Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Original article

Vol. 153 No. 10 (2023)

Cardiac involvement in children with paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): data from a prospective nationwide surveillance study

  • Anita Uka
  • Sabrina Bressieux-Degueldre
  • Michael Buettcher
  • Lisa Kottanattu
  • Margerita Plebani
  • Anita Niederer-Loher
  • Nina Schöbi
  • Michael Hofer
  • Julie Tomasini
  • Johannes Trück
  • Reto Villiger
  • Noémie Wagner
  • Daniela Wuetz
  • Nicole Ritz
  • Petra Zimmermann
DOI
https://doi.org/10.57187/smw.2023.40092
Cite this as:
Swiss Med Wkly. 2023;153:40092
Published
13.10.2023

Summary

BACKGROUND: Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) may occur 4 to 8 weeks after SARS-CoV-2 infection. The acute presentation of PIMS-TS has been well described, but data on longer-term outcomes, particularly cardiac, is scarce.

METHODS: This prospective nationwide surveillance study included children and adolescents less than 18 years of age who were hospitalised with PIMS-TS in Switzerland between March 2020 and March 2022. Data was collected from all 29 paediatric hospitals through the Swiss Paediatric Surveillance Unit (SPSU) during hospitalisation and approximately six weeks after discharge. The data was analysed after categorising the participants into three groups based on their admission status to the intensive care unit (ICU) (non-ICU, ICU-moderate) and the requirement for invasive ventilatory and/or inotropic support (ICU-severe).

RESULTS: Overall, 204 children were included of whom 194 (95.1%) had follow-up data recorded. Median age was 9.0 years (interquartile range [IQR] 6.0–11.5) and 142 (69.6%) were male. In total, 105/204 (51.5%) required ICU admission, of whom 55/105 (52.4%) received inotropic support and 14/105 (13.3%) mechanical ventilation (ICU-severe group). Echocardiography was performed in 201/204 (98.5%) children; 132 (64.7%) had a cardiac abnormality including left ventricular systolic dysfunction (73 [36.3%]), a coronary artery abnormality (45 [22.4%]), pericardial effusion (50 [24.9%]) and mitral valve regurgitation (60 [29.9%]). Left ventricular systolic dysfunction was present at admission in 62/201 (30.8%) children and appeared during hospitalisation in 11 (5.5%) children. A coronary artery abnormality was detected at admission in 29/201 (14.2%) children and developed during hospitalisation or at follow-up in 13 (6.5%) and 3 (1.5%) children, respectively. None of the children had left ventricular systolic dysfunction at follow-up, but a coronary abnormality and pericardial effusion were found in 12 (6.6%) and 3 (1.7%) children, respectively. School absenteeism at the time of follow-up was more frequent in children who had been admitted to the ICU (2.5% in the non-ICU group compared to 10.4% and 17.6% in the ICU-moderate and ICU-severe group, respectively) (p = 0.011).

CONCLUSION: Cardiac complications in children presenting with PIMS-TS are common and may worsen during the hospitalisation. Irrespective of initial severity, resolution of left ventricular systolic dysfunction is observed, often occurring rapidly during the hospitalisation. Most of the coronary artery abnormalities regress; however, some are still present at follow-up, emphasising the need for prolonged cardiac evaluation after PIMS-TS.

References

  1. Roarty C, Waterfield T. Review and future directions for PIMS-TS (MIS-C). Arch Dis Child 2022;0:archdischild-2021-323143. doi:10.1136/archdischild-2021-323143 DOI: https://doi.org/10.1136/archdischild-2021-323143
  2. Jiang L, Tang · Kun, Irfan O, et al. Epidemiology, Clinical Features, and Outcomes of Multisystem Inflammatory Syndrome in Children (MIS-C) and Adolescents-a Live Systematic Review and Meta-analysis. Curr Pediatr Rep. 2022;1:3. 10.1007/s40124-022-00264-1 DOI: https://doi.org/10.1007/s40124-022-00264-1
  3. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MB, et al.; Overcoming COVID-19 Investigators; CDC COVID-19 Response Team. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 2020 Jul;383(4):334–46. 10.1056/nejmoa2021680 10.1056/NEJMoa2021680
  4. Radia T, Williams N, Agrawal P, Harman K, Weale J, Cook J, et al. Multi-system inflammatory syndrome in children & adolescents (MIS-C): A systematic review of clinical features and presentation. Paediatr Respir Rev. 2021 Jun;38:51–7. 10.1016/j.prrv.2020.08.001 DOI: https://doi.org/10.1016/j.prrv.2020.08.001
  5. Flood J, Shingleton J, Bennett E, et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020. Lancet Reg Heal - Eur 2021;3:100075. doi:10.1016/j.lanepe.2021.100075 DOI: https://doi.org/10.1016/j.lanepe.2021.100075
  6. Santos MO, Gonçalves LC, Silva PA, et al. Multisystem inflammatory syndrome (MIS-C): a systematic review and meta-analysis of clinical characteristics, treatment, and outcomes. J Pediatr (Rio J). 2021;: 10.1016/j.jped.2021.08.006
  7. Schlapbach LJ, Andre MC, Grazioli S, Schöbi N, Ritz N, Aebi C, et al.; PIMS-TS working group of the Interest Group for Pediatric Neonatal Intensive Care (IGPNI) of the Swiss Society of Intensive Care and the Pediatric Infectious Diseases Group Switzerland (PIGS). Best Practice Recommendations for the Diagnosis and Management of Children With Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS; Multisystem Inflammatory Syndrome in Children, MIS-C) in Switzerland. Front Pediatr. 2021 May;9:667507. 10.3389/fped.2021.667507
  8. Uka A, Buettcher M, Bernhard-Stirnemann S, et al. Factors Associated with Hospital and Intensive Care Admission in Paediatric SARS-CoV-2 Infection: A Prospective Nationwide Observational Cohort Study. Eur J Pediatr Published Online First; 2021. 10.1007/s00431-021-04276-9 DOI: https://doi.org/10.2139/ssrn.3823127
  9. Zimmermann P, Uka A, Buettcher M, et al. Neonates with SARS-CoV-2 infection: spectrum of disease from a prospective nationwide observational cohort study. 2022. doi:10.4414/smw.2022.w30185 10.4414/SMW.2022.w30185 DOI: https://doi.org/10.4414/SMW.2022.w30185
  10. Harris PA, Taylor R, Thielke R, et al. Research Electronic Data Capture (REDCap)-A metadata-driven methodology and workflow process for providing translational research informatics support. doi:10.1016/j.jbi.2008.08.010 DOI: https://doi.org/10.1016/j.jbi.2008.08.010
  11. Nir A, Lindinger A, Rauh M, Bar-Oz B, Laer S, Schwachtgen L, et al. NT-pro-B-type natriuretic peptide in infants and children: reference values based on combined data from four studies. Pediatr Cardiol. 2009 Jan;30(1):3–8. 10.1007/s00246-008-9258-4 DOI: https://doi.org/10.1007/s00246-008-9258-4
  12. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al.; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention. Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation. 2017 Apr;135(17):e927–99. 10.1161/CIR.0000000000000484/FORMAT/EPUB 10.1161/CIR.0000000000000484 DOI: https://doi.org/10.1161/CIR.0000000000000484
  13. Dallaire F, Dahdah N. New equations and a critical appraisal of coronary artery Z scores in healthy children. J Am Soc Echocardiogr. 2011 Jan;24(1):60–74. 10.1016/j.echo.2010.10.004 DOI: https://doi.org/10.1016/j.echo.2010.10.004
  14. Welzel T, Schöbi N, André MC, Bailey DG, Blanchard-Rohner G, Buettcher M, et al.; Swissped Recovery Trial. Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS): protocol of the Swissped RECOVERY Trial. Front Pediatr. 2022 May;10:905046. 10.3389/fped.2022.905046 DOI: https://doi.org/10.3389/fped.2022.905046
  15. Valverde I, Singh Y, Sanchez-de-Toledo J, Theocharis P, Chikermane A, Di Filippo S, et al.; AEPC COVID-19 Rapid Response Team*. Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe. Circulation. 2021 Jan;143(1):21–32. 10.1161/CIRCULATIONAHA.120.050065
  16. Belay ED, Abrams J, Oster ME, et al. Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic Editorial Supplemental content. Published Online First: 2021. doi:10.1001/jamapediatrics.2021.0630 DOI: https://doi.org/10.1001/jamapediatrics.2021.0630
  17. Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al.; 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 Jul;324(3):259–69. 10.1001/jama.2020.10369
  18. Mannarino S, Raso I, Garbin M, Ghidoni E, Corti C, Goletto S, et al. Cardiac dysfunction in Multisystem Inflammatory Syndrome in Children: an Italian single-center study. Ital J Pediatr. 2022 Feb;48(1):25. 10.1186/s13052-021-01189-z DOI: https://doi.org/10.1186/s13052-021-01189-z
  19. Hejazi OI, Loke YH, Harahsheh AS. Short-term Cardiovascular Complications of Multi-system Inflammatory Syndrome in Children (MIS-C) in Adolescents and Children. Curr Pediatr Rep. 2021;9(4):93–103. 10.1007/s40124-021-00258-5 DOI: https://doi.org/10.1007/s40124-021-00258-5
  20. 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 May;56(5):837–48. 10.1002/ppul.25245 DOI: https://doi.org/10.1002/ppul.25245
  21. Caro-Patón GL, de Azagra-Garde AM, García-Salido A, Cabrero-Hernández M, Tamariz A, Nieto-Moro M. Shock and Myocardial Injury in Children With Multisystem Inflammatory Syndrome Associated With SARS-CoV-2 Infection: What We Know. Case Series and Review of the Literature. J Intensive Care Med. 2021 Apr;36(4):392–403. 10.1177/0885066620969350 DOI: https://doi.org/10.1177/0885066620969350
  22. Minocha PK, Phoon CK, Verma S, Singh RK. Cardiac Findings in Pediatric Patients With Multisystem Inflammatory Syndrome in Children Associated With COVID-19. Clin Pediatr (Phila). 2021 Feb;60(2):119–26. 10.1177/0009922820961771 DOI: https://doi.org/10.1177/0009922820961771
  23. Theocharis P, Wong J, Pushparajah K, Mathur SK, Simpson JM, Pascall E, et al. Multimodality cardiac evaluation in children and young adults with multisystem inflammation associated with COVID-19. Eur Heart J Cardiovasc Imaging. 2021 Jul;22(8):896–903. 10.1093/ehjci/jeaa212 DOI: https://doi.org/10.1093/ehjci/jeaa212
  24. Ramcharan T, Nolan O, Chui ·, et al. Paediatric Inflammatory Multisystem Syndrome: Temporally Associated with SARS-CoV-2 (PIMS-TS): Cardiac Features, Management and Short-Term Outcomes at a UK Tertiary Paediatric Hospital. 2020;41:1391–401. doi:10.1007/s00246-020-02391-2 DOI: https://doi.org/10.1007/s00246-020-02391-2
  25. Das N, Hill R, Trivedi M, et al. Longitudinal Assessment of Cardiac Function Following Multisystem Inflammatory Syndrome in Children Associated with COVID-19. Pediatr Cardiol Published Online First. 2022 Jul;21: 10.1007/S00246-022-02972-3 10.1007/s00246-022-02972-3
  26. Nelson MC, Mrosak J, Hashemi S, Manos C, Prahalad S, Varghese S, et al. Delayed Coronary Dilation with Multisystem Inflammatory Syndrome in Children. CASE (Phila). 2021 Sep;6(1):31–5. 10.1016/j.case.2021.08.002 DOI: https://doi.org/10.1016/j.case.2021.08.002
  27. Capone CA, Misra N, Ganigara M, et al. Six Month Follow-up of Patients With Multi-System Inflammatory Syndrome in Children. doi:10.1542/peds.2021-050973 DOI: https://doi.org/10.1542/peds.2021-050973
  28. Sanil Y, Misra A, Safa R, Blake JM, Eddine AC, Balakrishnan P, et al. Echocardiographic Indicators Associated with Adverse Clinical Course and Cardiac Sequelae in Multisystem Inflammatory Syndrome in Children with Coronavirus Disease 2019. J Am Soc Echocardiogr. 2021 Aug;34(8):862–76. 10.1016/j.echo.2021.04.018 DOI: https://doi.org/10.1016/j.echo.2021.04.018
  29. Aziz OA, Sadiq M, Qureshi AU, et al. Short to midterm follow-up of multi-system inflammatory syndrome in children with special reference to cardiac involvement. Cardiol Young Published Online First; 2022. 10.1017/S1047951122000828 DOI: https://doi.org/10.1017/S1047951122000828
  30. Stasiak A, Kędziora P, Kierzkowska B, Niewiadomska-Jarosik K, Perdas E, Smolewska E. Changes in the cardiovascular system in children with pediatric multisystem inflammatory syndrome temporally associated with COVID-19 - A single center experience. Int J Cardiol. 2022 Aug;361:126–33. 10.1016/j.ijcard.2022.05.030 DOI: https://doi.org/10.1016/j.ijcard.2022.05.030
  31. Yildirim Arslan S, Sahbudak Bal Z, Bayraktaroglu S, et al. Cardiac Assessment in Children with MIS-C: Late Magnetic Resonance Imaging Features. Pediatr Cardiol. •••;1:3. 10.1007/s00246-022-02977-y
  32. Feldstein LR, Tenforde MW, Friedman KG, Newhams M, Rose EB, Dapul H, et al.; Overcoming COVID-19 Investigators. Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19. JAMA. 2021 Mar;325(11):1074–87. 10.1001/JAMA.2021.2091 10.1001/jama.2021.2091
  33. Muniz JC, Dummer K, Gauvreau K, Colan SD, Fulton DR, Newburger JW. Coronary artery dimensions in febrile children without Kawasaki disease. Circ Cardiovasc Imaging. 2013 Mar;6(2):239–44. 10.1161/CIRCIMAGING.112.000159/FORMAT/EPUB 10.1161/CIRCIMAGING.112.000159 DOI: https://doi.org/10.1161/CIRCIMAGING.112.000159
  34. Noval Rivas M, Arditi M. Kawasaki disease: pathophysiology and insights from mouse models. doi:10.1038/s41584-020-0426-0 DOI: https://doi.org/10.1038/s41584-020-0426-0
  35. Wong J, Theocharis P, Regan W, Pushparajah K, Stephenson N, Pascall E, et al. Medium-Term Cardiac Outcomes in Young People with Multi-system Inflammatory Syndrome: the Era of COVID-19. Pediatr Cardiol. 2022 Dec;43(8):1728–36. 10.1007/s00246-022-02907-y DOI: https://doi.org/10.1007/s00246-022-02907-y
  36. Chakraborty A, Johnson JN, Spagnoli J, et al. Long-Term Cardiovascular Outcomes of Multisystem Inflammatory Syndrome in Children Associated with COVID-19 Using an Institution Based Algorithm. ;1:3. doi:10.1007/s00246-022-03020-w DOI: https://doi.org/10.1007/s00246-022-03020-w
  37. Alsaied T, Tremoulet AH, Burns JC, Saidi A, Dionne A, Lang SM, et al. Review of Cardiac Involvement in Multisystem Inflammatory Syndrome in Children. Circulation. 2021 Jan;143(1):78–88. 10.1161/CIRCULATIONAHA.120.049836 DOI: https://doi.org/10.1161/CIRCULATIONAHA.120.049836
  38. Harahsheh AS, Krishnan A, Debiasi RL, et al. Cardiac echocardiogram findings of severe acute respiratory syndrome coronavirus-2-associated multi-system inflammatory syndrome in children. Cardiol Young Published Online First; 2021. 10.1017/S1047951121003024 DOI: https://doi.org/10.1017/S1047951121003735
  39. Sirico D, Basso A, Sabatino J, et al. Evolution of echocardiographic and cardiac magnetic resonance imaging abnormalities during follow-up in patients with multisystem inflammatory syndrome in children. Eur Hear J - Cardiovasc Imaging Published Online First: 21 July 2022. doi:10.1093/ehjci/jeac096 DOI: https://doi.org/10.1093/ehjci/jeac096
  40. Abrams JY, Oster ME, Godfred-Cato SE, Bryant B, Datta SD, Campbell AP, et al. Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study. Lancet Child Adolesc Health. 2021 May;5(5):323–31. 10.1016/S2352-4642(21)00050-X DOI: https://doi.org/10.1016/S2352-4642(21)00050-X
  41. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, et al. Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic. Circulation. 2020 Aug;142(5):429–36. 10.1161/CIRCULATIONAHA.120.048360 DOI: https://doi.org/10.1161/CIRCULATIONAHA.120.048360
  42. Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al.; 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 Jul;324(3):259–69. 10.1001/jama.2020.10369 DOI: https://doi.org/10.1001/jama.2020.10369
  43. Dionne A, Mah DY, Son MB, Lee PY, Henderson L, Baker AL, et al. Atrioventricular Block in Children With Multisystem Inflammatory Syndrome. Pediatrics. 2020 Nov;146(5):e2020009704. 10.1542/peds.2020-009704 DOI: https://doi.org/10.1542/peds.2020-009704
  44. Carmona CA, Levent F, Lee K, et al. Case Report Atrioventricular Conduction Abnormalities in Multisystem Inflammatory Syndrome in Children. Published Online First; 2021. 10.1155/2021/6124898 DOI: https://doi.org/10.1155/2021/6124898
  45. Schlapbach LJ, Andre MC, Grazioli S, Schöbi N, Ritz N, Aebi C, et al.; PIMS-TS working group of the Interest Group for Pediatric Neonatal Intensive Care (IGPNI) of the Swiss Society of Intensive Care and the Pediatric Infectious Diseases Group Switzerland (PIGS). Best Practice Recommendations for the Diagnosis and Management of Children With Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS; Multisystem Inflammatory Syndrome in Children, MIS-C) in Switzerland. Front Pediatr. 2021 May;9:667507. 10.3389/fped.2021.667507 DOI: https://doi.org/10.3389/fped.2021.667507
  46. Ouldali N, Toubiana J, Antona D, Javouhey E, Madhi F, Lorrot M, et al.; French Covid-19 Paediatric Inflammation Consortium. Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children. JAMA. 2021 Mar;325(9):855–64. 10.1001/jama.2021.0694 DOI: https://doi.org/10.1001/jama.2021.0694
  47. Chowdhury D, Fremed MA, Dean P, Glickstein JS, Robinson J, Rellosa N, et al. Return to Activity After SARS-CoV-2 Infection: Cardiac Clearance for Children and Adolescents. Sports Health. 2022;14(4):460–5. 10.1177/19417381211039746 DOI: https://doi.org/10.1177/19417381211039746

Most read articles by the same author(s)

<< < 1 2 3