Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study

Abstract

Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1, p = 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms, p = 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms, p = 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms, p = 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography. Conclusion: These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies. What is Known:• Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms. What is New:• Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults.

Cardiopulmonary Exercise Testing in Children With Long COVID: A Case-controlled Study

“…All together, these events may possibly be the cause of the abnormal cardiovascular efficacy we documented at the CPET of children with LC. These data would suggest that the recognition of specific subphenotypes at CPET (eg, suggestive of dysautonomia) can suggest the need to assess heart rate variability, as we have documented in a previous case report and in a larger original study 13 , 36 and recognize syndromes associated with inappropriate tachycardia, which are potentially treatable, also in children. 41 Obviously, more studies are needed to validate our observations.…”

“…Studies in adults, in fact, found that cardiac autonomic dysregulation is a major cause of exercise intolerance, leading to findings of cardiovascular limitation at CPET. 35 In another study, 36 we documented significant differences in heart rate variability of children with LC compared with controls. Modulation of the HR during exercise is a dynamic process tightly regulated by the autonomic nervous system and its imbalance may manifest during exercise as chronotropic incompetence or inadequate HR recovery.…”