Reply to: Letter on the Recent Paper “Vascular ‘Long COVID’: A New Vessel Disease?”

Dear Editor, We read with great interest the letter by Calcaterra and coworkers ¹ related to our publication entitled “Vascular ‘Long COVID’: A New Vessel Disease?” ²

The letter ¹ discusses Long Covid Syndrome in children and adolescents, highlighting how this syndrome, which is proving to be very frequent in adults, affects children to a lesser extent.

There is still little information in the literature on Long Covid syndrome in children, both due to poor diagnosis and lack of measurable biomarkers.

Literature on the prevalence of Long-COVID-19 in the pediatric population is scarce. Among 320 825 people with Long-COVID-19 Syndrome in the UK, .16% of cases were in children aged 2-11 years, .65% in children aged 2-16 years and 1.22% in those aged 17-24 years.^3,4 This is one of the reasons why it is quite difficult to predict which children will develop Long-COVID-19. Furthermore, in the vast majority of Long-COVID-19 studies, symptoms were reported by parents.^3,4

The symptoms of Long Covid Syndrome in children are very varied and include headaches, fatigue, skin rashes, non-specific respiratory symptoms, and gastrointestinal symptoms. This constellation of symptoms makes early diagnosis even more difficult. ⁵

Analyzing the risk factors for Long-COVID-19 in children according to the literature, a positive correlation was found between increasing age and symptoms of Long-COVID-19 as well as for female gender, allergies, and the presence of persistent symptoms. ⁴ In most studies, symptoms persisted for no more than 12 weeks, with an average of 8 weeks. ⁴

Dysregulation of the immune system, a hyperinflammatory state, and damage to the endothelium and microvessels are involved as pathogenetic mechanisms.^5,6 Furthermore, an impaired immune response appears to play a prominent role. These aspects were explored in our previous publications.^2,7

It should be remembered that the immune response undergoes a profound remodeling with aging. The immune system of children is characterized by a series of features (higher percentage of naïve T cells, higher number of regulatory T cells in the peripheral tissues, lower levels of proinflammatory cytokines, among others) that can partially explain the different long-term impact of COVID-19 in children.^5,6 Indeed we must not overlook the diagnostic suspicion of Long Covid Syndrome in a child. We thank Calcaterra et al ¹ for their thought-provoking observations on Long Covid Syndrome in children and adolescents. These age groups must be followed with attention. ⁸