Cardiovascular Complications in Children Post COVID-19: A Systematic Review

Abstract

Cardiovascular involvements are one of the most important and threatening problems of SARS-CoV-2 infection and can cause a wide range of clinical manifestations in children. Therefore, a review of previous studies is necessary to prevent the occurrence of cardiovascular complications and reduce the risk of mortality in this age group of patients. To investigate the cardiovascular complications in children with COVID-19, international authoritative databases including PubMed, Scopus, Embase, Web of Science, Google Scholar, and Persian databases were searched using the main concepts, all articles were published between January 2020 and November 2022. According to the results of the present study, no deaths due to cardiovascular involvement were reported in the studied healthy children with COVID-19. In addition, in electrocardiogram (ECG) findings, supraventricular arrhythmias (SVA) and ventricular arrhythmias (VA) and in echo findings, left ventricular dysfunction (LVD) have had the most consequences.

INTRODUCTION

Severe acute respiratory infection syndrome coronavirus 2 (SARS-CoV2) was reported in China in late December 2019 and has been introduced as the causative agent of COVID-19. After a short time, this disease was announced as a pandemic by the World Health Organization (WHO) on March 21, 2020. SARS-CoV-2 virus from the coronavirus family enters the cells through the respiratory system of the angiotensin-converting enzyme (ACE) receptors present on the respiratory epithelium. Viral infections are widely recognized as one of the most common infectious causes of myocarditis.[1]

As it has been reported in Worldometers until December 2022, about 6 million deaths occurred worldwide, of which 0.4% were children. The initial reports of this disease revealed that a few cases of children were infected and less than 2% of hospitalized patients were children; it was supposed that children are immune from this disease or show mild symptoms.[2] However, with the prevalence of the disease and the further involvement of families and children, reports of severe and even fatal cases of the disease among children were published.[3] Moreover, it has been defined as a wide range of cardiovascular abnormalities.[4] Consequently, there are recently major concerns about severe manifestations in the age group of children.[5,6]

According to the results of the studies, the pathogenesis of post-SARS-CoV-2 infection cardiac involvement may reflect the process of viral replication and spread through respiratory blood and/or the lymphatic system. It appears that SARS-CoV-2 can lead to cardiac damage through several different mechanisms. For example, the SARS-CoV-2 virus uses ACE2 as a receptor to enter the cells.[7] This enzyme is expressed in the lungs widely as well as the heart and blood vessels. Some hypotheses suggest that SARS-CoV-2 binding changes the ACE2 expression or disrupts the renin–angiotensin–aldosterone system (RAAS).[7,8,9]

In addition, viral acute lung injury results in acute respiratory injury followed by severe hypoxia. This complication may lead to oxidative stress, endothelial cell loss, dysrhythmia, acute left ventricular dysfunction (LVD), and microvascular and myocardial damage due to an increased need for myocardial oxygen.[10,11,12,13,14,15]

Moreover, SARS-CoV-2 infection leads to facilitating the induction of endothelial cell inflammation as a result of viral involvement and the host's inflammatory response. Endothelial dysfunction is the main cause of microvascular dysfunction as it changes the vascular balance toward more vasoconstriction, inflammation with association of tissue edema, and procoagulant state and contributes to vascular thrombosis and ischemia in the next organ.[12,13,16,17]

In contrast, myocardial damage may be caused by certain drugs (antiviral drugs, antimalarial drugs, corticosteroids, monoclonal antibodies, and antibiotics), myocardial inflammation (myocardium inflammatory disease), or pericardial inflammation (stimulation or inflammation of the pericardial layers) along with viral infection as the most common cause.[18,19,20,21,22,23] Tachycardia might have multiple causes and manifest simultaneous symptoms, such as fever, shortness of breath, pain, and anxiety, and sinus tachycardia is usually without any other significant symptoms in an electrocardiogram (ECG).[24,25]

Children infected with SARS-CoV-2 may have a simultaneous infection with another viral agent.[24] In pericarditis, the range of myocarditis clinical manifestations can be from mild non-specific symptoms to chest pain or cardiogenic shock. It may manifest with flu-like symptoms, shortness of breath, tachycardia, nausea, and loss of appetite in children or poor feeding and tachycardia in infants.[22,23]

Considering that cardiovascular involvements (CI) are one of the most central and threatening problems of infection with SARS-CoV-2 and this disease can cause a wide range of clinical manifestations in children, it seems essential to review previous studies in this regard to avoid misdiagnosis of severe clinical cases, prevent the occurrence of cardiovascular complications (CC), such as myocardial damage, acute left ventricular dysfunction, heart failure, arrhythmia, or other cardiovascular disorders, and reduce the risk of mortality in this age group of patients. Therefore, acquaintances can be raised in this regard, careful monitoring and extensive preventive measures can be considered for these patients, and the risk of adverse consequences for children can be minimized. To meet the mentioned objectives, the present systematic review study aimed at investigating CC in children with COVID-19.

MATERIALS AND METHODS

This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta analyses (PRISMA) checklist,[26] and the protocol has been registered in PROSPERO (registration number CRD42022324446). Also, the code of ethics (approval code: IR.MUI.MED.REC.1401.120) was received from the Ethics Committee of Isfahan University of Medical Sciences.

Search strategy

Two independent authors comprehensively and independently conducted a complete and systematic search of the published studies from January 2020 until November 2022 in PubMed, Scopus, Embase, Web of Science, and Google Scholar as well as Persian databases such as SID and Magiran.

The search was performed using the keywords obtained from the Medical Subject Headings (MeSH) database and the keywords of other articles published in this field by combining AND, OR operators. The search was performed using the following keywords: “COVID-19,” “pediatric,” “children,” “infant,” “outcome,” “mortality,” “arrhythmia,” “heart failure,” “ventricular dysfunction,” “myocardial,” “myocarditis,” “SARS-CoV-2,” “coronavirus,” “left ventricular dysfunction,” “valvular disorders,” “coronary aneurysm,” “pulmonary hypertension,” “intracardiac thrombosis,” “arrhythmia and block,” “pericardial effusion,” “myocarditis,” and “pericarditis.”

Multiple searches were performed during the writing of this manuscript, as the COVID-19 pandemic is still evolving. An example of the search strategy in PubMed is as follows: (” COVID-19” OR “SARS-CoV-2” OR “coronavirus”) AND (“children” OR” infant” OR “pediatric”) AND (“heart failure” OR “arrhythmia” OR “ventricular dysfunction” OR “myocardial” OR “myocarditis” OR “valvular disorders” OR “coronary aneurysm” OR “pulmonary hypertension” OR “intracardiac thrombosis” OR “arrhythmia and block” OR “pericardial effusion” OR “myocarditis” OR “pericarditis”) AND” outcome “OR” mortality.”

Inclusion and exclusion criteria

The inclusion criteria consisted of all titles/abstracts of human studies including clinical trials, cross-sectional studies, cohort studies, case–control studies, case series, and case reports that were conducted on children under the age of 18 years, without having a previous history of cardiovascular diseases, with the aim of evaluating COVID-19-induced CC. In addition, conference abstracts and references of the presented articles were searched to find any relevant data to add to the review. In this study, only articles in the English language were included. Moreover, studies with non-randomized samples as well as studies having low qualities, that is, less than 50% score based on JADAD and CONSORT standard checklists for intervention studies (clinical trial) and a score of lower than 14 based on the Newcastle Ottawa Scale for cohort studies were excluded.

Selection process

In an initial search of electronic databases, 586 records were detected. After entering the records into the EndNote software and removing duplicates, 398 articles remained to be screened through title/abstract review by two members of the research team. Title/abstract screening resulted in 58 related records. In the final stage, 12 articles were included in the review after considering the inclusion/exclusion criteria.[27,28,29,30,31,32,33,34,35,36,37,38]

Risk of bias

The risk of bias in the included studies was addressed by two authors independently using the Cochrane risk-of-bias tool.[39] Possible disagreements were resolved in a panel discussion; otherwise, the issue was referred to a third reviewer. Reviewers independently determined biases in an article based on the conditions of random sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases. They were graded by writing yes (low risk of bias), no (high risk of bias), and unclear (unknown degree of bias) [Figure 1].

Figure 1.

The risk of bias graph showing the authors’ judgments about each risk of bias item presented as percentages across all included studies

Study selection and data extraction

The data comprising the name of the first author, year of publication, type of study design (interventional, prospective cohort, retrospective, cross-sectional), country, number of samples, gender proportion, average age, blood factors related to the prognosis of cardiovascular events (e.g., troponin, D-dimer) and COVID-19, study duration, follow-up period, CC (such as myocardial damage, acute left ventricular dysfunction, heart failure, arrhythmia, coronary aneurysm, intracardiac thrombosis, and pericardial effusion), the duration of infection with COVID-19, the outcome of the child (complete recovery, recovery with complications, and death), and the severity of the disease (severe, mild, and moderate) were extracted. Data extraction from the selected articles was performed by two authors independently. In case of differences in information recordings, they were discussed and the best information extracted from each study was approved following a final decision.

RESULTS

Twelve studies were included in this review with the selection process shown in Figure 2.

Figure 2.

Flow diagram of our review process (PRISMA)

The characteristics and demographic features of the studies on CI in COVID-19-infected children are summarized in Table 1.

Table 1.

Summary of the data about children and cardiovascular involvement

Author	Study type	Country	Number of patients	Age	Sex	Cardiac enzymes	Cardiovascular involvement	ECG finding	Echo finding	Treatment	Outcome
Sun et al., 2020	Retrospective study	China	8	2 m–15y	6M/2F	Mean D dimer: 8.91 mg/L FEU	LVD (n=1, male)	-	-	Oxygen therapy Antibiotic therapy Antiviral therapy Corticosteroid therapy Anti-antibody therapy Other	Discharged (n=5) Remained in ICU (n=3)
Xia et al., 2020	Retrospective study	China	20	1 d–14 y 7 m	13M/7F	CK‐MB: ≤25 U/L (n=15) >25 U/L (n=5)	-	SVAs (n=3) VA (n=1) Heart block (n=2)	-	-	Discharged (n=18) Under hospitalization (n=2)
Su et al., 2020	Retrospective study	China	9	11 m- 9 y	3M/6F	Mean D dimer: 0.27 mg/L FEU Mean CK-MB: 37.22 U/L Mean BNP: 53.8 pg/mL	MI (n=6)	-	-	Antiviral therapy	Discharged (n=2) Discharged with symptom (n=7)
Dong et al., 2020	Retrospective study	China	2143	7 y [2-13]*	1213 M/930 F	-	MI (n=13)	-	-	-	Under hospitalization (n=2143)
Cui et al., 2020	Case report	China	1	55 d	1 F	D-dimer: 0.54 μg/mL CK‐MB: 46 U/L IgM: 0.66 g/L	MI	-	-	Antibiotic therapy Other	Discharged (n1)
Giacomet et al., 2020	Case report	China	1	2 m	-	TnT T: Positive	MI	Arrhythmia	RWMP (n=1)	Antibiotic therapy Anti-antibody therapy Anti-antibody	Discharged (n=1)
Samuel et al., 2020	Retrospective study	New York	5	12-16 y	-	-	-	VA (n=4) SVAs (n=5)	CDs (n=1) LVD (n=1) LVD (n=1)	Antibiotic therapy	Discharged (n=5)
Joshi et al., 2020	Case series	New York	3	6, 13 y	2 M/1 F	Mean D-dimer: 1770 ng/mL hsTnT: 475, 116, 43 ng/L Mean procalcitonin: 13.95 ng/mL	-	Tachycardia	LVD VHD	Anti-inflammatory Anti-antibody therapy Other	Discharged (n=3)
Bigdelian et al., 2021	Case series	Iran	3	7,8, 11 y	3F	Mean D-dimer: 1006.67 ng/mL Blood culture: negative	LVD (n=3)	Tachycardia (n=3)	LVD (n=3) VHD (n=1)	Anti-antibody therapy Corticosteroid therapy Antibiotic therapy, Antiviral therapy Surgery	Discharged (n=3)
Heching et al., 2022	Retrospective study	USA	82	1-18 y	51 M/31 F	-	-	RA** (n=17)	-	Oxygen therapy Antiviral therapy Antibiotic therapy	Unknown
Powell et al., 2022	Retrospective study	USA	1479*	5-18 y	763 M/718 F	Mean TnT: 2.0 ng/L	-	SVAs (n=203) VA (n=4) Heart block (n=9) RA (n=5)	VHD (n=2) CDs (n=3) LVD (n=2)	Anti-antibody therapy Other	Unknown
Malakan Rad et al., 2022	Case report	Iran	1	3 y	F	troponin I: Normal	LVD and decrease LVEF	RA	Severe decrease in LVEF, mild to moderate MR	Treatment for heart failure	Transfer to the pediatric cardiac center

CK-MB=creatine kinase MB, hsTnT=high-sensitivity troponin T. *: In Powell et al., study, two children with congenital heart disease (including patent foramen ovale (PFO) and patent ductus arteriosus (PDA) were excluded from the sample. **: Repolarization abnormality included borderline significant (included isolated mild PR prolongation or mild repolarization abnormalities) (n = 10), Significant (consisting of more significant repolarization abnormalities) (n = 7). Cardiovascular involvement included[1] LV dysfunction (LVD): Heart failure, Cardiomegaly, Silent myocarditis with progression to dilated cardiomyopathy,[2] Myocardial injury (MI). ECG findings included[1] Supraventricular arrhythmias (SVAs): Sinus tachycardia, atrial tachycardia, PACs,[2] Ventricular arrhythmia (VA): Monomorphic VT, Premature ventricular contractions (PVC),[3] Heart block: prolonged PR interval, and incomplete right bundle branch block (RBBB),[4] repolarization abnormality (RA): T wave inversion in left precordial leads, Q waves in inferior/lateral leads. Echocardiography findings included[1] Regional wall motion abnormality (RWMP): Hypokinesia of the inferior left ventricular wall and the inferior interventricular septum,[2] Valvular heart disease (VHD): Mitral regurgitation, Bicuspid aortic valve,[3] Left ventricle dysfunction (LVD): Mild left ventricle trabeculations, low LVEF,[4] Coronary artery dilations (CDs): Mild right coronary artery dilation, LV dilation. Treatment: Oxygen therapy (oxygen therapy or mechanical ventilation), antibiotic therapy, antiviral therapy, anti-antibody therapy (such as IVIG), corticosteroid therapy, anti-inflammatory, other (traditional Chinese medicine, kidney replacement therapy, milrinone, dobutamine, dopamine, inhaled interferon α-1b, potassium clavulanate)

In the study of Sun et al. in China on 8 children aged 2 months to 15 years with COVID-19, only one boy had heart failure and was admitted to the intensive care unit (ICU).[27] In Xia et al.'s study on 20 children under 14 years of age with COVID-19, it was shown that supraventricular arrhythmias (including sinus tachycardia, atrial tachycardia, premature atrial contractions [PACs]) were the most common finding in patients’ ECGs; in contrast, heart block (including prolonged PR interval, and incomplete right bundle branch block [RBBB]) were also among the other findings of this study.[28]

In the report of Su et al. on 9 children aged 11 months to 9 years, 6 cases suffered from myocardial injury (MI), of which 7 cases were discharged with symptoms.[29] Dong et al. in a large study on 2,143 children, of which 56.6% were boys and 13 cases had MI.[30] Cui et al. also reported a case of a 55-day-old girl in their case report, who had MI, but she was discharged from the hospital with good conditions.[31]

In the case report of Giacomet et al., a 2-year-old child suffered from myocarditis, and echocardiography findings were regional wall motion abnormality (RWMP).[32] In Samuel et al.'s study on 5 children aged 12-16 years with COVID-19, it was shown that arrhythmias were the most common finding in patients’ ECG findings; coronary artery dilations and left ventricle dysfunction (LVD) were also among the echocardiography findings of this study.[33]

In Joshi et al.'s study, 3 children (2 boys and 1 girl) with COVID-19 were examined. According to the ECG and ECHO findings, valvular heart disease (VHD), LVD, and tachycardia were reported for them respectively.[34] Bigdelian et al. reported three cases of COVID-19 children with acute intracardiac thrombosis treated with cardiac surgery. Left ventricular ejection fraction (LVEF) in three cases was reported as 64%, 69%, and 68%. Tricuspid regurgitation (TR) and trivial pulmonary insufficiency (PI) were reported in all children. In one case, mitral regurgitation (MR) and a large mobile mass in the left atrium (LA) with attachment to the posterior leaflet of the mitral valve were reported. Their clinical conditions improved after surgery, and the postoperative echocardiography results showed a normal heart function and they were discharged with good health condition.[35]

Heching et al.'s study on 82 children aged 1–18 years showed that 10 children had ECG of borderline significance, which included isolated mild PR prolongation or mild repolarization abnormalities. Seven children had concerning ECG findings consisting of more significant repolarization abnormalities.[36] In a large study by Powell et al. on 1,479 children aged 5–18 years (2 children with congenital heart disease were excluded) echocardiographic findings including bicuspid aortic valve, moderately dilated ascending aorta/aortic root, and mild right coronary artery dilation. Also, ECG findings included supraventricular arrhythmias (SVAs) (such as sinus, ectopic atrial, left atrial enlargement, right atrial enlargement, and premature atrial contractions), ventricular arrhythmia (VA) (such as PVC and ventricular preexcitation), heart block (such as right bundle branch block and prolonged QT interval) and repolarization abnormality (RA) (such as deep Q waves in inferior/lateral leads, non-specific ST/T wave changes).[37] In a case report by Malakan et al., a 3-year-old girl had CI, which was reported as left ventricular dysfunction. Also, there was evidence of repolarization abnormality in the ECG findings. This patient was referred to the pediatrics’ heart center for additional treatment.[38]

DISCUSSION

This review summarizes the current evidence on CI in COVID-19-infected children. Although respiratory disease is the predominant clinical manifestation of COVID-19, cardiovascular disorders are being introduced as one of the most important complications of SARS-CoV-2 infection in children.

Information about COVID-19 in children is still very sparse, and so far not many severe cases have been reported in children. Despite this, apparently, they are less susceptible to severe symptoms of COVID-19, but cardiac involvement has occurred in a number of them, which indicates that the heart can also be a possible target of the disease in this age range.

The SARS-CoV-2 virus is a large, enveloped, single-stranded RNA virus that binds to the ACE 2 receptor on the surface of the host cell with the viral S (spike) protein. As the viral S protein binds to the ACE2 receptor, type 2 transmembrane serine protease in the host cell increases the viral uptake by cleaving ACE2 and SARS-CoV-2 protein activation and then mediates the coronavirus entrance into host type II alveolar epithelial cells.[39,40] Three mechanisms have been proposed for CI in SARS-CoV-2 infection: direct viral invasion of cardiomyocytes, high expression of ACE2 receptors resulting in direct cell damage; cardiac injury induced by acute immune inflammatory response and cytokine storm; and severe hypoxia, causing ischemic MI[40,41,42,43,44]. Because ACE2 receptors are increased during older ages, lower levels of ACE2 may partly account for less severe acute SARS-CoV-2 infections in children. Other studies have shown that children have less ACE2 receptors in the nose, which reduces the ability of SARS-CoV-2 to bind and reduces the severity of the disease.[45,46,47]

Cardiovascular manifestations due to acute infection of COVID-19 are not common in children; however, some case reports and small series have reported cardiac shock, myocarditis, pericarditis, and arrhythmia.[48,49,50,51] Arrhythmias including ventricular tachycardia and atrial tachycardia, and also first-degree atrioventricular block.[28] Although they are usually not persistent and resolve spontaneously without treatment, in some cases, prophylactic antiarrhythmic drugs have been prescribed, and death from recurrent ventricular tachycardia has been reported in an adolescent with hypertrophic cardiomyopathy.[52] Increased troponin, electrocardiographic abnormalities, including ST segment changes, and delayed gadolinium enhancement have been observed on cardiac magnetic resonance imaging (CMRI) in subjects with myocardial involvement.[31,53,54] Although death is rare in children with severe myocardial involvement, both sudden cardiac death and death have occurred after intensive medical and supportive care such as extracorporeal membrane oxygenation (ECMO).[55,56]

SARS-CoV-2 continuously infects patients worldwide and its variants are circulating around the world. There is much to learn about the disease pathology; however, continued clinical research on the treatment of COVID-19 and the management of pediatric and its long-term cardiovascular manifestations in children is needed. It is worth mentioning that severe acute cardiovascular events in the form of new arrhythmia, pulmonary hypertension (PH), heart failure, and even fulminant myocarditis have occurred in a not insignificant number of affected children who were previously healthy. They often showed cardiac shock at a rate of 53%, ECG changes at 27%, myocardial dysfunction at 52%, and coronary artery dilatation at 15%. Pediatric intensive care unit (PICU) admission was required for 75% and inotropic support for 57%, with a rare requirement of 4% for extracorporeal membrane oxygenation. Nearly all children made a full recovery within a few days although a rare mortality rate of 2% has been reported. These observations indicate that no child is immune to cardiovascular events during SARS-CoV-2 infection, although these cases are rare.[57]

Since the beginning of the epidemic, several cases of CI similar to adults such as myocarditis, heart failure, cardiac shock, pericarditis, cardiac arrhythmia, and PH have been reported in children. Although rare, these cases are usually reported as severe or critical patients, which also points to the association of cardiac involvement in previously healthy children who contract COVID-19. A series of cases of 2,135 children infected with COVID-19 across the country have been reported to the Centers for Disease Control and Prevention in China. CI was observed in 13 patients with myocardial damage or heart failure, and no deaths were reported.[30]

Thirty-six children with active polymerase chain reaction (PCR)-positive SARS-CoV-2 infection were included in Samuel et al.'s study, none of them had pre-existing heart disease, and 6 of them had significant arrhythmias, including non-sustained ventricular tachycardia in 5 cases and tachyarrhythmias. Stable atrial cardiomyopathy was observed in 1 case. All episodes were self-resolving and 3 of them started with prophylactic antiarrhythmic therapy. An abnormal echocardiogram with mild left ventricular dilatation/dysfunction was observed in 4 cases, which improved at discharge.[33]

Xia et al. reported the chest computed tomography (CT), clinical and laboratory features in 20 inpatients pediatric COVID-19 confirmed by pharyngeal swab COVID-19 nucleic acid test. They observed self-limited ECG alterations in four cases during admission including atrial and ventricular premature beats, sinus tachycardia, first-degree atrioventricular block, and atrial arrhythmia.[28]

According to a few published data, SARS-CoV-2 can be a potential new cause of fulminant myocarditis and should be considered in COVID-19 patients with acute onset of chest pain, cardiac arrhythmias, hemodynamic instability, and ST segment changes.[58,59] Also, LV dilatation, LV hyposystole based on echocardiography, and significant increases in cardiac troponin and proBNP levels can occur, and myocarditis, although a rare event in these patients, appears clinically early and can lead to sudden cardiac death. However, not many studies are available on myocardial injuries in these COVID-19 patients, and it is necessary to clarify its impact on clinical prognosis in them.

Little is known about the occurrence of arrhythmia in children with COVID-19. In two small studies, it was shown that the rate of cardiac arrhythmia can be 16–20% in children hospitalized with COVID-19.[59,60] Preliminary data from observational Chinese studies suggest that unlike adult patients that their myocardial involvement is occasionally associated with life-threatening arrhythmias, in children, rhythm problems, such as supraventricular tachycardia, first-degree atrioventricular block, bundle branch block incomplete right premature, atrial and ventricular complexes are observed less often.[28] Based on these few data, arrhythmia represents a clinical manifestation of COVID-19, which is not rare and can complicate the clinical course of the disease in hospitalized patients and worsen their prognosis. Therefore, careful electrocardiographic monitoring should be performed in COVID-19 patients for the early detection of an arrhythmia attack that does not match the disease state and may be a sign of worsening disease.

It seems that VA is directly related to myocardial damage caused by COVID-19. Accordingly, a higher incidence of VA was reported to be associated in adult patients with increased troponin-T levels.[61,62] Notably, abnormal echocardiograms with mild left ventricular dilatation/distortion were observed in four of five cases reported by Samuel et al.[33] Ventricular fibrillation has also been observed in some cases of fulminant myocarditis and sudden cardiac death in children.[57,59] Therefore, direct myocardial damage seems to be a determinant factor for arrhythmias in children. In the acute phase of severe COVID-19, hypoxemia, and electrolyte imbalance are not rare and can also cause cardiac arrhythmia.[63] Lack of accurate identification and timely management of CC can lead to increased complications and mortality of these patients. So, it is recommended to screen children with COVID-19 who are sick enough to require hospitalization for cardiovascular issues. Also, careful cardiovascular monitoring during hospitalization should be ensured to avoid misdiagnosis of these life-threatening factors. The pediatric cardiology team should be involved in the management of any child with pre-existing heart disease and the screening of any healthy child with a pre-existing abnormality. In the absence of sufficient evidence, management of cardiac complications after detection should be according to the current guidelines, local protocols, and physician experience unique to each disease.[64]

So far, there is not much information about the role of COVID-19 in CI in children. Based on this study, CI appears to be associated with SARS-CoV-2 infection in children. In previously healthy children, COVID-19 can also cause fulminant myocarditis, VA, and PH. Data have shown that if the cardiovascular system is compromised in children during SARS-CoV-2 infection, the prognosis is worse, and the greatest part of CC shows complete recovery with timely support. Because early identification and treatment of these factors is critical, cardiac workup and close cardiovascular monitoring of severe SARS-CoV-2-infected children are strongly recommended.

The strength of this study was including studies on children without comorbidities or underlying disease, but it can be considered for the next investigation to work on children with congenital and associated diseases based on the type of complications. It is also suggested to perform more systematic or meta-analyses on the outcomes of maternal COVID-19 in infants and children regarding the short- and long-term follow-ups.

CONCLUSION

It is worthy to note that no death has been reported in our study, which can be due to including the studies on healthy children with COVID-19. According to the results of this study and based on the ECG findings, supraventricular arrhythmias and ventricular arrhythmia were the more prevalent outcomes, and on the basis of ECHO findings, LVD had the highest rate. Also, in CI, MI has been the most frequent.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.