Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19

Author:

Walton Mollie1,Raghuveer Geetha1,Harahsheh Ashraf2,Portman Michael A.3,Lee Simon4,Khoury Michael5,Dahdah Nagib6,Fabi Marianna7,Dionne Audrey8,Harris Tyler H.9,Choueiter Nadine10,Garrido-Garcia Luis Martin11,Jain Supriya12,Dallaire Frédéric13,Misra Nilanjana14,Hicar Mark D.15,Giglia Therese M.16,Truong Dongngan T.17,Tierney Elif Seda Selamet18,Thacker Deepika19,Nowlen Todd T.20,Szmuszkovicz Jacqueline R.21,Norozi Kambiz22,Orr William B.23,Farid Pedrom24,Manlhiot Cedric25,McCrindle Brian W.24,Alsalehi Mahmoud24,Ballweg Jean A.24,Barnes Benjamin T.24,Braunlin Elizabeth24,Buffone Ashley6,Bustamante-Ogando Juan Carlos26,Chang Arthur J.15,Corral Nicolas10,Cowles Heather12,Dancey Paul27,de Ferranti Sarah D8,Ganzoury Mona El28,Elias Matthew16,Elsamman Nora28,Cooke Elisa Fernández29,Goldenberg Guillermo Larios30,Grcic Michelle M.4,Harris Kevin C.31,Jone Pei-Ni32,Kajimoto Hidemi3,Khare Manaswitha33,Kutty Shelby25,Lanari Marcello7,Mauriello Daniel34,McHugh Kimberly E.35,Merves Shae A.36,Mohandas Sindhu21,Mondal Tapas37,Pagano Joseph J.5,Prasad Deepa38,Ravi Prasad38

Affiliation:

1. Children's Mercy Hospital

2. Children's National Hospital, The George Washington University School of Medicine & Health Sciences

3. Seattle Children's Research Institute

4. The Heart Center at Nationwide Children's Hospital

5. University of Alberta

6. Centre Hospitalier Universitaire Sainte-Justine

7. Pediatric Emergency Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy

8. Boston Children's Hospital

9. Children's Hospital of Pittsburgh

10. Children's Hospital at Montefiore

11. Hospital Angeles Lomas, Huixquilucan, Mexico & Instituto Nacional de Pediatría, Mexico City, Mexico

12. Maria Fareri Children's Hospital

13. Centre Hospitalier Universitaire de Sherbrooke

14. Cohen Children's Medical Center

15. University at Buffalo, State University of New York

16. Children's Hospital of Philadelphia

17. Primary Children's Hospital

18. Stanford University

19. Nemours Children's Hospital, Wilmington, DE, USA

20. Phoenix Children's Hospital

21. Children's Hospital of Los Angeles

22. Western University

23. Washington University in St. Louis

24. Hospital for Sick Children

25. Johns Hopkins University

26. Hospital Angeles Lomas, Huixquilucan, Mexico

27. Janeway Children's Health and Rehabilitation Centre

28. Ain Shams University

29. Hospital Universitario 12 de Octubre

30. Pontificia Universidad Católica de Chile

31. British Columbia Children's Hospital

32. Children's Hospital Colorado

33. Rady Children's Hospital-San Diego

34. Johns Hopkins All Children's Hospital

35. Medical University of South Carolina

36. University of Arkansas for Medical Sciences

37. McMaster University

38. Banner Children's at Desert Medical Center, Mesa, AZ, USA

Abstract

Abstract Background: Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. Methods: The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide(NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Results: Higher NTproBNP (>1500 ng/L) and TnI (>20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89% respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Conclusions: Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

Publisher

Research Square Platform LLC

Reference30 articles.

1. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association;McCrindle BW;Circulation,2017

2. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association;Newburger JW;Circulation,2004

3. Multisystem Inflammatory Syndrome in Children in New York State;Dufort EM;N Engl J Med,2020

4. Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19;Feldstein LR;JAMA,2021

5. Organization WH (2020) Multisystem Inflammatory Syndrome in Children and Adolescents with COVID-19. May 15 2020 [cited 2023 January 1]; Scientific Brief]. Available from: https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19

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