Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 6, 2020; 8(21): 5250-5283
Published online Nov 6, 2020. doi: 10.12998/wjcc.v8.i21.5250
Cardiovascular impact of COVID-19 with a focus on children: A systematic review
Moises Rodriguez-Gonzalez, Ana Castellano-Martinez, Helena Maria Cascales-Poyatos, Alvaro Antonio Perez-Reviriego
Moises Rodriguez-Gonzalez, Pediatric Cardiology Division, Puerta del Mar University Hospital, Cadiz 11009, Spain
Moises Rodriguez-Gonzalez, Ana Castellano-Martinez, Biomedical Research and Innovation Institute of Cadiz, Puerta del Mar University Hospital, Cadiz 11009, Spain
Ana Castellano-Martinez, Pediatric Nephrology Division, Puerta del Mar University Hospital, Cadiz 11009, Spain
Helena Maria Cascales-Poyatos, Pediatrics Division, Motril-San Antonio Primary Care Center, Motril 18600, Spain
Alvaro Antonio Perez-Reviriego, Pediatrics Division, UGC Pediatria AG Sur Granada, Santa Ana Hospital, Motril 18600, Spain
Author contributions: All the authors participated in the search of evidence and revision of the articles selected; Rodriguez-Gonzalez M designed the review, made the statistical analysis and wrote the first draft of the manuscript; Perez-Reviriego AA, Castellano-Martinez A and Cascales-Poyatos HM revised the first draft of the manuscript; Perez-Reviriego AA and Cascales-Poyatos HM summarized data on the tables of the final manuscript; Castellano-Martinez A made the figure of the final manuscript. 
Conflict-of-interest statement: Authors declare no conflict of interest for this article.
PRISMA 2009 Checklist statement: A PRISMA checklist was used to guide the development of the systematic review.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Moises Rodriguez-Gonzalez, MD, Doctor, Pediatric Cardiology Division, Puerta del Mar University Hospital, 21, Ana de Viya Avenue, Cadiz 11009, Spain. doctormoisesrodriguez@gmail.com
Received: September 1, 2020
Peer-review started: September 1, 2020
First decision: September 13, 2020
Revised: September 16, 2020
Accepted: October 13, 2020
Article in press: October 13, 2020
Published online: November 6, 2020
Processing time: 66 Days and 6.1 Hours
Abstract
BACKGROUND

Since the beginning of the pandemic, coronavirus disease-2019 (COVID-19) in children has shown milder cases and a better prognosis than adults. Although the respiratory tract is the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cardiovascular involvement is emerging as one of the most significant and life-threatening complications of SARS-CoV-2 infection in adults.

AIM

To summarize the current knowledge about the potential cardiovascular involvement in pediatric COVID-19 in order to give a perspective on how to take care of them during the current pandemic emergency.

METHODS

Multiple searches in MEDLINE, PubMed were performed using the search terms “COVID-19” or “SARS-CoV-2" were used in combination with “myocardial injury” or "arrhythmia" or “cardiovascular involvement” or "heart disease" or "congenital heart disease" or “pulmonary hypertension” or "long QT" or “cardiomyopathies” or “channelopathies” or "Multisystem inflammatory system" or "PMIS" or “MIS-C” or ”Pediatric multisystem inflammatory syndrome" or "myocarditis" or "thromboembolism to identify articles published in English language from January 1st, 2020 until July 31st, 2020. The websites of World Health Organization, Centers for Disease control and Prevention, and the Johns Hopkins Coronavirus Resource Center were reviewed to provide up to date numbers and infection control recommendations. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts concerning the subject were reviewed by the authors, and the data were extracted using a standardized collection tool. Data were subsequently analyzed with descriptive statistics. For Pediatric multisystemic inflammatory syndrome temporally associated with COVID-19 (PMIS), multiple meta-analyses were conducted to summarize the pooled mean proportion of different cardiovascular variables in this population in pseudo-cohorts of observed patients.

RESULTS

A total of 193 articles were included. Most publications used in this review were single case reports, small case series, and observational small-sized studies or literature reviews. The meta-analysis of 16 studies with size > 10 patients and with complete data about cardiovascular involvement in children with PMIS showed that PMIS affects mostly previously healthy school-aged children and adolescents presenting with Kawasaki disease-like features and multiple organ failure with a focus on the heart, accounting for most cases of pediatric COVID-19 mortality. They frequently presented cardiogenic shock (53%), ECG alterations (27%), myocardial dysfunction (52%), and coronary artery dilation (15%). Most cases required PICU admission (75%) and inotropic support (57%), with the rare need for extracorporeal membrane oxygenation (4%). Almost all of these children wholly recovered in a few days, although rare deaths have been reported (2%). Out of PMIS cases we identified 10 articles reporting sporadic cases of myocarditis, pulmonary hypertension and cardiac arrythmias in previously healthy children. We also found another 10 studies reporting patients with pre-existing heart diseases. Most cases consisted in children with severe COVID-19 infection with full recovery after intensive care support, but cases of death were also identified. The management of different cardiac conditions are provided based on current guidelines and expert panel recommendations.

CONCLUSION

There is still scarce data about the role of cardiovascular involvement in COVID-19 in children. Based on our review, children (previously healthy or with pre-existing heart disease) with acute COVID-19 requiring hospital admission should undergo a cardiac workup and close cardiovascular monitoring to identify and treat timely life-threatening cardiac complications.

Keywords: COVID-19; SARS-CoV-2; Congenital heart diseases; Myocardial dysfunction; Pediatric Multisystem Inflammatory Syndrome; Cardiac Biomarkers

Core Tip: Cardiovascular involvement has emerged as a remarkable risk-factor for poor outcomes of primary respiratory diseases such as coronavirus disease-2019 (COVID-19). Nevertheless, the body of evidence of cardiac complications in pediatric COVID-19 is still scarce to extract definitive conclusions about the adequate management for these patients. This review establishes a perspective on how COVID-19 impacts on the heart of both previously healthy children and those with pre-existing heart diseases, and how to take care of them during the current pandemic emergency.