Imperative to alleviate Long COVID in children

Little is currently known about children who develop prolonged symptoms after a COVID-19 infection. Besides tiredness and shortness of breath, which is seen in all age groups, these children experience other symptoms that are not always clear-cut. Furthermore, the symptoms differ per age group as well. For example, the symptom pattern in children up to the age of 12 presents is different from that in older children. Young children suffer more from symptoms such as stomach ache, diarrhoea, nausea, vomiting and temperature dysregulation or fever. Older children often experience concentration problems, headaches, and taste and smell problems. At the start of this VINCERE study, we therefore decided to divide the participants according to age: from 6 to 12 years, and from 12 to 18 years. Eventually, 110 participants from throughout the Netherlands were included in the space of 18 months.

Due to an intensive collaboration with hospitals in Rome, the number of participants further increased to 300. In so doing, we found that the pattern of symptoms in Italian children often agreed with that of Dutch children. This European collaboration in the area of Long COVID in children is valuable. Besides achieving clinical consensus, this also creates a platform which allows us to easily share research results and bring them into the clinic.

It was assumed that a vaccination for children from 12 to 18 years, who experienced prolonged symptoms after a COVID-19 infection and developed Long COVID, could result in an improvement. Initially, we intended to realise our own vaccination study among children. However, at the start of the study, the Dutch government also invited the children to participate in the COVID-19 vaccination programme. Therefore, many children with Long COVID  already received a vaccination. With the VINCERE study, we eventually managed to describe Long COVID in children, including the type of symptoms and their impact on everyday functioning. For the final analysis, we want to examine whether vaccination has (had) an influence on Long COVID symptoms as well.

Including children with Long COVID is a major challenge. The aim was to include 100 children up to 12 years of age, and 100 from the age of 12 onwards, but that proved to be more difficult than thought. The travel distance to the research location and the severity of the symptoms meant that participating in this study was quite an effort for the children. They are very tired and can often hardly go to school, if at all. Despite the symptoms, they are often still prepared to participate in our study. An important reason for participating is that they want to help to find answers to the questions associated with this clinical picture. Fortunately, by seeking collaboration with Italy, the numbers desired for the study could be obtained.

Most studies into Long COVID have been done in adults, so it is important to describe this clinical picture in children as well. Children are physically different from adults, and their response to a virus infection also differs from that of adults. From Amsterdam UMC, an international network has also been set up to discuss difficult cases. In addition, there is a manual for recognising, diagnosing and treating Long COVID. This arose from a national collaboration between various disciplines. In this VINCERE study, we have collected many tissue samples, such as blood and faeces, for testing. As part of these tests, we specifically examine the immune system and so-called biomarkers (signalling substances) in blood, as well as bacteria in the faeces. This data clarifies the body's response and can hopefully provide us with more insight into the similarities or differences compared to adults who have Long COVID.

The ultimate aim is to better recognise Long COVID in children. This is why we are searching for divergent biomarkers in these children. Ultimately, we might be able to target the treatment for these children at those biomarkers. Given the impact of the clinical picture on the individual functioning of children and with that, on society, it is important to gain more insight into this clinical picture with the ultimate aim of a better treatment for this group of children. We intend to complete the VINCERE study by the end of 2023.