To our knowledge this is the first study to document prevalence, symptoms and duration of long covid in such a large national cohort study comparing RT-PCR verified SARS-COV-2 infected children to a control group of randomly selected children, who have not previously been tested positive for SARS-CoV-2.
In the present study, 12–51% of SARS-CoV-2 positive children experienced ‘long COVID’ symptoms. The age distribution of symptoms differed with older school children being more frequently affected compared to younger school- and preschool children. However, from an identical list of symptoms, 15–38% of children in the control group also reported symptoms lasting 4 weeks or more. Two previous pediatric studies reported that between 8–66% of children experience ‘long COVID’ symptoms [14, 15]. However, none of these studies included a control group. One pediatric study included a control group, but only had a sample size of 77 children experiencing symptoms lasting for more than 28 days, and as such could be categorized as ‘long COVID’ symptoms according to NICE guideline.
Comparing the responses from SARS-CoV-2 infected children to a control group, we found that the most common statistically significant ‘long COVID’ symptoms were fatigue, loss of smell and loss of taste, and to a lesser extend muscle weakness, chest pain, dizziness and respiratory problems. Loss of smell and taste have previously been reported as symptoms among SARS-CoV-2 positive adolescents  and adults.
During the COVID-19 pandemic governmental interventions have been introduced in order to reduce transmission of SARS-CoV-2. Quarantine regimes, increased hand hygiene, school and daycare lock down, closure of sports and leisure activities, and social distancing are among the numerous interventions. Reports have raised concern on the negative impact of these social implications on children’s mental health. Bearing this in mind it is crucial to compare reported long covid symptoms in previously SARS-CoV-2 positive children to a cohort representative of the background population. Describing ‘long COVID’ in a pediatric population without a control group could otherwise overestimate ‘long COVID’ symptoms.
Concentration difficulties, headache, muscle- and joint pain, cough, nausea, diarrhea and fever, have previously been described as ‘long COVID’ symptoms of SARS-CoV-2 infection in children in non-controlled trials[14, 15, 21]. However, we found that these symptoms were statistically more significant in the control group. Our study also documented that children in the control group had a lower WHO-5score compared to SARS-CoV-2 positive children. Therefore, it should be considered whether concentration difficulties, headache, muscle- and joint pain as well as nausea, could be symptoms reflecting the negative impact of the social implications of the pandemic on children’s mental and physical health. The reason for reports of more frequent fever occurrence in a randomly selected control group can only be speculated, since questions on specific method of temperature evaluation or accompanying symptoms were not included. In general, the first year of the pandemic have had a remarkably low incidence of otherwise high incidence infections, such as respiratory syncytial virus and influenza virus[22, 23]. We would therefore have expected a low occurrence of fever.
The duration of ‘long COVID’ symptoms is an important issue to address with implications for the children and families. In our pediatric cohort, most children recovered within a maximum of 1–5 months. Recovery time of 2 weeks-3 months have previously been described in non-controlled pediatric studies[14, 15].
We aimed to document whether ‘long COVID’ symptoms could reflect isolation, corona restrictions and lock downs. Our analysis showed that children presenting with ‘long COVID’ symptoms reported a higher sense of well being compared to children with symptoms who have never been tested positive for SARS-CoV-2. As such, fatigue, loss of smell and loss of taste, muscle weakness, chest pain, dizziness ad respiratory problems cannot be assigned to psychological sequelae of social restrictions but must be recognized as ‘long COVID’ symptoms.
There are significant limitations to this observational study. Firstly, our questionnaire was not validated in a larger pilot study. Moreover, data relies on participants' retrospectively parent- or self-reported symptoms with a risk of recall bias. However, SARS-CoV-2 is an infection with increased focus in society. As such, participants have possibly been extremely aware of symptoms during their infection, and therefore recall bias is assumed to be minimal. Secondly, the control group might include children who have had SARS-CoV-2 infection without having undergone testing. This is a risk since children have no or only few symptoms of acute COVID-19. Moreover, parents might be more reluctant to let children undergo testing due to the invasive and unpleasant procedure. Children in the control group have never been tested positive for SARS-CoV-2. Nevertheless, seroprevalence data suggest an infection rate of 2–3 times higher than corresponding PCR results in the pediatric population. The potential presence of children with previous SARS-CoV-2 infection in the control group would underestimate the symptoms of ‘long COVID’. Thirdly, it could be speculated that children in the control group and the SARS-CoV-2 group who experience symptoms are more eager to respond to the questionnaire than asymptomatic children. This could lead to selection bias and result in an overestimation of reported symptoms. However, the study may also suffer from non-response bias where non-symptomatic controls may be under-represented. The number of children answering the questionnaire was higher among SARS-CoV-2 positive children than in the control group (44.9% versus 21.3%). The higher response rate in the group of children with previous SARS-CoV-2 infection could be expected since these children and families might have higher awareness on potential ‘long COVID’ symptoms, and a potential increased desire for knowledge about long covid. However, in both groups, the children who answered the questionnaire were an equal age distribution of the children who received the questionnaire.
The strengths of this study are primarily the large sample size and inclusion of a control group. Additionally, the Danish Health Data Authority has a nationwide coverage, and all Danish citizens have universal tax-funded health insurance. Therefore our study population did not rely on access to health-care services, and RT-PCR tests for SARS-CoV-2 are free of charge in Denmark minimizing selection-bias. The infection status of all SARS-CoV-2 positive children has been established by nationally validated RT-PCR, eliminating major misclassification of infection status. Moreover, the results of the SARS-CoV-2 test are linked to the unique personal identification number registered in the Danish Civil Population Register and the national microbiology database making it a complete cohort of SARS-CoV-2 infected children below 18 years from the start of the pandemic in Denmark until 19th of March 2021.
The control group consists of randomly selected children age 0–17 years from five municipalities that include both larger cities as well as rural areas. As such, the control group is considered to represent the general Danish population of children. The strengths mentioned above increase the generalizability of our results. However, it is important to consider that an observational study based on a questionnaire with subjective responses and without objective examination of the children, can only provide us with one piece of the puzzle. Further studies are needed to increase knowledge of ‘long COVID’ in the pediatric population.
In conclusion, to date this study is the largest study on post acute effects in SARS-CoV-2 positive children also including a control group. It provides new evidence that symptoms of ‘long COVID’ in children are fatigue, loss of smell and loss of taste, dizziness, muscle weakness, chest pain and respiratory problems. These symptoms cannot be assigned to psychological sequelae of social restrictions. Symptoms such as concentration difficulties, headache, muscle- and joint pain as well as nausea may be related to other factors than SARS-CoV-2 infection. In most cases ‘long COVID’ symptoms resolve within 1–5 months.