This study evaluated whether changes in the routine of children and adolescents during the period of social isolation resulting from the COVID-19 pandemic had any impact on anthropometric data, quality of life, and possible subclinical changes suggestive of arterial stiffness in this population. To the best of our knowledge, this is the first controlled study where cardiovascular variables and QoL were compared in similar populations in the pre- and post-pandemic periods. This study demonstrated that the main subclinical marker of arterial stiffness in the paediatric population, represented by AIx@75, which is a highly predictive variable of cardiovascular events [26], was increased in children and adolescents after one year of social isolation.

The period of social isolation resulting from the COVID-19 pandemic can be considered a toxic childhood environment due to the various negative changes that occurred during the period, especially for children and adolescents [39]. The link between psychological factors and cardiovascular health has been long studied. Epidemiological data show the effect of negative psychological states on the cardiovascular system, linking depression, perceived stress, anxiety, and hostility to increased cardiovascular risk [40]. Stress influences circulating inflammatory markers, and these effects may mediate the influence of psychosocial factors on cardiovascular risk [41]. In a review study, Steptoe et al. showed robust effects for increased levels of circulating of IL-6 and IL-1beta following acute stress, and marginal effects for C-reactive e protein. A number of psychobiological mechanisms may underlie responses, including stress-induced reductions in plasma volume, upregulation of synthesis, or enlargement of the cell pool contributing to synthesis [41]. Acute systemic inflammation leads to a temporary increase in large-artery stiffness in healthy populations [42]. Recent study shows that early life adversity, depression, and obesity are associated with increases in low-grade inflammation in adolescents [43]. Chronic inflammation has been shown to have a role in pathogenesis of atherosclerosis [44].

The pandemic has drastically affected the routine and habits of the general population [1, 3]. The decrease in the practice of physical activities or sedentary lifestyle, associated with harmful eating behaviours, has already been demonstrated in children and adolescents, which increased the risk of obesity [45]. In our study, weight and BMI did not differ significantly between groups. In contrast, the HC was significantly higher in the APG, without, however, any difference in the WC/HC or WHtR indices that are used as predictors of metabolic and cardiovascular alterations [46]. Similar to our study, Rúa-Alonso et al. [47] compared the body composition of two independent samples of children and adolescents obtained from a database before and during the COVID-19 pandemic. These authors observed higher values of BMI, WC, HC, and WHtR in the post-pandemic group. In a longitudinal study, Jarnig et al. evaluated 708 children aged 7 to 10 years before and during the pandemic and found increased WC/HC and WHtR [48]. BMI has also increased significantly during the pandemic and as a result, the number of overweight, obese, or extremely obese children has increased from 15.0 to 21.2%, representing a relative increase of 41.3%. In another longitudinal study, Ramos-Álvarez et al. observed an increase in BMI and percentage of fat in children aged 11 and 12 years, with no change in WC values in the post-pandemic period [49]. These studies show that there is still no consensus in the literature regarding the worsening of anthropometric values. In addition, many of these studies focused only on assessing anthropometric data and did not assess baseline physical activity level in the two periods studied. In our study, we showed a worsening in the baseline physical activity level, with an increase in the number of children considered sedentary and a decrease in the number of children considered active according to the IPAQ-C. However, despite a clear trend observed in the worsening of baseline physical activity level, we did not observe a significant difference between APG and BPG, which could be related to the reduced sample size of our study.

When comparing the QoL domains between the study groups, we observed a significant worsening in the emotional and school domains in the APG in relation to the BPG. The worsening in these domains was expected as the impact of the COVID-19 pandemic on the mental health of children and adolescents has been demonstrated in numerous studies [5, 50, 51]. During COVID-19 pandemic, most parents have found themselves forced to restructure their routines to balance working from home with parental responsibilities. Therefore, this sudden overload has subjected parents to stressful situations, potentially increasing the risk of emotional and behavioral problems in children [52]. In addition, long periods of social isolation observed in COVID-19 pandemic well known to be associated with avoidance behaviors, a deteriorating family relationship and more conflicts at home, which can drastically impact in the quality of life, mainly in emotional domains [53]. Other studies have reported depression and anxiety in children and adolescents during Covid Pandemic, which could be related to emotional domain evaluated QoL [50, 51]. This could be attributed to social isolation and loneliness experienced by this population during the critical period of the pandemic [50, 51]. In addition, the major change in study routine imposed by the pandemic has had important repercussions on school performance [5, 54]. An impairment in self-report quality of life has been shown, especially in school and psychological domains [55].

We found two studies in the literature that correlated a worsening in QoL in children and adolescents with an increase in arterial stiffness. Santos et al. found no association between QoL in healthy children and adolescents and AIx@75 [19]. In contrast, Rossi-Monteiro et al. showed an association between worsening QoL in children aged 3 to 10 years with obstructive sleep-disordered breathing and an increase in PWV [20]. For the adult population, however, it has already been established that worsening in QoL is associated with an increase in arterial stiffness rates [56,57,58].

The main objective of the present study was to assess whether arterial stiffness indices, PWV and AIx@75, would be altered in the study population one year after the COVID-19 pandemic. Some studies have already evaluated non-invasive arterial stiffness markers in the young population, due to the high predictive value of this variable for the development of cardiovascular diseases. Shiraishi et al. showed that central blood pressure values measured with the Mobil-O-Graph® are accurate in children and hold promise as markers of cardiovascular risk in the paediatric population [37]. Several studies show standardisation of values of the main arterial stiffness indices in children and adolescents, both by traditional methods of measuring carotid-femoral PWV and brachial artery flow-mediated vasodilation, and by indirect systems derived from algorithms calculated from brachial artery oscillometry [19, 59, 60]. Torigoe et al., amongst others, reinforced the importance of using arterial stiffness markers in children and proposed reference equations for AIx@75 values in different clinical conditions [60]. Thus, we asked whether these markers could be altered in the paediatric population, since the major change in routine imposed by the pandemic radically changed eating habits and physical activity, which are factors clearly associated with important changes in the cardiovascular system.

In the present study, we showed that the main determinant of arterial stiffness in children, AIx@75, was significantly higher in APG participants. Since our groups were matched by sex, age and socioeconomic class, our data suggest that conditions associated with routine changes resulting from the COVID-19 pandemic, such as changes in QoL due to alterations in eating habits, emotional changes, and decreased physical activity, could lead to early changes in vascular architecture and functioning. In addition to AIx@75, PWV has been shown to be a good marker of arterial stiffness. However, some authors have shown that PWV is not an adequate marker in the paediatric population, despite being important in adults [61, 62]. Some authors even describe that AIx is not linearly associated with PWV and argue that this phenomenon can be modulated by ageing, inflammation, and increased activity of the autonomic nervous system [63]. It has been reported that in the young population, AIx increases with age, whereas aortic PWV does not [61]. This is justified because the increase in AP would be due to an increase in the magnitude and not in the velocity of the reflection wave. Thus, several studies have shown changes in AIx@75 without significant changes in PWV in children, which corroborates our findings [19, 20, 24, 26, 35]. The inverse of this process occurs in older individuals, where PWV increases and AIx changes slightly, which suggests that the increase in AP would be driven by an earlier return of the reflected wave and a less compliant aorta rather than predominant changes in the magnitude of wave reflection [18, 61]. It is expected that in situations where there is an increase in AIx, the DBPc will be reduced, as was observed in our study of the APG. This happens because the early return of the reflected wave leads to a lower DBPc in the aorta [64, 65]. The decrease in DBPc is related to lower perfusion of important vascular beds such as the brain and coronary arteries, which is speculated to cause long-term dysfunctions in these tissues [64].

In the present study, an increase in HR was observed in the APG. Wilkinson et al. demonstrated that there is an inverse and linear relationship between AIx and HR resulting from changes in the time of the reflected wave caused by reductio in the duration of systole [66]. This increase in HR observed in the APG in our study may also have attenuated the increase observed in AIx@75. This change in HR could reflect changes in the physical activity routine and emotional changes experienced by the study population. We found a single study that proposed to assess resting HR in adult individuals with worsening emotional parameters or physical activity resulting from the COVID-19 pandemic before, during, and after the lockdown [67]. These authors showed an increase in resting HR during and after imposed restriction measures [67]. We believe that this can also be extrapolated to the paediatric population and would corroborate our findings.

Another factor that may have also limited the increase in AIx@75 in the APG was the reduction in TVR. Kelly et al. demonstrated that vasodilator drugs that reduce TVR are related to a decrease in AIx@75 [68]. Another parameter that deserves attention is SV, which was reduced in the APG. However, the CO was similar in both groups since the APG presented with higher HR.

The non-observance of major anthropometric changes between the two study groups does not mean that social isolation and restrictive measures imposed by the pandemic have not actually contributed to an increase in the cardiovascular risk of children and adolescents in the study. In adult patients, anthropometric data, including BMI and abdominal and hip circumferences, are related to increased arterial stiffness and mortality from cardiovascular events [46]. However, no correlation has been observed between these anthropometric data and the increase in arterial stiffness in healthy children and adolescents [19, 60]. Thus, some studies have pointed out that anthropometric measurements of body composition do not adequately reflect cardiovascular risk in the paediatric population.

Our study has several strengths that should be highlighted. First, although our comparisons were made in two independent samples, children and adolescents were matched by sex and age and socioeconomic class. Second, according to the sample calculation, 60 participants would be needed in each group and our study eventually included 89 and 104 participants in the BPG and APG, respectively. One of the limitations of the study was the sample selection. The BPG was selected from nine representative regions of a large metropolitan city and the ABG was selected from only two regions. Another limitation was the use of BMI as a measure to interpret weight variation. Body composition can be highly variable and still yield the same BMI. In addition, BMI does not provide information on the regional distribution of body fat.

Although volunteers who reported being positive for COVID-19 infection were excluded from the study, some children may have been previously infected and undiagnosed, as this type of infection shows few clinical signs in the paediatric population. This may have influenced the observed results.