Given that there is no universally agreed definition of Long COVID, we elected not to start with an arbitrary definition of a new condition but to seek the descriptions from almost 7,000 CYP of their physical and mental experiences in the months following a SARS-CoV-2 test. This is the largest study on symptoms post-COVID in children to date and, uniquely, uses child-reported symptoms, is confined to PCR-proven SARS-CoV-2 status, has a PCR-negative control group, and uses standardised measures to assess mental health, well-being, and fatigue.
Several important findings contribute to the current knowledge of Long COVID in CYP. First, three months after the SARS-CoV-2 test, the presence of physical symptoms was higher than at the time of testing. This finding emphasises the importance of having a comparison group to objectively interpret the findings and derive prevalence estimates. Although 64.6% of test-positives reported no symptoms at time of testing (compared to 91.7% of test-negatives), they did not continue to remain asymptomatic, with only 33.5% of test-positives (and 46.7% of test-negatives) reporting no symptoms at 3 months. This finding warrants further exploration and could be due to self-selection into the study because they were experiencing on-going symptoms, recall bias, external factors relating to the pandemic such as returning to school and exposure to other sources of infection, and the actual trajectory of the illness, although this wouldn’t explain the high prevalence among test-negative CYP.
Second, symptoms reported at time of testing among test-positives were sore throat, headache, tiredness and loss of smell while test-negatives had sore throat, headache, fever and persistent cough. The symptom profile does not distinguish test-negatives and test-positives. However, the two groups could be separated according to the number of symptoms at three months, when 30.3% of test-positives and 16.2% of test-negatives had 3 + symptoms, with tiredness and headache being common in both groups, but higher in the test-positives. Consideration of number of symptoms, rather than profile, is particularly important given that 53.3% of the test-negatives had at least one symptom 3 months post-test. These figures should be seen in the context of published norms. For example, high levels of fatigue have been reported in the general adolescent population with an estimated incidence of 30% in CYP aged 11–15 over a 4-6-month pre-pandemic period22.
Third, our findings showed that, for both test-positives and test-negatives, those assigned to the latent class with “multiple symptoms” at three months were more likely to be female, older and have poorer physical and mental health before COVID-19, suggesting that pre-existing physical and mental health difficulties may influence symptoms at three months. Unsurprisingly, those with multiple physical symptoms had poorer mental health, reflecting the close relationship between physical and mental health.
Fourth, whilst the prevalence of physical symptoms differed between test-positives and test-negatives, no differences were found in mental health, wellbeing and fatigue scores. The scores on the measures are broadly comparable to pre-pandemic published norms on the standardised measures23,24(https://sdqinfo.org/norms/UKNorm1.pdf). However, a large proportion (~ 40%) in both groups reported feeling worried, sad or unhappy. This is consistent with parent-reported surveys of mental health of CYP during the pandemic25 and highlights the need for mental health interventions26 for parents and CYP regardless of COVID status. The findings emphasise the importance of incorporating a comparator matched cohort of test-negative CYP who have contemporaneously experienced a pandemic, school closure and social isolation.
Despite a need to estimate Long COVID prevalence in CYP, this first requires an evidence-based case definition27. Our findings indicate that any definition of Long COVID should consider multiple symptoms and, as in adult studies on Long COVID, there may be different clusters of symptoms28. Given our findings of multiple, varied symptoms three months after infection, it seems a multi-component intervention will be required, building on existing interventions for management of problems such as headache and fatigue.
Our findings should be seen alongside the CYP literature. The commonest symptoms reported at three months in test-positives of tiredness, headache, shortness of breath, dizziness and anosmia are consistent with Molteni, et al. 1 where parents reported symptoms ≥ 28 days (fatigue 84%, headache 80% and anosmia 80%). They also reported that persistent symptom prevalence was higher in girls, teenagers and children with long-term conditions. The ONS survey6 describes population prevalence rates of persisting 'symptoms more than 4 weeks after COVID-19’ whereas the present study gives rates in a test-positive population; hence apparent differences may be attributable to differences in definitions and methodology.
Taking the studies together, there is consistent evidence that some teenagers will have persisting symptoms after testing positive for SARS-CoV-2 and that mental and physical health symptoms are closely related. Avoiding false dichotomies between mind and body is likely to be helpful as, for example, stressed individuals may present with somatic symptoms or conversely persisting physical symptoms may be associated with depression and anxiety. Some individuals may develop somatic symptoms disorders29 and the existing evidence for effective management of conditions such as pain, headache and fatigue30 might be usefully evaluated in CYP presenting with persistent physical symptoms post-COVID. CYP with clinically impaired mental ill health should receive the appropriate evidence-based treatments whether or not they have physical symptoms. Family approaches and understanding of persistent symptoms is key31. Investigation of persisting symptoms may be needed or requested, with consideration of the potentially negative impact of protracted medical treatments or investigations if no abnormalities are found29.
This study has limitations. PCR-testing can result in some false negative and false positive results and we were unable to independently determine whether the test-negatives had previously had COVID unless they had been tested although this is likely to account for only a minority of cases. We could not recruit based on ethnicity as this was not recorded at time of test but ethnicity was very similar in test-positives and negatives (Table 2) and geographical region served as a proxy for socio-economic status; both these variables are thought to influence COVID in adults and could be important in Long COVID32. As in any self-selected online study, we need to acknowledge our response rate of 13.5%. It is possible that there is a response bias for example, towards those continuing to experience symptoms at 3 months being more motivated to participate, resulting in an over-representation of symptom prevalence. It is also possible that recall bias influenced the reporting of symptoms at the time of testing as well as physical and mental health prior to testing, in particular, if tested positive. However, we tried to minimize the impact of this bias by only considering CYP that reported on baseline ~ 3m later. We did not assess whether symptoms were continuous for the entire 3 months, or whether they waxed and waned. Finally, the experiences of the CYP in January, February and March were likely to be highly varied with regard to school closure. At the time of testing, schools were closed, while, at 3 months after testing, schools had reopened albeit with social distancing, repeated testing and restriction of activities. Schools can be a source of both stress and support, and the return to school may partly explain some of the findings, in particular, the higher prevalence of symptoms at 3 months compared to baseline. The responders are largely representative of our target population though we have over-representation of girls and older CYP, with under-representation from North-West England and London. Inclusion of the comparator group was essential to place the findings within the wider context of the pandemic.
These data also reflect symptomatology at a time when the Alpha variant was predominant in the UK. Whilst these findings may change with different variants, the prospective nature of this study makes it uniquely placed to detect such changes across the pandemic waves.
In summary, post-COVID is different in CYP to adults and one should not extrapolate from the adult literature to decide policy and services for CYP. Our research demonstrates (1) the importance of having a control, test-negative group to interpret findings and prevalence estimates, (2) that it is essential to consider multiple symptoms in any clinical phenotype of Long COVID, (3) that mental and physical health symptoms should both be considered, (4) PCR-proven SARS-CoV-2 positive CYP had a higher frequency of any symptoms and multiple symptoms three months post-test than test-negatives. These results would have been very difficult to interpret without a control group and laboratory-confirmed SARS-COV-2 status. Hence, prevalence estimates and definitions of Long COVID should consider the presence of multiple symptoms, proven SARS-COV-2 status and include control groups. We will use these data and a Delphi consensus process to formulate a research definition of long COVID in CYP and will follow up the CYP over time to understand the long-term course in SARS-CoV-2 positive CYP.
This paper does not provide an evidence base for management of Long COVID or for any infective/immunological mechanisms underlying it. More research is needed.