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Cardiac Arrhythmias in Pediatric Age: Are They Triggered by SARS-CoV-2 Infection?

Authors:

Abstract

Coronavirus disease 2019 is a highly contagious infectious disease. Research on heart rhythm disorders in children affected by COVID-19 infection is quite lacking. An infant and a congenital heart disease (CHD) teenager with a pacemaker presented fascicular tachycardia and atrial flutter, respectively, during COVID-19 pauci-symptomatic infection. The hemodynamic condition was always stable. The self-resolving trend of the atrial flutter and progressive resolution of the ventricular tachycardia occurred in conjunction with the negativization of the swab. These particular tachyarrhythmias have been reported as a form of potential arrhythmic complication during active pauci-symptomatic COVID-19 infection for the first time ever.
Citation: Fumanelli, J.; Sabatino, J.;
Biffanti, R.; Reffo, E.; Di Salvo, G.;
Leoni, L. Cardiac Arrhythmias in
Pediatric Age: Are They Triggered by
SARS-CoV-2 Infection? COVID 2023,
3, 192–197. https://doi.org/10.3390/
covid3020014
Academic Editor: Giuseppe Novelli
Received: 8 December 2022
Revised: 25 January 2023
Accepted: 30 January 2023
Published: 3 February 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Case Report
Cardiac Arrhythmias in Pediatric Age: Are They Triggered by
SARS-CoV-2 Infection?
Jennifer Fumanelli 1, * , Jolanda Sabatino 1, Roberta Biffanti 1, Elena Reffo 1, Giovanni Di Salvo 1
and Loira Leoni 2
1Pediatric Cardiology Unit, Woman’s and Child’s Health Department, Padua University, 35122 Padova, Italy
2Cardiology Unit, Department of Cardiac Thoracic Vascular Sciences and Public Health, Padua Hospital
University Padua, 35128 Padova, Italy
*Correspondence: jennifer.fumanelli@aopd.veneto.it; Tel.: +39-3476912734
Abstract:
Coronavirus disease 2019 is a highly contagious infectious disease. Research on heart
rhythm disorders in children affected by COVID-19 infection is quite lacking. An infant and a
congenital heart disease (CHD) teenager with a pacemaker presented fascicular tachycardia and atrial
flutter, respectively, during COVID-19 pauci-symptomatic infection. The hemodynamic condition
was always stable. The self-resolving trend of the atrial flutter and progressive resolution of the
ventricular tachycardia occurred in conjunction with the negativization of the swab. These particular
tachyarrhythmias have been reported as a form of potential arrhythmic complication during active
pauci-symptomatic COVID-19 infection for the first time ever.
Keywords:
SARS-CoV-2; COVID-19 infection; arrhythmias; posterior left fascicular tachycardia;
congenital heart disease; atrial flutter; amiodarone
1. Introduction
Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease that
is widespread worldwide. COVID-19 has multiorgan consequences with subsequent
outcomes of varying severity.
Our worldwide knowledge about this new virus is mostly based on studies in adults,
which demonstrate aftermaths of the virus on the respiratory system, but there are many
hemodynamic complications and electrophysiologic abnormalities as well. Some reports
and one review describe life-threatening arrhythmias as a potential severe complication in
COVID-19 adult patients, especially patients who suffer from pre-existing heart disease
(such as inherited arrhythmias syndrome) and other comorbidities, such as renal failure, hy-
pertension, diabetes, acute respiratory distress syndrome (ARDS), or cancer [
1
3
]. Hypoxia,
electrolyte imbalances, and the hyper-inflammatory response (IL-6, TNF-
α
, IL-1) are risk
factors for the ion K+ and Ca+ channel dysfunction, which can lead to the onset of arrhyth-
mias, especially ventricular arrhythmias from simple premature ventricular contractions
(PVCs) up to Torsades de Pointes or ventricular fibrillation. Up to now, literature regarding
the heart rhythm disorders in pediatric patients affected by COVID-19 infection has been
quite lacking. Mostly, pediatric studies report the most frequent arrhythmic involvement
during multisystem inflammatory syndrome in children; in particular, 7–60% of patients
have cardiac rhythm disorders, which include aspecific repolarization abnormalities, QTc
prolongation, first- and second atrio-ventricular block, premature ventricular contractions
and premature atrial contractions, supraventricular tachyarrhythmias (especially atrial
fibrillation), and non-sustained ventricular tachyarrhythmias [
4
]. On the contrary, acute
pediatric COVID-19 infections are usually asymptomatic and mild and healthy children
generally do not develop severe cardiac manifestations [
5
]. As a matter of fact, they tend to
have less life-threatening arrhythmias, such as premature ventricular contractions, prema-
ture atrial contractions, incomplete right bundle branch block, first degree atrio-ventricular
COVID 2023,3, 192–197. https://doi.org/10.3390/covid3020014 https://www.mdpi.com/journal/covid
COVID 2023,3193
block, or supraventricular tachycardias [
6
]. One study reports a very low percent of mild
electrophysiological involvement (12% of repolarization abnormalities and mild PR prolon-
gation) in non-hospitalized children with asymptomatic mild COVID-19 infection [
7
]. These
mild heart rhythm disorders then spontaneously resolved over time. Another worldwide
study reports 15% of arrhythmic complications in a huge hospitalized pediatric population
without further details about the type or severity of arrhythmias [8].
A past medical history of congenital heart disease (CHD), bronchopulmonary disease,
immune system deficiency, and hemoglobinopathies are considered to be predisposing
factors for the development of severe cardiac manifestations, both hemodynamic (acute
heart failure, myo-pericarditis) and arrhythmic cases [
9
]. Rare case reports describe the
association and the outcome between CHD and arrhythmias or between healthy children
and severe arrhythmias.
In this study, we report two unusual COVID-19-related arrhythmic cases that were
collected from March 2020 to October 2021 by our tertiary referral center.
2. Case Presentation
2.1. Case 1
A 10-month-old baby presented to the pediatric emergency department with irritabil-
ity and inconsolable crying for 24 h without other symptoms, including fever or either
respiratory or gastrointestinal involvement. Upon his arrival, the infant had stable hemody-
namic condition with normal blood pressure for age, but the heart rhythm was tachycardic.
No heart murmurs or pericardial rubs were found. Additionally, no respiratory pathologi-
cal noises or gastrointestinal pathological signs were detected. On the electrocardiogram,
sustained ventricular tachycardia was found at 220 beats per minute (bpm) (Figure 1). An
echocardiogram was performed, which showed no congenital heart disease, ventricular
dysfunction, or coronary dilatation. The baby had no family history of sudden death or
rhythm disorders.
COVID 2023, 2, FOR PEER REVIEW 2
healthy children generally do not develop severe cardiac manifestations [5]. As a matter
of fact, they tend to have less life-threatening arrhythmias, such as premature ventricular
contractions, premature atrial contractions, incomplete right bundle branch block, first
degree atrio-ventricular block, or supraventricular tachycardias [6]. One study reports a
very low percent of mild electrophysiological involvement (12% of repolarization abnor-
malities and mild PR prolongation) in non-hospitalized children with asymptomatic mild
COVID-19 infection [7]. These mild heart rhythm disorders then spontaneously resolved
over time. Another worldwide study reports 15% of arrhythmic complications in a huge
hospitalized pediatric population without further details about the type or severity of ar-
rhythmias [8].
A past medical history of congenital heart disease (CHD), bronchopulmonary dis-
ease, immune system deficiency, and hemoglobinopathies are considered to be predispos-
ing factors for the development of severe cardiac manifestations, both hemodynamic
(acute heart failure, myo-pericarditis) and arrhythmic cases [9]. Rare case reports describe
the association and the outcome between CHD and arrhythmias or between healthy chil-
dren and severe arrhythmias.
In this study, we report two unusual COVID-19-related arrhythmic cases that were
collected from March 2020 to October 2021 by our tertiary referral center.
2. Case Presentation
2.1. Case 1
A 10-month-old baby presented to the pediatric emergency department with irrita-
bility and inconsolable crying for 24 h without other symptoms, including fever or either
respiratory or gastrointestinal involvement. Upon his arrival, the infant had stable hemo-
dynamic condition with normal blood pressure for age, but the heart rhythm was tachy-
cardic. No heart murmurs or pericardial rubs were found. Additionally, no respiratory
pathological noises or gastrointestinal pathological signs were detected. On the electro-
cardiogram, sustained ventricular tachycardia was found at 220 beats per minute (bpm)
(Figure 1). An echocardiogram was performed, which showed no congenital heart dis-
ease, ventricular dysfunction, or coronary dilatation. The baby had no family history of
sudden death or rhythm disorders.
Figure 1. Posterior left fascicular tachycardia (left axis deviation with RBBB).
The pre-admission nasopharyngeal swab was positive for COVID-19 with all the
other blood exams negative, especially inflammatory tests (C-reactive protein) and tro-
ponin. The serology for SARS-CoV-2 demonstrated high antibody titer for IgM (6797
Figure 1. Posterior left fascicular tachycardia (left axis deviation with RBBB).
The pre-admission nasopharyngeal swab was positive for COVID-19 with all the other
blood exams negative, especially inflammatory tests (C-reactive protein) and troponin.
The serology for SARS-CoV-2 demonstrated high antibody titer for IgM (6797 kU/L).
Continuous intravenous therapy with amiodarone was started, which was effective even if
COVID 2023,3194
there were still some paroxysms of tachycardia in the following four days. The intravenous
antiarrhythmic therapy was gradually matched with oral somministration up to the total
oral administration of amiodarone.
The arrhythmia was overall well controlled without recurrence of ventricular tach-
yarrhythmia. Another echocardiography was performed after 5 days, showing normal
systolic and diastolic biventricular function with normal size of coronary arteries. The
patient was discharged in good condition with stable sinus rhythm after 21 days of recovery
on oral antiarrhythmic therapy with amiodarone (7 mg/kg/die three times per day).
2.2. Case 2
A 16-year-old teenager with surgically corrected congenital heart disease (atrio-
ventricular septal defect (AVSD) and a dual chamber pacemaker for post-surgical complete
AV block reported palpitations in the two days preceding access to the pediatric emergency
department. Remote control of the device at the beginning of symptoms showed the onset
of atrial flutter from 2 days before; this supraventricular tachyarrhythmia has been never
detected at the previous periodic PM controls in telemedicine.
Upon arrival at the emergency department, the patient presented stable hemodynamic
condition and was completely asymptomatic; the EKG confirmed an atrial flutter 2:1 at the
heart rate of 120 bpm (Figure 2).
COVID 2023, 2, FOR PEER REVIEW 3
kU/L). Continuous intravenous therapy with amiodarone was started, which was effec-
tive even if there were still some paroxysms of tachycardia in the following four days. The
intravenous antiarrhythmic therapy was gradually matched with oral somministration up
to the total oral administration of amiodarone.
The arrhythmia was overall well controlled without recurrence of ventricular tach-
yarrhythmia. Another echocardiography was performed after 5 days, showing normal
systolic and diastolic biventricular function with normal size of coronary arteries. The pa-
tient was discharged in good condition with stable sinus rhythm after 21 days of recovery
on oral antiarrhythmic therapy with amiodarone (7 mg/kg/die three times per day).
2.2. Case 2
A 16-year-old teenager with surgically corrected congenital heart disease (atrio-ven-
tricular septal defect (AVSD) and a dual chamber pacemaker for post-surgical complete
AV block reported palpitations in the two days preceding access to the pediatric emer-
gency department. Remote control of the device at the beginning of symptoms showed
the onset of atrial flutter from 2 days before; this supraventricular tachyarrhythmia has
been never detected at the previous periodic PM controls in telemedicine.
Upon arrival at the emergency department, the patient presented stable hemody-
namic condition and was completely asymptomatic; the EKG confirmed an atrial flutter
2:1 at the heart rate of 120 bpm (Figure 2).
Figure 2. Atrial flutter 2:1.
The pre-admission nasopharyngeal swab was positive for COVID-19, with all the
other blood exams negative. C-reactive protein, the other inflammation tests, and troponin
were negative. An echocardiogram was performed without signs of enlargement of both
atria or valve insufficiency, ventricular dysfunction, or coronary dilatation.
Anticoagulant therapy with subcutaneous heparin was started without considering
an antiarrhythmic therapy, but the pacemaker was reprogrammed (DDIR 75–160 bpm) by
obtaining a median heart rate of 80 bpm with persistent heart rhythm disorder.
After 15 days of quarantine, the nasopharyngeal swab was negative. Remote control
of the device showed the spontaneous restoration of the sinus rhythm in correspondence
with the negativization of the swab (Figure 3). No further supraventricular arrhythmias
were detected in the next short-term and medium-term follow-up.
Figure 2. Atrial flutter 2:1.
The pre-admission nasopharyngeal swab was positive for COVID-19, with all the
other blood exams negative. C-reactive protein, the other inflammation tests, and troponin
were negative. An echocardiogram was performed without signs of enlargement of both
atria or valve insufficiency, ventricular dysfunction, or coronary dilatation.
Anticoagulant therapy with subcutaneous heparin was started without considering
an antiarrhythmic therapy, but the pacemaker was reprogrammed (DDIR 75–160 bpm) by
obtaining a median heart rate of 80 bpm with persistent heart rhythm disorder.
After 15 days of quarantine, the nasopharyngeal swab was negative. Remote control
of the device showed the spontaneous restoration of the sinus rhythm in correspondence
with the negativization of the swab (Figure 3). No further supraventricular arrhythmias
were detected in the next short-term and medium-term follow-up.
COVID 2023,3195
COVID 2023, 2, FOR PEER REVIEW 4
Figure 3. Remote control of PM about FLA.
3. Discussion
Some previous studies and reviews have reported a correlation between electrophys-
iologic abnormalities and COVID-19 in children. Sharmeen et al. described a pediatric
population affected by COVID-19 infection with low prevalence of significant arrhyth-
mias (NSVT or AT) in normal heart [10]. One interesting and a rare case was described by
US colleagues [11]. During the acute phase of symptomatic COVID-19 infection, a 9-day-
old girl presented with aberrant supraventricular tachycardia, which was correctly diag-
nosed and then effectively treated by overdrive through a transesophageal pacing.
Up to now, no literature has described an atrial flutter in congenital heart disease
during a COVID-19 infection, especially in regard to pediatric population.
The only case report talks about an adult patient with a previously healthy heart who
had been affected by severe SARS-CoV-2 infection that was complicated by cardiovascu-
lar involvement, especially an arrhythmic one [12]. This patient presented an atrial flutter
with high ventricular response rate that further compromised the cardiac pump function
and the critical respiratory situation. The antiarrhythmic therapy failed, and catheter ab-
lation had to be performed, despite the patients critically ill condition. The procedure was
effective in terms of the stable restoration of sinus rhythm and respiratory conditions. Un-
like this case, we did not have to perform any medical therapy or invasive procedure dur-
ing the acute phase because the girl was completely asymptomatic both for cardiac hemo-
dynamic involvement and respiratory involvement, despite the cardiac heart disease. As
a matter of fact, the hypothesis of concomitant myocarditis was ruled out by analyzing
the primary data collected from cardiac objectivity, the negative blood test, and the nor-
mal biventricular function in both of the patients. The myocardial involvement during the
acute phase of SARS-CoV-2 infection is well known [13], but these two patients basically
had arrhythmic complications of the acute COVID-19 infection, which were then followed
by stable restoration of sinus rhythm.
For the first time, we recorded this type of supraventricular tachycardia as it occurred
spontaneously in a CHD pediatric patient with stable hemodynamic condition. This type
of tachyarrhythmia is typically related as a potential arrhythmic consequence during post-
surgical follow-up of this CHD; nevertheless, the hemodynamic instability has not been
previously reported in this case or from any other potential causes as well. The temporal
correlation between the duration of this supraventricular tachycardia and the microbio-
logical positivization might suggest the role of this virus as trigger factor of cardiac ar-
rhythmia.
The broad spectrum of ventricular tachyarrhythmias (VTs) has been already reported
as arrhythmic involvement which is related to hemodynamic deterioration in critical
Figure 3. Remote control of PM about FLA.
3. Discussion
Some previous studies and reviews have reported a correlation between electrophys-
iologic abnormalities and COVID-19 in children. Sharmeen et al. described a pediatric
population affected by COVID-19 infection with low prevalence of significant arrhythmias
(NSVT or AT) in normal heart [
10
]. One interesting and a rare case was described by US
colleagues [
11
]. During the acute phase of symptomatic COVID-19 infection, a 9-day-old
girl presented with aberrant supraventricular tachycardia, which was correctly diagnosed
and then effectively treated by overdrive through a transesophageal pacing.
Up to now, no literature has described an atrial flutter in congenital heart disease
during a COVID-19 infection, especially in regard to pediatric population.
The only case report talks about an adult patient with a previously healthy heart who
had been affected by severe SARS-CoV-2 infection that was complicated by cardiovascular
involvement, especially an arrhythmic one [
12
]. This patient presented an atrial flutter
with high ventricular response rate that further compromised the cardiac pump function
and the critical respiratory situation. The antiarrhythmic therapy failed, and catheter
ablation had to be performed, despite the patient’s critically ill condition. The procedure
was effective in terms of the stable restoration of sinus rhythm and respiratory conditions.
Unlike this case, we did not have to perform any medical therapy or invasive procedure
during the acute phase because the girl was completely asymptomatic both for cardiac
hemodynamic involvement and respiratory involvement, despite the cardiac heart disease.
As a matter of fact, the hypothesis of concomitant myocarditis was ruled out by analyzing
the primary data collected from cardiac objectivity, the negative blood test, and the normal
biventricular function in both of the patients. The myocardial involvement during the acute
phase of SARS-CoV-2 infection is well known [
13
], but these two patients basically had
arrhythmic complications of the acute COVID-19 infection, which were then followed by
stable restoration of sinus rhythm.
For the first time, we recorded this type of supraventricular tachycardia as it occurred
spontaneously in a CHD pediatric patient with stable hemodynamic condition. This type
of tachyarrhythmia is typically related as a potential arrhythmic consequence during
post-surgical follow-up of this CHD; nevertheless, the hemodynamic instability has not
been previously reported in this case or from any other potential causes as well. The
temporal correlation between the duration of this supraventricular tachycardia and the
COVID 2023,3196
microbiological positivization might suggest the role of this virus as trigger factor of
cardiac arrhythmia.
The broad spectrum of ventricular tachyarrhythmias (VTs) has been already reported
as arrhythmic involvement which is related to hemodynamic deterioration in critical
COVID-19 disease, but no fascicular tachycardia has been documented either in adult or in
pediatric populations.
Considering the quite rare manifestation of this VT during the first decade of life
of a healthy child, it is undoubtedly even rarer to record a fascicular tachycardia in a 10-
month-old baby with normal heart and stable hemodynamic condition.
This is the first time ever that this idiopathic ventricular tachycardia has been registered
in a healthy infant who also had a documented SARS-CoV-2 infection. Could the SARS-
CoV-2 infection really be a co-factor of fascicular tachycardia in this case?
We thought this might be a possibility, which is supported by the good control of the
heart rhythm on antiarrhythmic therapy after the negativization of the swab.
4. Conclusions
The worldwide literature about the correlation between pediatric cardiac arrhythmias
and COVID-19 is growing.
These particular tachyarrhythmias have been reported as potential arrhythmic compli-
cations during active pauci-symptomatic COVID-19 infection for the first time ever. The
self-resolving trend of the AFL and the progressive resolution of the fascicular tachycardia
occurred in conjunction with the negativization of the swab. Might it be only SARS-CoV-2
infection correlated? This could be a good hypothesis, but the long-term follow-up needs
to be studied.
5. Learning Objectives
5.1. Case 1: An Infant with Posterior Left Fascicular Tachycardia
1. To define the etiology of the fascicular tachycardia
2.
To understand the role of COVID-19 as a trigger factor of the ventricular tachycardia
5.2. Case 2: A CHD Patient with PMK and Atrial Flutter
1. To define the trigger mechanism of the supraventricular tachycardia
2.
To understand the time correlation between the arrhythmias and COVID-19 infection
Author Contributions:
Conceptualization: J.F.; methodology: J.F.; software: J.S. and J.F.; validation:
R.B., E.R., G.D.S. and L.L.; formal analysis: J.F. and J.S.; investigation: J.F.; resources: L.L. and J.F.;
data curation: J.F.; writing—original draft preparation: J.F.; writing—review and editing: J.S. and
L.L.; visualization: J.F.; supervision: J.S. and L.L.; project administration: J.F.; funding acquisition:
G.D.S. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: This study did not require ethical approval.
Informed Consent Statement:
Informed consent was obtained from all subjects involved in
the study.
Data Availability Statement:
Data was derived from the management system of patients at Chil-
dren’s Hospital, Pediatric Cardiology Unit, of Padua and the telemedicine monitoring system of
implanted devices.
Conflicts of Interest: The authors declare no conflict of interest.
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As the coronavirus 2019 (COVID-19) pandemic marches unrelentingly, more patients with cardiac arrhythmias are emerging due to the effects of the virus on the respiratory and cardiovascular (CV) systems and the systemic inflammation that it incurs, and also as a result of the proarrhythmic effects of COVID-19 pharmacotherapies and other drug interactions and the associated autonomic imbalance that enhance arrhythmogenicity. The most worrisome of all arrhythmogenic mechanisms is the QT prolonging effect of various anti-COVID pharmacotherapies that can lead to polymorphic ventricular tachycardia in the form of torsade des pointes and sudden cardiac death. It is therefore imperative to monitor the QT interval during treatment; however, conventional approaches to such monitoring increase the transmission risk for the staff and strain the health system. Hence, there is dire need for contactless monitoring and telemetry for inpatients, especially those admitted to the intensive care unit, as well as for outpatients needing continued management. In this context, recent technological advances have ushered in a new era in implementing digital health monitoring tools that circumvent these obstacles. All these issues are herein discussed and a large body of recent relevant data are reviewed.
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Current understanding of the impact of COVID-19 on arrhythmias continues to evolve as new data emerges. Cardiac arrhythmias are more common in critically ill COVID-19 patients. The potential mechanisms that could result in arrhythmogenesis among COVID-19 patients includes hypoxia caused by direct viral tissue involvement of lungs, myocarditis, abnormal host immune response, myocardial ischemia, myocardial strain, electrolyte derangements, intravascular volume imbalances and drug sides effects. To manage these arrhythmias, it is imperative to increase the awareness of potential drug-drug interactions, to monitor QTc prolongation while receiving COVID therapy and provide special considerations for patients with inherited arrhythmia syndromes. It is also crucial to minimize exposure to COVID-19 infection by stratifying the need for intervention and using telemedicine. As COVID-19 infection continues to prevail with a potential for future surges, more data is required to better understand pathophysiology and to validate management strategies.
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Background There is limited data regarding the electrophysiological abnormalities and arrhythmias in children with COVID-19, including those associated with treatment using potentially pro-arrhythmic Hydroxychloroquine (HCQ) and Azithromycin (AZN). Objectives To describe the electrophysiologic findings and arrhythmias associated with pediatric COVID-19 and its treatment. Methods A single center retrospective chart review was undertaken and included all patients with 1) symptoms of COVID-19, and 2) PCR (+) nasopharyngeal swabs for SARS-CoV-2 who were placed on continuous telemetry for the duration of their hospitalization during March through May, 2020. Results Thirty-six patients were included in the study. Significant arrhythmias were found in 6 (non-sustained (ns) ventricular tachycardia in 5 and sustained atrial tachycardia in 1). All were self-resolving and half prompted prophylactic anti-arrhythmic therapy. Patients with significant arrhythmias were likely to have non-cardiac co-morbidities (4/6), but these were not more common than in patients without arrhythmias (20/30, p=1). The use of HCQ with or without AZN was associated with statistically significant QTc prolongation (411+19 msec vs 426+15 msec, p<0.0001). QTc was not statistically different in patients with and without arrhythmias (425+15 msec vs 425+15 msec, p=1). Conclusions In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but more common than expected in a general pediatric population. Comorbidities are not more common in patients with arrhythmias than in patients without arrhythmias. COVID-19 treatment using HCQ is associated with QTc prolongation, but was not associated with arrhythmias in pediatric patients.