Preprint Long-Term Effects of COVID-19 in Children and Young People: A 24-Month National Cohort Study, 2023, Pereira

[Dolphin]

https://www.researchsquare.com/article/rs-3750111/v1

Long-Term Effects of COVID-19 in Children and Young People: A 24-Month National Cohort Study

Snehal Pinto Pereira1

Terence Stephenson

Manjula Nugawela

Emma Dalrymple

Anthony Harnden

Elizabeth Whittaker

Isobel Heyman

Tamsin Ford2

Terry Segal

Trudie Chalder

Shamez Ladhani

Kelsey McOwat

Ruth Simmons

Laila Xu

Lana Fox-Smith

ORCID

CLoCk Consortium

Roz Shafran

1 University College London,

2 University Cambridge

https://doi.org/10.21203/rs.3.rs-3750111/v1

This work is licensed under a CC BY 4.0 License

Background

Most children and young people (CYP) in the United Kingdom have been infected with SARS-COV-2 and some continue to experience impairing symptoms after infection. Using data from a national cohort study, we report on symptoms and their impact 24 months post-infection for the first time.

Methods

The CloCk study is a national cohort in England, of CYP aged 11-to-17-years when they had a SARS-CoV-2 PCR test between September 2020 and March 2021. Of 31,012 CYP invited to complete a questionnaire 24-months post-PCR test, 12,632 CYP participated and were included in our analytic sample (response rate=40·7%). CYP were divided into four groups depending on their infection status: ‘initial test-negatives with no subsequent positive test’ (NN); ‘initial test-negatives with a subsequent positive test’ (NP); ‘initial test-positives with no report of subsequent re-infection’ (PN); and ‘initial test-positives with report of subsequent re-infection’ (PP). We examined whether symptom profiles 24-months post index-test differed by infection status using chi-squared or Mann-Whitney tests.

Findings

7.2% of CYP consistently fulfilled the definition of PCC at 3-, 6-, 12- and 24-months. These young people had a median of 5 or 6 symptoms at each time point. Between 20-25% of all four infection status groups reported 3 or more symptoms 24 months after testing and 10-25% of CYP experienced 5+ symptoms, with the reinfected (PP) group having more symptoms than the other two positive groups (NP and PN); the NN group had the lowest symptom burden (p<0.001). Symptoms or their impact did not vary by vaccination status.

PCC was more common in older (vs. younger) CYP and in the most (vs. least) deprived quintile. PCC was almost twice as common in females (vs. males) in both infection status groups.

Interpretation

The discrepancy in the proportion of CYP who fulfilled the Delphi consensus PCC definition at 24 months and those who consistently fulfilled the definition across time with multiple symptoms, highlights the importance of longitudinal studies and the need to consider clinical impairment and range of symptoms. Relatedly, further studies are needed to understand the pathophysiology, develop diagnostic tests and identify effective interventions for young people who continue to be significantly impaired by PCC.

https://twitter.com/user/status/1740187812501266797

 

[Trish]

Counting the number of symptoms seems to me a daft way of assessing disease existence and severity. What about severity of each symptom and impairment of function?

 

[Amw66]

Counting the number of symptoms seems to me a daft way of assessing disease existence and severity. What about severity of each symptom and impairment of function?

Is there a questionnaire for that ? ( Sarcasm)

 

[Jonathan Edwards]

The abstract does even remember to tell us what PCC is.
It doesn't appear to tell us anything useful.

 

[Amw66]

£££s for something an undergraduate could have come up with ?

Interesting to see how long COVID kids respond .
They have been vocal previously on aspects of this study

 

[rvallee]

The first paper from this group basically concluded "Long Covid? Doesn't appear to exist". It was a terrible paper. This is also a terrible paper, it's lazy and uninterested. It features prominent deniers of Long Covid and chronic illness in general, and they sure did a poor job of even defining it properly.

But it's part of the millions wasted by the MRC on bad Long Covid research, and to them that's a job well done because results don't matter.

 

[Amw66]

The first paper from this group basically concluded "Long Covid? Doesn't appear to exist". It was a terrible paper. This is also a terrible paper, it's lazy and uninterested. It features prominent deniers of Long Covid and chronic illness in general, and they sure did a poor job of even defining it properly.

But it's part of the millions wasted by the MRC on bad Long Covid research, and to them that's a job well done because results don't matter.

Cue a strategically placed billboard ?

 

[dave30th]

The discrepancy in the proportion of CYP who fulfilled the Delphi consensus PCC definition at 24 months and those who consistently fulfilled the definition across time with multiple symptoms, highlights the importance of longitudinal studies and the need to consider clinical impairment and range of symptoms.

I haven't read the paper. Can someone translate the first part of this sentence for me? I don't understand what they're saying.

 

[SNT Gatchaman]

I think it's commenting on the evidence that LC (frequently?) doesn't simply continue uninterrupted from acute Covid. Instead patients recover to full health, possibly having been acutely asymptomatic and then progress to LC after weeks or months. Also that the symptoms that form LC (eg. fatigue/PEM/neuro-cognitive/gut/cardiovascular) are not those that feature in the acute infection.

 

[SNT Gatchaman]

An important difference between the WHO and Delphi consensus research definition is that the WHO definition requires symptoms of PCC to have arisen within three months of the initial infection. This means that new symptoms arising 6- or 12-months post-infection should not be considered as PCC. In our data, including only participants that completed questionnaires at every possible time point from 3-months post-index test, only 7% of CYP fulfilled the definition of PCC at 3-, 6-, 12- and 24-months.

Ie some declared at 6 months (or later).

It has been argued that, partly due to lack of testing, it is likely that current estimates are underestimating the true burden of those with PCC. Moreover, cross-sectional studies provide only a static prevalence of symptoms of PCC and as these are likely to vary over time, such studies may underestimate the true burden of PCC within populations. That is why we have published CLoCk data as both ‘snap shots’ of the whole study cohort and longitudinal reports on smaller sub-sets with data at multiple timepoints. These latter analyses show that in CYP, the prevalence of adverse symptoms reported at the time of a positive PCR-test declined over the first 12-months but some test-positives and test-negatives reported adverse symptoms for the first time at six- and 12 months post-test, particularly tiredness, shortness of breath, poor quality of life, poor well-being and fatigue.

That some CYP will go on the develop persistent symptoms after acute SARS-CoV-2 infection is undeniable, consistent with other post-viral syndromes, and there is emerging evidence of viral persistence in children and immunological biomarkers in adults. It is, however, unlikely SARS-CoV-2 infection is responsible for all reported symptoms in 54-65% of CYP in our cohort.