181:2135–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rauniyar R, Mishra A, Kharel S, Giri S, Rauniyar R, Yadav S, Chaudhary G. IVIG plus glucocorticoids versus IVIG alone in multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19: a systematic review and meta-analysis. Can J Infect Dis Med Microbiol. 2022;2022:9458653.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Llinás-Caballero K, Rodríguez Y, Fernández-Sarmiento J, Rodríguez-Jiménez M, Anaya JM. Kawasaki disease in Colombia: a systematic review and contrast with multisystem inflammatory syndrome in children associated with COVID-19. Rev Colomb Reumatol. 2022;29:S66–76.

    Google Scholar 

  40. De Rose DU, Pugnaloni F, Calì M, Ronci S, Caoci S, Maddaloni C, Martini L, Santisi A, Dotta A, Auriti C. Multisystem inflammatory syndrome in neonates born to mothers with SARS-CoV-2 infection (MIS-N) and in neonates and infants younger than 6 months with acquired COVID-19 (MIS-C): a systematic review. Viruses. 2022;14:750.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Sharma D, Bhaskar SMM. Prevalence of paediatric hyperinflammatory conditions in paediatric and adolescent hospitalized COVID-19 patients: a systematic review and meta-analysis. APMIS. 2022;130:101–10.

    Article  CAS  PubMed  Google Scholar 

  42. Karimi A, Ghafouri P, Alilou S, Rezaei N, Talesh SA, Ashraf H. Echocardiographic findings in multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19: a systematic review. Iran J Pediatr. 2022;32:e119001.

    Article  Google Scholar 

  43. O’loughlin L, Toledo NA, Budrie L, Waechter R, Rayner J. A systematic review of severe neurological manifestations in pediatric patients with coexisting sars-cov-2 infection. Neurol Int. 2021;13:410–27.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Zaffanello M, Piacentini G, Nosetti L, Ganzarolli S, Franchini M. Thrombotic risk in children with COVID-19 infection: a systematic review of the literature. Thromb Res. 2021;205:92–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Harrison SL, Buckley BJR, Rivera-Caravaca JM, Zhang J, Lip GYH. Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews. Eur Hear J Qual Care Clin Outcomes. 2021;7:330–9.

    Google Scholar 

  46. Treskova-Schwarzbach M, Haas L, Reda S, Pilic A, Borodova A, Karimi K, Koch J, Nygren T, Scholz S, Schönfeld V, Vygen-Bonnet S, Wichmann O, Harder T. Pre-existing health conditions and severe COVID-19 outcomes: an umbrella review approach and meta-analysis of global evidence. BMC Med. 2021;19:212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Yang L, Li J, Wei W, Yi C, Pu Y, Zhang L, Cui T, Ma L, Zhang J, Koyner J, Zhao Y, Fu P. Kidney health in the COVID-19 pandemic: an umbrella review of meta-analyses and systematic reviews. Front Public Health. 2022;10: 963667.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Shioji N, Sumie M, Aoyama K. How long elective surgery should be delayed from COVID-19 infection in pediatric patients? J Anesth. 2023. https://doi.org/10.1007/s00540-023-03284-3.

    Article  PubMed  Google Scholar 

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Acknowledgements

KA acknowledges the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Hospital for Sick Children, for secured academic time to conduct the current work as a recipient of a Merit Award. All authors acknowledge Mr. Alan Yang, SickKids Research Institute, for his statistical advice.

Funding

This work was supported by Outcomes Research Award 2021–2022 (KA), Department of Anesthesia and Pain Medicine, Hospital for Sick Children, Canadian Anesthesiologists’ Society Research Award 2022–2024 (KA) and Project Grants (PJX179857, PJT183603) 2022–2024, Canadian Institutes of Health Research (KA).

Author information

Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital, Tokyo, Japan

    Naohiro Shioji

  2. Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, 555 University Ave, #2211, Toronto, ON, M5G 1X8, Canada

    Makoto Sumie, Jason T. Maynes & Kazuyoshi Aoyama

  3. Program in Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Canada

    Makoto Sumie & Kazuyoshi Aoyama

  4. Department of Anesthesiology, St. Mary’s Hospital, Fukuoka, Japan

    Makoto Sumie

  5. Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Makoto Sumie

  6. Library and Information Services, University Health Network, Toronto, Canada

    Marina Englesakis

  7. Department of Critical Care Medicine, The Hospital for Sick Children, Toronto, Canada

    Elaine Gilfoyle

  8. Program in Molecular Medicine, SickKids Research Institute, Toronto, ON, Canada

    Jason T. Maynes

Authors
  1. Naohiro Shioji
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  2. Makoto Sumie
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  3. Marina Englesakis
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  4. Elaine Gilfoyle
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  5. Jason T. Maynes
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  6. Kazuyoshi Aoyama
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Contributions

KA and NS conceived this paper. KA and NS developed the protocol. ME performed the systematic literature searches, managed database results and documentation. NS, MS and KA performed the systematic review and data extraction. NS and KA performed the analysis on the result of the literature search and extracted data. NS and KA wrote the initial draft of the manuscript, and MS, GE and MJ helped draft the final version, which was approved by all authors.

Corresponding author

Correspondence to Kazuyoshi Aoyama.

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Shioji, N., Sumie, M., Englesakis, M. et al. Multisystem inflammatory syndrome in children: an Umbrella review. J Anesth (2024). https://doi.org/10.1007/s00540-024-03323-7

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