This is a very well conducted exploration of the symptoms experienced by children and young adults aged between 12 and 17, after a positive test for COVID in the early part of this year, compared to a cohort of adolescents who tested negative.  It reports that almost one in three adolescents with a positive PCR for COVID had multiple, non-specific symptoms 3 months after the diagnosis, just less than twice that of younger adults who tested negative (30.6% compared to 16.2%).  This is in contrast to the recent publications from King’s College London that suggest that only 1.8% of these younger people experience Long Covid symptoms.  There are several potential explanations for this.

The first is “Reporter bias” – only people with something to say respond to questionnaires.  13.3% of the population responded to the questionnaire, which is a very good response rate in itself.  However, if we assume that of the 86.7% that didn’t respond none had symptoms (an extremely unlikely assumption) that still results in ~4% of the adolescent population having long Covid (30.6% of the 13.3% that responded).

A second difference is the proactive nature of this study.  Rather than relying on a parent to report symptoms by proxy, this study actively sought out symptoms.  People are more likely to recall or respond when prompted than volunteer information, particularly when that information is “by proxy” – i.e. someone else completing the forms on your behalf.

A third difference is in the time frame.  The King’s study looked across the timeline of the whole pandemic, whereas this study was just focusing on January-March this year.  There were differences in the nature of the virus, with the Alpha variant being dominant for the Clock study as opposed to a mixture of the wild-type and the Alpha variant for the Zoe.  We know that the Alpha variant is more infectious and more likely to be associated with hospitalisations that the original wild type variant.  It may also translate into more cases of long Covid, in adolescents at least.

In my view the results of this report, gives justification for Long Covid to be a significant consideration for the JCVI as they evaluate the role of vaccinating adolescents against Covid.  So far the focus for that discussion has been on the impact in reducing spread, acknowledging that adolescents get only minor symptoms of acute covid.  The results of this report, in my view, lends weight to the argument that vaccinating adolescents, reducing Covid infection and transmission, may also confer direct benefit by preventing infection and long symptoms that will impair education and learning as well as overall wellbeing.

There are some significant limitations in this study that may, if anything, under-estimate the effect that this is Covid is having on adolescents.  The “control” population were adolescents who tested negative.  This does not factor in the reason why those individuals had a test in the first place.  In the early part of this year, the key indicator for a PCR test was symptoms of a viral illness, compatible with Covid.  Thus it is reasonable to assume that all of the “negative” patients had another viral illness.  The key finding therefore is that Covid is associated with twice the incidence of post viral syndromes compared to other viruses.  Further, this analysis was based on positive tests from January to March of this year, before the Delta variant was dominant within the UK.  We know that the Delta variant is more transmissible amongst adolescents and is causing more significant disease in this population (https://www.cdc.gov/coronavirus/2019-ncov/variants/delta-variant.html).  A more significant disease in this population is likely to be associated with more post viral syndrome, although we will need to wait to determine whether that is indeed the case.

The CLoCK study clearly demonstrates that children and young people are susceptible to persistent symptoms following COVID-19 infection, and that a significant number remain affected even 15 weeks after their infection, when compared to a control population of children who tested negative for COVID-19.  

What is particularly important to note is that there was no difference in the mental health and wellbeing scores between the two groups, demonstrating that Long Covid in children and young people is not solely a result of anxiety related to the pandemic, but a very real physical condition resulting from infection with SARS-COV2.  In those children worst affected it will further exacerbate their already disrupted education during the pandemic, through absence from school and difficulty concentrating on school work, as well as impacting on their physical fitness through difficulty participating in school and team sports, and impacting on their parents’ ability to attend work while needing to care for their children.

 For this reason in my view it is important that Long Covid be considered amongst the other negative outcomes of COVID-19 infection (death and hospitalisation) when decisions are made in regard to protecting the population from COVID-19, particularly in relation to extending COVID vaccination to our younger population.

“This study on persistent physical and mental symptoms post Covid in children (11-17 years) is a very welcome addition to the growing evidence base, which is needed towards establishing working definition(s) for Post-Covid syndrome(s) or ‘Long Covid’ in children.  It was conducted during January to March 2021 when the alpha variant was dominant.  It has many strengths in that is nationally representative, is the largest to date with 6804 children (3065 positive for SARS-CoV-2), and has a 3 month follow up post testing date (with child report questionnaires).  The biggest strength is that it has a test negative and matched cohort.

“Similar to the King’s Covid symptom Zoe study, the most common symptoms were headache, tiredness, sore throat and loss of smell.  Interestingly 30% testing positive had multiple (3+) symptoms at onset and at 3 months; which was 5 times higher than test negative cases at baseline, but dropped to less than twice as common to test negative cases at 3 months.  This suggests that children are recovering, and also highlights the importance of having a control group.  Its survey design means that it may be subject to selection and recall bias (data not collected in real time), but the large sample size and detailed questionnaires somewhat negates that.

“Perhaps the most striking finding of the study is that with more detailed questionnaires about functioning, both positive and negative groups had the same level of fatigue scores, a key symptom in post viral syndromes.  There were also no difference in mental health symptoms, although both groups had relatively high emotional symptoms (~ 40% in both groups reported feeling worried, sad or unhappy), possibly indicating the significant effects of the pandemic and lockdown effects.

“With regards possible markers for multiple symptoms – being female, older, and poorer baseline physical and mental health were important risk factors.

“The importance of the interaction of the mind and body was shown in those with multiple physical symptoms having poorer mental health.  The importance of a holistic approach and acknowledging a mind-body interplay, has been an ignored aspect in medical care.  This suggests that more resourcing is hence likely needed to integrate mental health professionals working alongside multi-disciplinary physical health teams.”

Reference: Molteni, E., et al. Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2. The Lancet Child & Adolescent Health (2021).

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“This is a carefully designed and conducted piece of work that adds significantly to what we know about the later effects of COVID-19 infection in some children and young people and, importantly, the differences found compared to adults.  It demonstrates the need to differentiate how services for affected children and teenagers, as opposed to adults, should be conceived and delivered.

“It also highlights, perhaps unexpectedly, the high frequency of symptoms suggesting mental health issues in the older children studied, especially girls, regardless of prior COVID infection.  This most likely reflects the strains placed on many young people during the pandemic.”