Clinical characteristics, activity levels and mental health problems in children with Long COVID: a survey of 510 children

Danilo Buonsenso, MD, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy Ferran Espuny Pujol, PhD, Clinical Operational Research Unit, University College London, London, UK Daniel Munblit, PhD, Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia Sammie Mcfarland, Founder of Long COVID Kids, UK Frances K Simpson, MSc, Coventry University Group and Long COVID Kids, UK


Background
One year after the first description of SARS-COV-2 in China, several results have been achieved in the understanding of epidemiology and physio-pathological bases of  (1) and its treatment (2), and a number of effective vaccines have been developed and marketed (3). However, unexplained issues still remain. Among them, a particularly debated issue, by both patients and researchers, has been the recognition that a relevant percentage of patients with COVID-19 experience persisting symptoms after the resolution of acute disease. While patients relatively quickly highlighted their persisting symptoms and change in quality of life, Italian researchers first documented this on an International peer-reviewed journal (4). Carfì et al found that in patients who had recovered from COVID-19, 87.4% reported persistence of at least one symptom, particularly fatigue and dyspnoea. Later, several other papers confirmed these data in adults and a recent large cohort of 1,733 patients from Wuhan found persistent symptoms in 76% of patients 6 months after initial diagnosis (5).
Since this condition is still not completely understood, a definite official name was not initially recognized. Nevertheless, patient organizations started complex discussions and movements on social media with various kinds of evidence and advocacy to demonstrate a longer, more complex course of illness than laid out in initial reports from Wuhan and, eventually, coined the term Long COVID (6) which was, later, also recognized by the World Health Organization (7). Long COVID is probably the first illness named directly from patients.
Researchers have only recently began to study why people develop these symptoms.
According to the WHO, several explanations can be considered (7): persistence of the virus in some parts of the body that are sheltered from the immune system, such as the brain; direct damage to organs, such as the heart and lungs, and also the pancreas, causing some new cases of diabetes; and blood clotting, which can cause heart attacks and strokes.
However, there is a huge variety in both the pattern of symptoms and their severity, with gender and, possibly, age differences.
While at the beginning children were considered relatively spared by the pandemic, around December parent movements began highlighting that most children never recovered from acute COVID-19. Parents developed social media movements aiming to highlight that children were also suffering from Long COVID. The Long COVID Kids UK (https://www.longCOVIDkids.org/) began initially with the launch of an online message on YouTube on October 31 st 2020 (https://www.youtube.com/watch?v=RiIambG8vs0) and with Facebook and Twitter channels. Since its start, 197,000 people have been reached on Facebook and 1.8 million interactions on Twitter. So far, the group includes over 1,800 children from 1,332 families (Appendix figures). Later, a case series from Sweden described a group of five children with Long COVID (8). A larger study from Italy confirmed that about one out of three children with acute COVID-19 experienced persisting symptoms months after initial diagnosis (9).
Considering the importance of patient-driven data in this pandemic and for the understanding of Long COVID in particular, and aiming to provide more insights in the burden of Long COVID in children, one of the largest parent movements (Long COVID Kids UK) performed an online follow-up survey of a large cohort of children that experienced COVID-19 and had persisting symptoms.

Long COVID Kids Rapid Survey 2
In order to assess the presence of persisting symptoms in children with previous COVID-19, the parents non-profit association LongCOVIDKids developed an online platform where parents from all over the world can access and anonymously report their child's experience.
The 'Long COVID Kids Rapid Survey 2' was designed as a follow-up to a pilot survey (that established quantity and type of symptoms) as a means to establish clusters of symptoms rather than the full breadth of symptoms as well as the effects on the mental and physical health of the child as a result of Long COVID. Certain symptoms were deliberately excluded as they were not considered relevant to the clusters under consideration. Links to the survey site on JotForm were disseminated on the closed Facebook group LongCOVIDKids. Parents' consent was required before answering questions on their children with COVID-19 persistent symptoms.
In the 'Long COVID Kids Rapid Survey 2', participants were asked to self-declare the following main information on their children: how COVID-19 was confirmed and details at Committee was not necessary for this study.

Data Analysis
The Confirmation status of COVID-19 infection was asked about as "Has your child had confirmed or suspected COVID-19 infection?". The possible answers to that question were: "Clinical Diagnosis", "Lateral Flow", "Positive PCR Swab", and "Unconfirmed by a test or medical professional but we think we had it." We will initially report the counts for the original possible answers, and then in tables we will use a simplified version by merging "Positive PCR Swab" and "Lateral Flow" as "Positive Test". Time from infection was estimated We produced summary tables and graphs aiming at the description of the study sample, the symptoms and changes in Long-COVID children, looking further at changes in their physical activity levels and mental health. We cross-tabulated variables by confirmation status of COVID-19 infection and by the pre-existence of comorbidities.

Study Sample
Data on 510 children who had had COVID-19 for more than 4 weeks were reported by their  (Table 1).   Table A1. 411 (80.6%) children had no pre-COVID mental health concern or diagnosis.

Persistence of symptoms in children since COVID-19
Overall, children had persisting COVID-19 for a mean of 8.2 months (standard deviation 3.9) ( Figure 1, right). Details of reported symptoms are described in Table 2

Long-COVID children have suffered complex changes since COVID-19 infection (Figure 2 and
Appendix 49.6%). The latter changes were significant on children with confirmed/unconfirmed COVID-19 and occurred similarly on those with or without pre-existing conditions ( Figure 2 and Appendix Table A3). Overall, all children have had at least 1 change and 325 (63.7%) children have had at least 4 changes from those in Table 4 since their COVID-19 infection.
The proportion of those with at least 4 changes is above 60% independently of whether they had had pre-COVID conditions (Appendix Table A4).

Changes in Physical Activity Levels
Most children were physically active before their COVID-19 infection. During the first 6 weeks after infection, 262 (51.4%) children did participate in some level of activity, 217 (42.5%) did not, and for 31 (6.1%) children their parents were unsure.
Families reported that their children activity levels were worse than before infection (Appendix tables A5 and A6). Only 51 (10%) children have returned to previous levels of activity. 108 (21.2%) are currently unable to enjoy any activity, and 154 (30.2%) enjoy occasional activity but usually have an increase of symptoms after. Overall, the more physically active they were before COVID-19, the higher the proportion of them who returned to previous activity levels, although these rates are very low: only 17 (11.8%) of those who practiced daily sports before COVID-19 returned to previous levels.

Changes in Mental Health
Parents reported a significant prevalence of Neuropsychiatric symptoms among their children with persisting symptoms (Figure 3 and Appendix and 132 (25.9%) children have had no issues (excluding "None of the above" and "Other").
Only 64 (28.7%) of those with no pre-COVID conditions haven't had any mental health/cognitive issues since their COVID infection (Appendix Table A8).

Discussion
In this study, we performed a comprehensive assessment of parents' perspectives about long-term physical and mental health outcomes of a large cohort of children with persisting symptoms after initial COVID-19 infection, providing details about reported symptoms, their dynamics and the overall changes in children activities and mental health.
We found that fatigue, headache, muscle and joint pain, post-exertional malaise, rashes, heart palpitations were commonly reported by parents. and sore throats months from initial diagnosis. While some had improved after 6-8 months, none had fully returned to school. Interestingly, the UK, Italian and Swedish patients had similar age patterns. Of note, adults' studies on Long COVID report a very similar pattern of symptoms as well (4,5). The similarity of the reported symptoms in different cohorts of adult and paediatric studies suggest that those may be the defining symptoms of Long COVID in general, including in children.
In this survey, we assessed symptom dynamics. This is an important aspect of Long COVID according to descriptions of patient organizations and adults' studies, while it was not assessed in children before. Interestingly, we found that 25.3% of children have suffered constant COVID-19 infection symptoms, 49.4% have had periods of apparent recovery and then symptoms returning, 19.0% had a prolonged period of wellness followed by symptoms.
Importantly, a similar pattern was reported independently in those with and without preexisting conditions. To date, we did not find any paediatric study to compare our data.
Since physical activity plays an important role in child health, growth, development and socialization, we assessed how it changed after the infection of COVID-19. Overall, we found that most children had worse activity levels than before infection, since, at the time of the survey, 21.2% were currently unable to enjoy any activity and 30.2% enjoyed occasional activity but usually had an increase of symptoms after. Although lockdown and school closure may have contributed to this change (10), from our survey it seems that physical conditions were the main limiting factor for not enjoying physical activity.
We also assessed mental health issues in this cohort of children with previous COVID-19.
During the last months of the pandemic, healthcare professionals seeing an increase in suicide attempts and other issues related with mental health in children and adolescents have raised several warnings (11,12). Parents reported a wide range of neuro-cognitive symptoms, including lack of concentration, difficulty processing/remembering information or understanding instruction, short term memory issues and struggles to find the right words. Similar problems have been reported in the only paediatric study performed so far (9) and in several adult studies (4,5).
This study has several limitations to address. First, it is an online survey that was only shared through an online platform and not systematically proposed to consecutively diagnosed children within specific settings, therefore determining a selection bias. Also, this survey has been launched on the page of Long COVID Kids UK, which was created with the purpose to provide awareness and support to families with children with Long COVID. Therefore, parents of children with persisting symptoms may have had more interest in participating in this survey, and this can explain the large number of children with persisting symptoms in this cohort, when compared with other cohorts. Therefore, we were not able to define the incidence of Long COVID in children. Another limitation is that not all children received a microbiologically confirmed diagnosis. This is mainly due to unpreparedness of health systems (13) and difficulties in access to test, particularly during the first months of the pandemic, and because of different decision-rules practices in different settings. Also, the small number of children requiring hospitalization did not allow us to determine how initial severity affected long COVID in children. Last, the lack of a control group cannot allow us to determine a cause-effect link between COVID-19 and these symptoms. Conflict of Interests: SM and FKS are co-founders of Long COVID Kids UK. While they developed the survey and were responsible to share the page online, they had no role in the data analysis, which was performed independently by DB and FEP.
Funding: Nothing to declare.   Table A5. Activity level before infection by Participation in Any level of activity in the first 6 weeks of COVID-19 infection   Table 5, excluding "None of the above" and "Other"), by confirmation status of infection, and by the pre-existence of comorbidity conditions