Developing survey weights to ensure representativeness in a national, matched cohort study: results from the Children and young people with Long Covid (CLoCk) study. (preprint)

Background: Findings from studies assessing Long Covid in children and young people (CYP) need to be viewed in light of their methodological limitations. For example, if non-response and/or attrition over time systematically differ by sub-groups of CYP, findings could be biased and generalisation limited. The present study aimed to (i) construct survey weights for the Children and young people with Long Covid (CLoCk) study, and (ii) apply them to published CLoCk findings showing the prevalence of shortness of breath and tiredness increased over time from baseline to 12-months post-baseline in both SARS-CoV-2 Positive and Negative CYP. Methods: Logistic regression was used to compute the probability of (i) Responding given envisioned to take part, (ii) Responding timely given responded, and (iii) (Re)infection given timely response. Response, timely response and (re)infection weights were generated as the reciprocal of the corresponding probability, with an overall ‘envisioned population’ survey weight derived as the product of these weights. Survey weights were trimmed, and an interactive tool developed to re-calibrate target population survey weights to the general population using data from the 2021 UK Census. Results: Flexible survey weights for the CLoCk study were successfully developed. In the illustrative example re-weighted results (when accounting for selection in response, attrition, and (re)infection) were consistent with published findings. Conclusions: Flexible survey weights to address potential bias and selection issues were created for and used in the CLoCk study. Previously reported prospective findings from CLoCk are generalisable to the wider population of CYP in England. This study highlights the importance of considering selection into a sample and attrition over time when considering generalisability of findings.

A cross-sectional study of the health of emerging young adults in England following a COVID-19 infection

Purpose This study describes long COVID symptomatology in a national sample of 18–20-year-olds with PCR-confirmed SARS-CoV-2 and matched test-negative controls in England. Symptoms in 18-20-year-olds were compared to younger adolescents (aged 11-17 years) and all adults (18+). Methods A national database was used to identify SARS-CoV-2 PCR-positive 18–20-year-olds and test-negative controls matched by time of test, age, gender and geographical region. Participants were invited to complete a questionnaire about their health retrospectively at time of test and also when completing the questionnaire. Comparison cohorts included Children and Young People with Long COVID and Real-time Assessment of Community Transmission studies. Results Of 14,986 people invited, 1,001 were included in the analysis (562 test-positive;440 test-negative). At testing, 46.5% of test-positives and 16.4% of test-negatives reported at least one symptom. At the time of questionnaire completion (median 7 months post-testing), 61.5% of test-positives and 47.5% of test-negatives reported one or more symptoms. The most common symptoms were similar amongst test-positives and test-negatives and included tiredness (44.0%;35.7%), shortness of breath (28.8%;16.3%) and headaches (13.7%;12.0%). Prevalence rates were similar to those reported by 11-17-year-olds (66.5%) and higher than those reported in all adults (37.7%). For 18-20-year-olds, there was no significant difference in health-related quality of life and wellbeing (p>0.05). However, test-positives reported being significantly more tired than test-negatives (p=0.04). Conclusions Seven months after PCR test, a high proportion of test-positive and test-negative 18-20-year-olds reported similar symptoms to each other and to those experienced by younger and older counterparts.

Developing a model for predicting impairing physical symptoms in children 3 months after a SARS-CoV-2 PCR-test: The CLoCk Study (preprint)

Abstract Importance: Predictive models can help identify SARS-CoV-2 patients at greatest risk of post-COVID sequelae and direct them towards appropriate care. Objective: To develop and internally validate a model to predict children and young people most likely to experience at least one impairing physical symptom 3 months after a SARS-CoV-2 PCR-test and to determine whether the impact of these predictors differed by SARS-CoV-2 infection status. Design: Potential pre-specified predictors included: SARS-CoV-2 status, sex, age, ethnicity, deprivation, quality of life/functioning (5 EQ-5D-Y items), physical and mental health, and loneliness (all prior to SARS-CoV-2 testing), and number of physical symptoms at testing. Logistic regression was used to develop the model. Model performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping; the final model was adjusted for overfitting. Setting: National cohort study of SARS-CoV-2 PCR-positive and PCR-negative participants matched according to age, sex, and geographical area. Participants: Children and young people aged 11-17 years who were tested for SARS-CoV-2 infection in England, January to March 2021. Main outcome measure: one or more physical symptom 3 months after initial PCR-testing which affected physical, mental or social well-being and interfered with daily living. Results: A total of 50,836 children and young people were approached; 7,096 (3,227 test-positives, 3,869 test-negatives) who completed a questionnaire 3 months after their PCR-test were included. 39.6% (1,279/3,227) of SAR-CoV-2 PCR-positives and 30.6% (1,184/3,869) of SAR-CoV-2 PCR-negatives had at least one impairing physical symptom 3 months post-test. The final model contained predictors: SARS-COV-2 status, number of symptoms at testing, sex, age, ethnicity, self-rated physical and mental health, feelings of loneliness and four EQ-5D-Y items before testing. Internal validation showed minimal overfitting with excellent calibration and discrimination measures (optimism adjusted calibration slope:0.97527; C-statistic:0.83640). Conclusions and relevance: We developed a risk prediction equation to identify those most at risk of experiencing at least one impairing physical symptom 3 months after a SARS-CoV-2 PCR-test which could serve as a useful triage and management tool for children and young people during the ongoing pandemic. External validation is required before large-scale implementation.

Persistent Symptoms Following SARS-CoV-2 Infection Among Children and Young People: A Meta-Analysis of Controlled and Uncontrolled Studies (preprint)

Background: Data on the long-term impact of SARS-CoV-2 infection in children and young people (CYP) is conflicting. We assessed evidence on long-term post-COVID symptoms in CYP examining prevalence, risk factors, type and duration.Methods: Systematic search of published and unpublished literature using 13 online databases between 01/12/2019 – 31/07/2021. Eligible studies reported CYP ≤19 years with confirmed or probable SARS-CoV-2 with any symptoms persisting beyond acute illness. Random effects meta-analyses examined pooled risk difference in symptom prevalence (controlled studies only) and pooled prevalence (uncontrolled studies also included). Meta-regression examined study characteristics hypothesised to be associated with symptom prevalence. Prospectively registered: CRD42021233153. Findings: Twenty two of 3357 unique studies were eligible, including 23,141 CYP. Median duration of follow-up was 125 days (IQR 99-231).Pooled risk difference in post-COVID cases compared to controls (5 studies) were significantly higher for cognitive difficulties (3% (95% CI 1, 4)), headache (5% (1, 8)), loss of smell (8%, (2, 15)), sore throat (2% (1, 2)) and sore eyes (2% (1, 3)) but not abdominal pain, cough, fatigue, myalgia, insomnia, diarrhoea, fever, dizziness or dyspnoea.Pooled prevalence of symptoms in post-COVID participants in 17 studies ranged from 15% (diarrhoea) to 47% (fatigue). Age was associated with higher prevalence of all symptoms except cough. Higher study quality was associated with lower prevalence of all symptoms, except loss of smell and cognitive symptoms.Interpretation: The frequency of the majority of reported persistent symptoms was similar in SARS-CoV-2 positive cases and controls. This systematic review and meta-analysis highlights the critical importance of a control group in studies on CYP post SARS-CoV-2 infection.Funding: None to declare. Declaration of Interest: SAB, RS, SDB, AXDZ, LLO, SNL, BLDS, RMV and OVS have no conflicts of interest. TJS is the Chair of the Health Research Authority for England who reimburse his university for his time. He is not paid personally. He has recused himself from research studies in which he is personally involved and which require ethical approval from the HRA.