Post–COVID-associated cardiovascular sequelae have been investigated in detail for adults,1–3 whereas data on children remain scarce. The prevalence of post-COVID symptoms in adults and children continues to be a topic of debate, with prevalence statistics ranging from 4% to 66%.4 To date, most pediatric COVID-19 studies focused on the acute condition of hospitalized patients,5,6 rather than long-term outcomes of nonhospitalized patients. For example, in patients with pediatric inflammatory multisystem syndrome, who received cardiac magnetic resonance (CMR) assessment with follow-up, a transient cardiac inflammatory response rather than persistent myocardial injury could be observed.7 Although children with post-COVID syndrome (PCS) presumably only represent a minor fraction of the COVID infected, their incomplete recovery has detrimental consequences on the quality of life for both the patients and their families.8

Post-COVID syndrome has been defined in the UK NICE (National Institute for Health and Care Excellence) guidelines as the persistence of symptoms beyond 12 weeks after COVID infection for which no alternate diagnosis is likely.9 Typical symptoms include fatigue, dyspnea, lack of concentration, palpitations, rashes, headache, and chest pain.2 The majority of symptoms suggest cardiopulmonary involvement. In a cohort of 346 adults with persistent post-COVID symptoms associations with diffuse myocardial edema, late gadolinium enhancement (LGE) and cardiac strain impairment were reported.1 Interestingly, high levels of cardiac and inflammatory biomarkers, such as troponin and C-reactive protein (CRP), rarely correlated with persistent symptoms.1 Another recently published study reported no major differences regarding tissue characterization, strain, and myocardial structure using CMR.10 To our knowledge, the extent to which the inflammatory sequelae of PCS affect the myocardium in children has not been studied.

The diagnostic power of multiparametric CMR assessment, particularly regarding cardiac strain, tissue characterization, and contrast-enhanced imaging, has been recently described.11–13 The present study focuses comprehensively on the function of CMR for diagnostic discrimination of post–COVID-associated abnormalities in myocardial structure, function, and tissue characterization in children. The main hypothesis of the present study is that CMR imaging parameters among children with PCS differ from those in age- and sex-matched healthy controls. The fundamental objective is to manifest cardiovascular sequelae using multiparametric CMR assessment that aids in the diagnostic consolidation of PCS.

MATERIALS AND METHODS Study Population

This is a prospective, intraindividual, cross-sectional, observational study at a single center. Patients were derived from the LoCoKi (“Long COVID Kids Niedersachsen”) study cohort. The LoCoKi study is a prospective observational study on children and adolescents with laboratory-confirmed COVID-19 infection and persistent symptoms attributed to PCS according to international guidelines.14 Recruitment started in April 2022; this analysis includes patients recruited until October 2022. Post-COVID eligibility screening selects for inclusion criteria. Inclusion criteria were as follows: children of maximum 17 years of age, with at least 12 weeks past their positive SARS-CoV-2 test (PCR or serology), and presenting with typical post-COVID lingering symptoms after COVID infection. Pediatric specialists conducted physical assessment and working diagnosis. Exclusion criteria were preexisting cardiovascular, pulmonary, endocrinological, rheumatological, or oncological diseases; contraindication for magnetic resonance imaging (MRI) examinations; or unwillingness to participate. Contrast-enhanced imaging was conducted only in children with PCS if no contraindications were present. The enrollment process is illustrated in the flowchart (Fig. 1).

FIGURE 1:

Study flowchart of participant enrollment.

Healthy Control Subjects

Age- and sex-matched healthy children with maximum 17 years of age served as controls. A written informed consent was obtained from all participants and their legal guardians. The timeframe of enrollment encompassed February 2022–January 2023. The exclusion criteria for healthy volunteers were cardiopulmonary, metabolic, and endocrinological diseases along with contraindications for CMR. If CMR imaging demonstrated myocardial abnormalities, aortic ectasia, pulmonary trunk dilation, valvular heart disease, ischemic heart disease, signs of cardiomyopathy, or pulmonary abnormalities, this volunteer would be excluded. Control subjects were age- and sex-matched to children with PCS (Fig. 1). Contrast administration in the control cohort marked an ethical and moral conflict by our local ethics committee. This was underscored by the absence of a clinical indication for contrast administration in healthy controls. All examinations were done in accordance with the 1964 declaration of Helsinki, and the local ethics committee (institutional review board number: 10207_BO_K_2022) approved the study.

Clinical Parameters

Baseline clinical data of patients with PCS were recorded in the course of their physical assessment by a pediatric physician, which included age, weight, height, body mass index (BMI), and heart rate. In addition, the children provided certified evidence of SARS-CoV-2 infection from which the time since infection was calculated. Blood samples included cTroponin, NTproBNP (N-terminal prohormone of brain natriuretic peptide), CRP, d-dimer, interleukin-6, serum ferritin, number of leukocytes, lymphocytes, thrombocytes, and hematocrit.

Cardiac MRI

Cardiac magnetic resonance examinations were performed in accordance to a standard diagnostic protocol for myocarditis. All subjects underwent CMR at our institution using a 3.0 T MRI system (Magnetom Vida, Software Version VE11; Siemens Healthineers). Vector electrocardiogram-triggered cardiac cine acquisitions were performed on all patients.

Details of the MR sequences used are available in the electronic Supplementary Material (Table S1, https://links.lww.com/RLI/A883). An axially acquired stack covering the whole heart, a short-axis stack covering the entire left and right ventricles, as well as 2-, 3-, 4-chamber longitudinal axis views were acquired with retrospectively gated cine steady-state free-precession acquisitions (True FISP) for the assessment of biventricular volumes and function. Native T1 and T2 maps were acquired in the short axis at basal and midventricular level, using a MOLLI (modified look-locker inversion recovery) sequence and a T2 gradient echo FLASH (fast low-angle shot) sequence, respectively. As recommended by Messroghli et al,15 we used a balanced steady-state free-precession sequence combined with a reduced flip angle of 35 degrees to minimize the influence of the heart rate on T1. The decreased flip angle reduces the disturbance of signal recovery by the readouts and therefore the influence of the heart rate on T1. Postcontrast T1 maps were acquired 10 minutes after intravenous application of 0.1 mmol kg−1 gadobutrol (Gadovist; Bayer Healthcare) using phase-sensitive inversion recovery sequencing. In addition, the extracellular volume (ECV) was calculated as previously described by Bauner et al.16 Unfortunately, 4 children with PCS could not be assessed for LGE pattern and ECV, as they did not receive MR contrast medium agent due to the abortion of MRI examination.

Cardiac MRI Postprocessing

Postprocessing was conducted using the CVI42 software package (Release 5.12.1; Circle Cardiovascular Imaging Inc). The short-axis, 4-chamber, and vertical long-axis cine steady-state free-precession acquisitions were processed for functional and strain assessment of the right and left ventricle, as previously described.17 At end-diastole and end-systole, contours of left and right ventricular endocardium and epicardium were delineated semiautomatically in short axis, 4-chamber axis, and vertical longitudinal axis. All volumetric indices were normalized to body surface area. Aside from global strain quantification, strain values were assessed on the basis of the American Heart Association segmentation of the left ventricle for the possibility of regional differences at basal, midventricular, and apical level.18 Myocardial T1 and T2 relaxation times were measured at basal and midventricular level for the septal, inferior, and lateral left ventricular wall via manual contouring (Fig. 2) as recently described.19 Moreover, local established pediatric norms were further included for comparison of T1 and T2 relaxation times in children with PCS, along with their frequency of abnormalities. Abnormalities were determined based on relaxation times in children with PCS that exceeded the upper boundaries of the established norms. In concordance with the publication of Blondiaux et al,19 the apical short axis slice was not analyzed due to its vulnerability of artifacts.

FIGURE 2:

Manual septal (pink), lateral (turquoise), and inferior (yellow) contouring represent the region of interest for the basal and midventricular left ventricle in short axis plane.

The updated Lake Louise Criteria (LLC)20 were applied throughout this study as a standardized approach to assess myocardial inflammation. The assessment incorporated T2 relaxation times, T1 relaxation times, ECV quantification, and LGE imaging. A cutoff value for reference was derived from the upper boundary from locally established norms to determine abnormalities in relaxation times.

Statistics

Statistical analysis was performed using SPSS (version 27.0.0.0; IBM Deutschland GmbH). Continuous variables are presented as mean ± standard deviation. Baseline parameters and cardiac parameters of the children with PCS and their matched healthy volunteers were compared using a Student t test for parametric distribution or Mann-Whitney U test for nonparametric distribution. The Shapiro-Wilk test was used to differentiate between parametric and nonparametric distribution. P values <0.05 were considered statistically significant. Interobserver and intraobserver variability were tested using intraclass correlation analyses (2-way mixed model, absolute agreement) and coefficients of variation.21 Two experienced radiologists quantified septal T2 relaxation time, septal T1 relaxation time, global radial, global longitudinal, and global circumferential strains at basal level on 20 randomized healthy subjects to obtain intraobserver and interobserver variability. All intraobserver and interobserver variability resulted in good intraclass correlation coefficients (>0.8) and low coefficients of variation. Intraobserver and interobserver variability data are summarized in Table S2, https://links.lww.com/RLI/A883.

RESULTS Clinical Parameters

Clinical and CMR parameters are presented in Table 1. Twenty-nine age- and sex-matched children with PCS and healthy controls were enrolled in this study. The mean age was 14.0 ± 2.8 years for children with PCS and 14.0 ± 2.7 years for controls (see Table 1). Age, weight, height, and BMI were comparable for both groups (P > 0.05). The mean time between certified positive COVID test and post-COVID patient presentation at the post-COVID children outpatient department was 36.4 ± 24.9 weeks. A SARS-CoV-2 infection for children with PCS was certified with PCR for 26 cases, with professional antigen tests for 2 cases and a self-performed antigen test for only 1 case. None of the children experienced COVID-associated hospitalization. Common persistent symptoms entailed fatigue, concentration disorders, dyspnea, and dizziness. The heart rate was significantly elevated among PCS patients in comparison to controls (83.7 ± 18.1 vs 75.2 ± 11.2 beats per minute; P = 0.019). A significantly elevated right ventricular indexed end-diastolic and end-systolic volume was observed in children with PCS compared with controls (RVEDVi: 95.2 ± 19.2 mlm−2 vs 82.0 ± 21.5 mlm−2, P = 0.018; RVESVi: 40.3 ± 7.9 mlm−2 vs 34.8 ± 6.2 mlm−2, P = 0.005). Extracellular volume was found marginally elevated (31.1% ± 3.7%) for children with PCS compared with literature sources reporting 28% as a cutoff value in children and young adults.22–24 A patchy, transmural, nonischemic LGE of the midventricular septal wall was only found in 1 child with PCS, accompanied by biventricular dilatation. Although there was no corresponding visual edema, midventricular septal T1 and T2 relaxation times were found comparatively elevated (T1: 1251 ± 114 milliseconds; T2: 42.7 ± 1.02 milliseconds) in this patient.

TABLE 1 - Clinical Parameters of Children With PCS and Controls Parameter Children With PCS Controls P Tested by Student t Test† or Mann-Whitney U Test‡ No. subjects 29 29 Male, % 15 (52%) 15 (52%) Age, y 14.0 ± 2.8 14.0 ± 2.7 0.927‡ Weight, kg 55.3 ± 17.8 56.9 ± 19.2 0.373‡ Height, cm 164.6 ± 14.0 163.5 ± 15.0 0.394† BSA, m2 1.6 ± 0.3 1.6 ± 0.3 0.301† BMI, kg/m2 20.1 ± 5.4 20.7 ± 4.3 0.298‡ Heart rate, bpm 83.7 ± 18.1 75.2 ± 11.2 0.019† Mean time post-COVID infection, wk 36.4 ± 24.9 (range, 12.1–113.1) — Status post COVID infection, % 29 (100%) 27 (93%) Positive vaccination status, % 24 (83%) 27 (93%) Symptoms  Fatigue, % 29 (100%) —  Concentration disorders, % 16 (55%) —  Dyspnea, % 15 (52%) —  Dizziness, % 9 (31%) —  Muscle ache, % 8 (28%) —  Chest pain, % 7 (24%) —  Abdominal pain, % 6 (21%) —  Headache, % 3 (10%) —  Hyposomnia, % 1 (3%) — Cardiac function and vitality  LVEF, % 63.1 ± 4.3 64.0 ± 2.8 0.165†  LVEDVi, mlm−2 86.1 ± 14.4 78.9 ± 16.3 0.245‡  LVESVi, mlm−2 31.6 ± 5.6 29.7 ± 6.2 0.125†  LVmyomass, gm−2 52.4 ± 10.0 49.0 ± 11.1 0.120†  RVEF, % 57.4 ± 4.8 59.0 ± 3.6 0.091‡  RVEDVi, mlm−2 95.2 ± 19.2 82.0 ± 21.5 0.018†  RVESVi, mlm−2 40.3 ± 7.9 34.8 ± 6.2 0.005†  RVmyomass, gm−2 11.1 ± 2.9 10.9 ± 4.2 0.272†  Dyskinesia 1 (3% of 29) 0 —  Pericardial effusion 1 (3% of 29) 0 —  LGE (nonischemic) 1 (4% of 25)* — —  ECV, % 31.1 ± 3.7* —  Fulfillment of LLC, % 20 (69%)

BSA, body surface area; BMI, body mass index; bpm, beats per minute; LVEF, left ventricular ejection fraction; LVEDVi, indexed left ventricular end-diastolic volume; LVESVi, indexed left ventricular end-systolic volume; LVmyomass, left ventricular myocardial mass; RVEF, right ventricular ejection fraction; RVEDVi, indexed right ventricular end-diastolic volume; RVESVi, indexed right ventricular end-systolic volume; RVmyomass, right ventricular myocardial mass; LGE, late gadolinium enhancement; ECV, extracellular volume; LLC, Lake Louise Criteria; PCS, post-COVID syndrome.

*n = 25 patients, as in 4 children with PCS, contrast medium was not applied.

†Student t test.

‡Mann-Whitney U test.

Laboratory Biomarkers

Laboratory biomarkers are summarized in Table 2. All cardiac and inflammatory biomarkers, per example cTroponin (4.2 ± 1.6 ngl−1), interleukin-6 (0.8 ± 1.6 ngl−1), CRP (0.2 ± 3.5 mgl−1), and blood coagulation markers, per example d-dimer (0.2 ± 0.3) and number of thrombocytes (265.6 ± 55.2), were found within reference range. Although the average values fell within the reference range, 10% of children with PCS exhibited abnormalities in d-dimer and lymphocyte levels, whereas 28% showed abnormalities in NTproBNP levels.

TABLE 2 - Laboratory Biomarkers of Children With PCS Laboratory Biomarkers Children With PCS Reference Values Frequency of Abnormalities,* % Range cTroponin, ngl−1 4.2 ± 1.6 <14 ngl−1 0 1.0–8.0 NTproBNP, ngl−1 17.9 ± 27.9 <50 ngl−1 8 (28%) 1.0–78.0 CRP, mgl−1 0.2 ± 3.5 <5 mgl−1 0 0.1–1.3 d-dimer, mgl−1 0.2 ± 0.3 0–0.5 mgl−1 3 (10%) 0.01–0.93 Leukocytes, 1000/μL 5.7 ± 1.6 4.2–10.8, 1000/μL 0 0.2–9.5 Lymphocytes, % 32.2 ± 12.1 20%–44% 3 (10%) 8.9–57.7 Interleukin-6, ngl−1 0.8 ± 1.6 <7 ngl−1 0 0.1–5.0 Serum ferritin, μgl−1 47.1 ± 21.1 27–365 μgl−1 0 9.0–97.0 Thrombocytes, 1000/μL 265.6 ± 55.2 160–385, 1000/μL 0 175.0–377.0

*Abnormalities were determined based on the number of cases for which the biomarker exceeded the reference range.

PCS, post-COVID syndrome; NTproBNP, N-terminal prohormone of brain natriuretic peptide; CRP, C-reactive protein.

CMR Tissue Characterization

The T1 and T2 relaxation times (Table 3 and Fig. 3) were significantly higher in children with PCS compared with healthy controls at the basal and midventricular levels of the left ventricle. For example, at the basal septal level, T1 was 1217.4 ± 79.7 milliseconds in children with PCS versus 1164.1 ± 35.9 milliseconds in healthy controls (P = 0.001), and T2 was 42.0 ± 2.2 milliseconds in children with PCS versus 39.0 ± 3.2 milliseconds in healthy controls (P < 0.001). In children with PCS, 48% to 76% of cases had T1 values exceeding the upper limit of the established norms, whereas T2 values ranged from 7% to 66% above the norm. Overall, 20 children with PCS met the updated LLC, indicating the presence of myocardial inflammation. Notably, the additional criteria involving ECV and LGE did not change the count of LLC-positive cases. Thus, quantified T1 and T2 relaxation times formed the core criteria for LLC classification.

TABLE 3 - T1 and T2 Mapping of the Basal and Midventricular Left Ventricle for Children With PCS and Controls Parameter Children With PCS Controls P Tested by Student t Test† or Mann-Whitney U Test‡ Upper Boundary of the Established Norm Frequency of Abnormalities,* % T1 mapping  Basal   Septal, ms 1217.4 ± 79.7 1164.1 ± 35.9 0.001† 1190.9 22 (76%)   Lateral, ms 1194.0 ± 67.0 1137.4 ± 49.1 <0.001† 1164.6 22 (76%)   Inferior, ms 1210.8 ± 151.7 1140.7 ± 54.4 0.011‡ 1198.9 17 (59%)  Midventricular   Septal, ms 1216.7 ± 94.4 1164.9 ± 37.6 0.004† 1193.6 17 (59%)   Lateral, ms 1205.5 ± 92.1 1145.8 ± 72.7 0.005† 1180.2 17 (59%)   Inferior, ms 1189.5 ± 67.1 1142.6 ± 38.3 0.001‡ 1192.6 14 (48%) T2 mapping  Basal   Septal, ms 42.0 ± 2.2 39.0 ± 3.2 <0.001† 42.7 9 (31%)   Lateral, ms 41.1 ± 4.0 37.4 ± 2.9 <0.001† 41.4 11 (38%)   Inferior, ms 40.5 ± 3.2 36.8 ± 2.5 <0.001† 39.7 19 (66%)  Midventricular   Septal, ms 42.3 ± 2.9 39.8 ± 3.9 0.005† 43.5 6 (21%)   Lateral, ms 41.3 ± 3.5 38.8 ± 3.6 0.013† 43.8 5 (17%)   Inferior, ms 40.0 ± 2.9 38.1 ± 3.3 0.008† 43.2 2 (7%)

*Abnormalities were determined based on relaxation times that exceeded the upper boundaries of the established norms.

†Student t test.

‡Mann-Whitney U test.

PCS, post-COVID syndrome.

FIGURE 3:

Regional T1 and T2 mapping values of post-COVID patients and healthy volunteers for the left ventricular myocardium. *Statistically significant difference (P < 0.05).

Strain assessment revealed no differences (P > 0.05) between children with PCS and healthy controls, neither at a global level for both ventricles (Table 4) nor in the American Heart Association segmented left ventricle regarding circumferential, radial, and longitudinal strain (Tables S3–S5, https://links.lww.com/RLI/A883). The larger standard deviations in segment-based strain quantification, compared with global-based strain quantification, align with previous findings reported by Andre et al.25 For this reason, Andre et al25 recommended evaluating global strain values due to their greater robustness in distinguishing from pathological values, lower evaluation effort, and higher reproducibility compared with segment-based strains.

TABLE 4 - Global Left Ventricular Strains of the Left and Right Ventricle for Children With PCS and Controls Parameter Children With PCS Controls P Tested by Student t Test* or Mann-Whitney U Test† Global strain of left ventricle  Circumferential (SAX), % −13.5 ± 3.5 −15.1 ± 4.1 0.055*  Radial (SAX), % 24.0 ± 7.7 28.6 ± 9.7 0.053*  Longitudinal (LAX), % −22.9 ± 6.1 −22.7 ± 3.1 0.434* Global strain of right ventricle  Circumferential (SAX), % −19.5 ± 1.6 −19.6 ± 1.6 0.912†  Radial (SAX), % 33.7 ± 7.2 34.8 ± 5.0 0.257*  Longitudinal (LAX), % −17.2 ± 2.4 −17.4 ± 2.6 0.384†

*Student t test.

†Mann-Whitney U test.

PCS, post-COVID syndrome; SAX, short axis; LAX, longitudinal axis.

Although global circumferential and radial strain of the left ventricle did not reach statistical significance, the data suggest a tendency of impairment in children with PCS compared with healthy controls (−13.5 ± 3.5 vs −15.1 ± 4.1, P = 0.055 and 24.0 ± 7.7 vs 28.6 ± 9.7, P = 0.053); for details see Table 4.

DISCUSSION

This study provides a comprehensive CMR assessment for myocardial function, tissue characterization, and strain of children experiencing PCS with comparison to age- and sex-matched healthy individuals. The need to investigate postinfection sequelae is underlined by incongruence of the data currently available.1,10 The following novelties were observed in this study:

Right ventricular end-diastolic and end-systolic volumes are significantly increased in children with PCS in comparison to controls. T1 and T2 mapping values are significantly elevated among children with PCS compared with controls. The LLC exhibits diagnostic potential for evaluating myocardial inflammation in children with PCS. Cardiac strains in general provide no significant discriminatory values between children with PCS and controls.

In the present study, an increase in indexed end-diastolic and end-systolic volume of the right ventricle was observed in children with PCS compared with age- and sex-matched healthy controls, whereas left ventricular volumetry was preserved. It can be hypothesized that the observed CMR findings reflect an altered cardiac functional state, which may be related to increased afterload due to pulmonary impairment, as functional MRI of the lungs in patients with persistent symptoms of COVID-19 infection has revealed defects in perfusion and flow-volume loop correlation.26 Subsequent hypoxia has the potential to initiate a vicious cycle, stimulating the transcription of inflammation-related genes and exacerbating endothelial damage via the hypoxia-inducible factor and NF-κB pathway.27 Moreover, hypoxia has been implicated in platelet hyperresponsiveness and aggregation, impairing the pulmonary microcirculation and exacerbating pulmonary dysfunction.28 These alterations in pulmonary function may be partially responsible for the common dyspnea exhibited by children with PCS. Moreover, they may explain the elevated right ventricular end-diastolic and end-systolic volume that may take place due to increased pulmonary artery pressure and subsequent elevated right ventricular afterload. In addition, the elevated heart rate may imply a compensatory mechanism to counteract subclinical diastolic impairment. As the children with PCS have no preexisting heart disease, their cardiac function is likely to remain compensated in the long term. However, the long-term effects of chronic myocardial inflammation in PCS remain unknown.

In the presented study, discriminative differences for T1 and T2 relaxation times between children with PCS and controls could be found. Recently, native T1 and T2 mapping values were described as predictive parameters for symptom persistence at follow-up in adults with post-COVID.1 The present study may contribute to our understanding of the underlying pathophysiological changes that occur for PCS in children. In line with recent observations in adults,1 we found elevated T1 and T2 relaxation times for post-COVID children compared with controls. Considering the frequency of abnormalities in T1 and T2 relaxation times among children with PCS, it seems that T1 mapping holds greater potential as a discriminative tool compared with T2 mapping in clinical practice. Moreover, 69% of children with PCS met LLC criteria. This observation is suggestive of myocardial inflammation as an underlying pathological mechanism in PCS. In addition, this finding underscores the diagnostic potential of the LLC for myocardial inflammation assessment. Although ECV did not alter the number of positive LLC cases, its increase in children with PCS consolidates the presence of myocardial inflammation when considering 28% as the upper normal boundary for children and young adults.22–24 Overall, these findings may indicate increased membrane permeability, resulting in observed extracellular matrix volume expansion due to hyperemia.

Direct tissue injury and its associated fibrotic remodeling seem to be an exception rather than a commonality, consistent with findings in adults.1,10 Only one child with PCS in our cohort presented LGE. Disappearance of edema and LGE persistence are characteristics compatible with literature reportings of chronic myocarditis.29 Although LGE remains a rare finding associated with dilatative cardiomyopathy,30 dilatative cardiomyopathy cannot be ruled out by CMR in the presence of marginal biventricular dilatation for the sole LGE-positive case of the present study. Overall, the diagnostic value of LGE and the impact of the updated LLC20 for chronic myocarditis are subject of ongoing debate.30 Our results cast doubt on the implication of LGE for diagnosing chronic myocarditis in children with PCS. Instead the findings of the present study underscore that quantitative T1 and T2 mappings present valuable diagnostic CMR parameters to LGE, supported by observations made by Aquaro et al.29

In contrast to the acute COVID syndrome, which has been associated with a cytokine storm31 along with elevated interleukin-6 and serum ferritin levels,32 PCS is associated with normal levels of inflammatory cells, inflammatory biomarkers, and cardiac biomarkers, consistent with recent literature.1,33 However, upon discriminating for frequency of abnormalities, a few children with PCS were identified with abnormalities for which 28% constitutes for NTproBNP. To date, similar observations have been made for postacute COVID adult patients, whereby NTproBNP levels were significantly raised in symptomatic versus asymptomatic patients.34 More