The COVID-19 pandemic has had a significant impact on the health of people of all ages worldwide, including children and adolescents. While most children show mild or asymptomatic courses of the disease, there is increasing evidence that they may also be affected by long-term health consequences, particularly with regard to cardiac function. Studies have shown that COVID-19 can affect not only the respiratory system but also the cardiovascular system, which can lead to a variety of cardiovascular complications (1, 2). Post Covid syndrome (PCS) is presently defined by the German Society for Pediatric Medicine (DGKJ) and the National Institute for Health and Care Excellence (NICE) as typical COVID symptoms that last at least 12 weeks after PCR confirmed SARS-CoV-2 infection and can not be explained by other diagnosis (3). Approximately 100 symptoms have now been described related to PCS, all of which can also occur in other diseases, meaning that the diagnosis of PCS remains a diagnosis of exclusion. PCS limits the quality of life of children, adolescents and their parents. In a large pediatric study (4). including children (7–16 years) with PCS, the most common symptoms were loss of smell/taste, fatigue, lack of concentration, respiratory symptoms, dizziness, chest pain and muscle weakness. Also mental health symptoms such as dysthymia seem to be prominent in children with PCS (5). Overall, PCS is a very complex and challenging clinical diagnosis, defined and treated differently in different centers and studies (4, 6). The actual cardiopulmonary risk of children suffering from PCS is still unclear (7). The aim of our study is the accurate cardiac phenotyping, including cardiac function and morphology, in children with PCS by using methods such as cardiac magnetic resonance imaging (CMR) (gold standard for the assessment of cardiac function), echocardiography (Echo) and electrocardiogram (ECG). An age-matched healthy control group is intended to objectively determine possible deviations to the healthy pediatric population. In particular, the detailed investigation of myocardial contractility in PCS patients using strain analyses, determined by CMR and Echo, should provide possible myocardial functional impairments that may indicate long-term inflammatory processes. Identification of an altered cardiac function and morphology may indicate possible pathophysiological mechanisms in the long-term course of Covid-19 disease and should be investigated further. The present work aims to emphasize the need for comprehensive cardiological evaluation and follow-up in children with PCS and to contribute to a better understanding of the long-term cardiovascular consequences of Covid-19 in children and adolescents.

Complete and detailed results as well as the most common symptoms in pediatric PCS are shown in Table 1 (Echo, ECG) and Table 2 (conventional CMR, CMR Strain). Significant differences (p value < 0.05) in CMR parameters are shown in Figure 1. Only 9 of 100 pediatric PCS patients had a slightly elevated NTproBNP between 100 and 200 ng/L, the remaining patients had an NTproBNP <100 ng/L. Inflammation markers (CRP, IL-6, ESR) were not elevated in PCS patients. None of the PCS patients showed a pathologically elevated troponin T value. We saw no significant difference (p value > 0.05) in the conventional echocardiographic parameters between the PCS patients and the control group. In particular, left ventricular ejection fraction (LVEF), right ventricular (RV) dimensions (RVEDD, RVAWd) and tricuspid annular plane systolic excursion (TAPSE) did not differ significantly. RV longitudinal global and free-wall strain derived by Echo showed normal values in both groups. The ECG times as well as basal heart rates did not differ significantly between the two groups. In both groups our results showed age-appropriate normal values for ECG times (PQ, QRS, QTc) and heart rate at rest.

Worldwide, about 6 million people have experienced PCS so far, which makes PCS a relevant public health issue (8). 25% of 80,071 children with SARS-CoV-2 infection were affected by LC, with the most frequently reported clinical complaints being mood symptoms (16.50%), fatigue (9.66%), and sleep disorders (8.42%) (9).

PCS is nowadays considered a multisystemic condition of persistent symptoms following resolution of an acute severe acute SARS-CoV-2 infection. While this syndrome spans multiple organ systems, cardiovascular complications are often the most prominent features in adults, and include, but are not limited to, myocardial injury, heart failure, arrhythmias, vascular injury/thrombosis and dysautonomia (2, 10). Adult PCS patients have systemic inflammation and immune dysregulation compared to fully recovered Covid-patients. In particular, CD4+ and CD8+ positive T-cell numbers and SARS-CoV-2 antibody concentrations are increased in the peripheral blood of PCS vs. non-PCS patients, and there is mis-coordination between their SARS-CoV-2-specific T- and B-cell responses (11). In a large, prospective Long-Covid study, adult PCS patients (N = 346) showed mild functional impairment in several CMR variables (RVEF, LVEF). RVEF was significantly lower in PCS vs. 95 control subjects (54.0 ± 5.6 vs. 56.0 ± 5.8; p = 0.002), but only 1.4% had truly abnormal RVEF values, which is consistent with our pediatric study. The majority of adult PCS patients showed persistent cardiac inflammation in T-1 and -2 Mapping but normal serum hs-troponin T concentrations (12). Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved (12). However, it should be taken into account that even mild impairment in myocardial integrity and cardiac function over longer periods of time could have cumulative effects, decreasing physical fitness, that affect quality of life and long-term somatic and mental health. A recent meta-analysis of PCS in children and adolescents with symptoms for 4–12 weeks or ≥12 weeks (n = 80,071; 21 studies), reported the prevalence of PCS (LC) was 25.24%, and the most prevalent clinical manifestations were mood symptoms (16.50%), fatigue (9.66%), and sleep disorders (8.42%) (9). Our study is somewhat limited as we performed deep standardized cardiovascular phenotyping in consecutive children with PCS at the time of diagnosis, but not at a later timepoint. The long-term consequences of the moderate impairment of RV contractility and altered RV morphology (increased RV mass) after SARS-CoV-2 infection are not yet fully understood. A possible association between the cardiac dysfunction and specific coronavirus variants or vaccination are unknown. In our study, patients were not differentiated according to virus variant, vaccination status and severity of initial infection, which limits our study regarding a potential risk stratification. The limited number of controls in our study may introduce potential biases and reduce the statistical power. Future studies with larger control cohorts and comprehensive assessment of relevant risk factors should include multivariable modelling using binary logistic regression to improve the statistical power. Taken together, Post-COVID syndrome in children and adolescents is associated with decreased CMR-based radial and circumferential RV contractility (RVGRS, RVGCS) and increased RV mass, compared to healthy, age/gender matched controls. In contrast, LV contractility (strain) and mass were not affected. CMR-based tissue tracking (strain analysis) appears to be more sensitive than echocardiographic strain analysis in detecting abnormal myocardial contractility. Whether the aforementioned RV alterations are causal for the reported cardiopulmonary exercise limitations in pediatric PCS is unknown, and should be investigated in future studies. In view of the current data, it is crucial that children with SARS-CoV-2 infection or PCS undergo comprehensive cardiac diagnostic evaluation and follow-up to identify and treat potential complications at an early stage. Future studies should focus on understanding the mechanisms of altered cardiac function and morphology in order to develop appropriate intervention strategies.