Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Multisystem inflammatory syndrome in children: a longitudinal perspective on risk factors and future directions

Pediatric Research volume 95, pages 15–17 (2024)Cite this article

Multisystem inflammatory syndrome in children (MIS-C) is a relatively rare, but potentially life-threatening, post-infectious phenomenon, with an incidence of 2 per 100,000 SARS-CoV-2 persons younger than 21 years previously infected with SARS-CoV-2.1 A significant proportion of children with MIS-C undergo rapid clinical deterioration, characterised by shock, systemic inflammation, and cardiac dysfunction.2,3,4 Despite the substantial morbidity, the majority of children make a full recovery and mortality rates are relatively low (1.7%).2 While most children who develop MIS-C are previously healthy, studies have shown that around 25% of these children have pre-existing co-morbidities, with obesity and asthma most commonly reported.5,6,7,8 Identifying predisposing and precipitating factors for MIS-C is crucial for identifying and protecting children at risk of developing MIS-C and its severe complications and may also be of relevance for future pandemics.

Auger et al. sought to address risk factors for MIS-C, Kawasaki disease (KD) and complications of COVID-19 infections by conducting a longitudinal cohort study using hospital discharge summary data from 1.2 million children and mothers in Quebec, Canada prior to and during the first year of the COVID-19 pandemic.9 This study is an exemplar of the potential utility of total population data to investigate risk factors, identify co-morbidities and gain a deeper understanding of the impact of relatively rare but important conditions, and also highlights some of the limitations of analyses of linked data. The results on the epidemiological and clinical features of MIS-C are in keeping with the current literature, with increased frequency in older children (5–12 years) and males, and a high proportion of cardiac complications, gastrointestinal involvement, and shock.2 Moreover, when compared to KD and paediatric COVID-19, children with MIS-C had a more severe disease phenotype with increased requirement for intensive care and longer hospital stay.3,7,10

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Dufort, E. M. et al. Multisystem inflammatory syndrome in children in New York State. N. Engl. J. Med. 383, 347–358 (2020).

    Article  CAS  PubMed  Google Scholar 

  2. Ahmed, M. et al. Multisystem inflammatory syndrome in children: a systematic review. EClinicalMedicine 26, 100527 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Whittaker, E. et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 324, 259–269 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Alsaied, T. et al. Review of cardiac involvement in multisystem inflammatory syndrome in children. Circulation 143, 78–88 (2021).

    Article  CAS  PubMed  Google Scholar 

  5. Belhadjer, Z. et al. Acute heart failure in multisystem inflammatory syndrome in children in the context of global SARS-CoV-2 pandemic. Circulation 142, 429–436 (2020).

    Article  CAS  PubMed  Google Scholar 

  6. Feldstein, L. R. et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N. Engl. J. Med. 383, 334–346 (2020).

    Article  CAS  PubMed  Google Scholar 

  7. Swann, O. V. et al. Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study. BMJ 370, m3249 (2020).

    Article  PubMed  Google Scholar 

  8. Harwood, R. et al. 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 44, 101287 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Auger, N. et al. Multisystem inflammatory syndrome in 1.2 million children: longitudinal cohort study of risk factors. Pediatr. Res. 1–9 https://doi.org/10.1038/s41390-023-02633-y (2023).

  10. Castagnoli, R. et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 174, 882–889 (2020).

    Article  PubMed  Google Scholar 

  11. Rhedin, S. et al. Risk factors for multisystem inflammatory syndrome in children – a population-based cohort study of over 2 million children. Lancet Reg. Health Eur. 19, 100443 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kompaniyets, L. Body mass index and risk for COVID-19–related hospitalization, intensive care unit admission, invasive mechanical ventilation, and death — United States, March–December 2020. MMWR Morb. Mortal. Wkly Rep. 70, 355–361 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Office for National Statistics (ONS). Obesity and mortality during the coronavirus (COVID-19) pandemic, England: 24 January 2020 to 30 August 2022 (ONS, 2022).

  14. Kwaifa, I. K., Bahari, H., Yong, Y. K. & Noor, S. M. Endothelial dysfunction in obesity-induced inflammation: molecular mechanisms and clinical implications. Biomolecules 10, 291 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Collier, F. et al. Innate immune activation and circulating inflammatory markers in preschool children. Front. Immunol. 12, 830049 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Schmidt, V., Hogan, A. E., Fallon, P. G. & Schwartz, C. Obesity-mediated immune modulation: one step forward, (Th)2 steps back. Front. Immunol. 13, 932893 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Andersen, C. J., Murphy, K. E. & Fernandez, M. L. Impact of obesity and metabolic syndrome on immunity. Adv. Nutr. 7, 66–75 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Webster, R. J. et al. Hospitalisation with infection, asthma and allergy in Kawasaki disease patients and their families: genealogical analysis using linked population data. PLoS One 6, e28004 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hoste, L., Van Paemel, R. & Haerynck, F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur. J. Pediatr. 180, 2019–2034 (2021).

  20. Channon-Wells, S. et al. Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study. Lancet Rheumatol. 5, e184–e199 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ranasinghe, L. et al. Global impact of COVID-19 on childhood tuberculosis: an analysis of notification data. Lancet Glob. Health 10, e1774–e1781 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Piccini, P., Montagnani, C. & de Martino, M. Gender disparity in pediatrics: a review of the current literature. Ital. J. Pediatr. 44, 1 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Stumper, A. et al. Pubertal status and age are differentially associated with inflammatory biomarkers in female and male adolescents. J. Youth Adolesc. 49, 1379–1392 (2020).

    Article  PubMed  Google Scholar 

  24. O’Keeffe, L. M. et al. Sex-specific trajectories of molecular cardiometabolic traits from childhood to young adulthood. Heart 109, 674–685 (2023).

    Article  PubMed  Google Scholar 

  25. Viner, R. & Booy, R. Epidemiology of health and illness. BMJ 330, 411–414 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bleyer, A., Viny, A. & Barr, R. Cancer in 15- to 29-year-olds by primary site. Oncologist 11, 590–601 (2006).

    Article  PubMed  Google Scholar 

  27. Wood, J. R. et al. Most youth with type 1 diabetes in the T1D exchange clinic registry do not meet American Diabetes Association or International Society for Pediatric and Adolescent Diabetes Clinical Guidelines. Diabetes Care 36, 2035–2037 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zambrano, L. D. et al. Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA vaccination against multisystem inflammatory syndrome in children among persons aged 12-18 years - United States, July-December 2021. MMWR Morb. Mortal. Wkly Rep. 71, 52–58 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Levy, M. et al. Multisystem inflammatory syndrome in children by COVID-19 vaccination status of adolescents in France. JAMA 327, 281–283 (2022).

    Article  CAS  PubMed  Google Scholar 

  30. Halasa, N. B. Effectiveness of maternal vaccination with mRNA COVID-19 vaccine during pregnancy against COVID-19–associated hospitalization in infants aged 6 months — 17 States, July 2021–January 2022. MMWR Morb. Mortal. Wkly Rep. 71, 264–270 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

HP is supported by the Diagnosis and Management of Febrile Illness using RNA Personalised Molecular Signature Diagnosis Study project grant. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 848196. EW is a co-investigator on the NIH-funded study: Diagnosing and Predicting Risk in Children with SARS-CoV-2-Related Illness, Project Number: R61HD105590-01. DB is supported by a National Health and Medical Research Council Investigator Grant (GTN1175744). Research at Murdoch Children’s Research Institute is supported by the Victorian Government’s Operational Infrastructure Support Program.

Author information

Authors and Affiliations

  1. Department of Infectious Disease, Section of Paediatrics, Imperial College, London, UK

    Harsita Patel & Elizabeth Whittaker

  2. Infection and Immunity Theme, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia

    David Burgner

  3. Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia

    David Burgner

  4. Paediatric Infectious Diseases, Imperial College Healthcare NHS Trust, London, UK

    Elizabeth Whittaker

Authors
  1. Harsita Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Burgner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elizabeth Whittaker
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HP: conceptualisation, writing—original draft, writing—review and editing. EW: conceptualisation, writing—original draft, writing—review and editing, supervision. DB: conceptualisation, writing—review and editing, supervision.

Corresponding author

Correspondence to David Burgner.

Ethics declarations

Competing interests

EW has provided investigator roles in relation to product development for AstraZeneca, Pfizer, Moderna, iLiAD and Sanofi with fees paid to Imperial College Healthcare NHS Trust. DB and HP report no conflicts of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patel, H., Burgner, D. & Whittaker, E. Multisystem inflammatory syndrome in children: a longitudinal perspective on risk factors and future directions. Pediatr Res 95, 15–17 (2024). https://doi.org/10.1038/s41390-023-02803-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02803-y

Search

Advanced search

Quick links