Long-Term Effects of COVID-19 in Children and Young People: A 24-Month National Cohort Study
Authors: Pereira Snehal Pinto , Stephenson Terence , Nugawela Manjula , Dalrymple Emma , Harnden Anthony , Whittaker Elizabeth , Heyman Isobel , Ford Tamsin , Segal Terry , Chalder Trudie , Ladhani Shamez , McOwat Kelsey , Simmons Ruth , Xu Laila , Fox-Smith Lana , Consortium CLoCk , Shafran Roz 
Published: December 2023

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.
Funding
This work is independent research jointly funded by The Department of Health and Social Care, in their capacity as the National Institute for Health Research (NIHR), and by UK Re-search & Innovation (UKRI) who have awarded funding grant number COV-LT-0022. The Department of Health and Social Care, as the NIHR, and UKRI were not involved in study design, data collection, analysis or interpretation of the data, nor the writing of the present study or the decision to submit the article for publication. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, UKRI or the Department of Health. SMPP is supported by a UK Medical Research Council Career Development Award (ref: MR/P020372/1).
Copyright
For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.