Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 16, 2022; 10(29): 10435-10450
Published online Oct 16, 2022. doi: 10.12998/wjcc.v10.i29.10435
Age-adjusted NT-proBNP could help in the early identification and follow-up of children at risk for severe multisystem inflammatory syndrome associated with COVID-19 (MIS-C)
Moises Rodriguez-Gonzalez, Ana Castellano-Martinez
Moises Rodriguez-Gonzalez, Division of Pediatric Cardiology, Puerta del Mar University Hospital, Cadiz 11009, Spain
Ana Castellano-Martinez, Division of Pediatric Nephrology, Puerta del Mar University Hospital, Cadiz 11009, Spain
Author contributions: Rodriguez-Gonzalez M and Castellano-Martinez A collected the data, performed the statistical analysis, and wrote the manuscript; Both authors have read and approved the final manuscript.
Institutional review board statement: As retrospective data were collected from clinical reviews only, consent from patients and parents or guardians was not obtained. As the data analysis was retrospective and no additional data were collected beyond those required for standard medical care, a full ethics review was not required.
Informed consent statement: As retrospective data in this study were collected from clinical reviews only, consent from patients and parents or guardians was not obtained.
Conflict-of-interest statement: We have no financial relationships or any other conflict of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Ana Castellano-Martinez, MD, Doctor, Research Scientist, Division of Pediatric Nephrology, Puerta del Mar University Hospital, Ana de Viya Avenue 21st, Cadiz 11009, Spain.
Received: March 24, 2022
Peer-review started: March 24, 2022
First decision: June 16, 2022
Revised: June 17, 2022
Accepted: September 1, 2022
Article in press: September 1, 2022
Published online: October 16, 2022

Multisystem inflammatory syndrome in children (MIS-C) has emerged as a new disease associated with COVID-19 that presents in acute critically ill children with acute cardiovascular dysfunction.


To determine whether the age-adjusted N-terminal pro-brain natriuretic peptide (NT-proBNP) value (Z-log-NT-proBNP) is associated with severe MIS-C and myocardial dysfunction.


A retrospective study was conducted which included children with MIS-C managed at our institution between April 1, 2020, and February 28, 2022. We divided the population into groups depending on severity based on pediatric intensive care unit (PICU) admission. We compared Z-log-NT-proBNP values across these groups and analyzed Z-log-NT-proBNP dynamics during the one-month follow-up.


We included 17 participants [median age 3 (2-9) years] and seven (41%) required PICU admission. All (100%) of these cases presented very high (Z-log > 4) levels of NT-proBNP at the time of admission compared to only 5 (50%) patients with non-severe MIS-C (P = 0.025). NT-proBNP was significantly correlated with high-sensitive Troponin I levels (P = 0.045), Ross modified score (P = 0.003) and left ventricle ejection fraction (P = 0.021).


Raised NT-proBNP, specifically very high values (Z-log-NT-proBNP > 4) could help in the early identification of MIS-C patients with myocardial dysfunction requiring inotropic support and PICU admission.

Keywords: Multisystem inflammatory syndrome associated with COVID-19, COVID-19, SARS-CoV-2, NT-proBNP, Echocardiography, Myocardial dysfunction, Children

Core Tip: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition associated with coronavirus disease 2019 in which the cardiovascular system is frequently impaired, with more than half of children presenting with heart failure and myocardial dysfunction secondary to the inflammatory response. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a promising biomarker for the detection of cardiac dysfunction in conditions where heart failure and inflammation coexist, but its use in pediatrics is limited by its strong age-dependency. Therefore, we think that the use of age-adjusted NT-proBNP values could help to identify those children with risk for severe MIS-C.