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Objectives: To review the evidence of the transmissibility and severity of infection with the Delta variant of SARS-CoV-2 in children. Design: Systematic review. Data sources: PubMed, Embase, medRxiv, Web of Science, and WHO COVID database. Study selection: English language original articles, case reports, commentaries, and letters with relevant primary data, which examined evidence for the transmissibility and severity of infection with the Delta variant of SARS-CoV-2 in children. Methods: Five databases were searched for articles from the period October 2020 to March 2022. Reference lists of eligible studies and grey literature were hand searched for additional studies for inclusion. Articles that provided adequate epidemiological data including infection, transmission, or severity (including hospitalisation and death) with probable or confirmed cases of the Delta variant of SARS-CoV-2 in children (aged ≤9 years) and adolescents (aged 10 to 19 years) were included. Data were extracted for country of origin; participant characteristics (age and sex); sample size; vaccination status; and outcomes, including incidence, secondary attack rate, hospitalisation, ICU, and mortality. All included studies were assessed for bias using the Joanna Briggs Institute Critical Appraisal checklists. Results: 298 studies were found through database searching. After screening, 21 studies were included in the systematic review. Of the included studies, all were deemed to be of moderate to high quality, therefore all were included in the final analysis. Increased incidence was reported in two population studies in the USA and Australia during the period of Delta predominance. Age-related data were available for 14 studies and showed higher rates of infection in older children compared to younger children. Attack rates in educational settings were higher when an adult was the primary case. Data on severity were available from 12 studies and showed that severe disease remained rare, with increasing hospitalisation numbers in proportion to increasing paediatric cases. Vaccination was protective for severe disease, with studies in the United States, Israel and Europe showing less healthcare encounters, emergency department presentations and hospitalisations amongst vaccinated adolescents. Several studies pointed to educational and household settings as key sites for paediatric infection with the Delta variant. Conclusion: A growing proportion of COVID-19 cases were diagnosed in children during the study period due to increased transmissibility of the SARS-CoV-2 Delta variant, with an increasing number of outbreaks observed in household and educational settings likely attributed to low vaccine coverage among children. While severe disease remains uncommon, the impact of vaccination in both adults and adolescents has been shown to reduce paediatric hospitalisation rates.

Increasing integrity concerns in medical research have prompted the development of tools to detect untrustworthy studies. Existing tools primarily assess published aggregate data (AD), though scrutiny of individual participant data (IPD) is often required to detect trustworthiness issues. Thus, we developed the IPD Integrity Tool for detecting integrity issues in randomised trials with IPD available. This manuscript describes the development of this tool. We conducted a literature review to collate and map existing integrity items. These were discussed with an expert advisory group; agreed items were included in a standardised tool and automated where possible. We piloted this tool in two IPD meta-analyses (including 116 trials) and conducted preliminary validation checks on 13 datasets with and without known integrity issues. We identified 120 integrity items: 54 could be conducted using AD, 48 required IPD, and 18 were possible with AD, but more comprehensive with IPD. An initial reduced tool was developed through consensus involving 13 advisors, featuring 11 AD items across four domains, and 12 IPD items across eight domains. The tool was iteratively refined throughout piloting and validation. All studies with known integrity issues were accurately identified during validation. The final tool includes seven AD domains with 13 items and eight IPD domains with 18 items. The quality of evidence informing healthcare relies on trustworthy data. We describe the development of a tool to enable researchers, editors, and others to detect integrity issues using IPD. Detailed instructions for its application are published as a complementary manuscript in this issue.

Increasing concerns about the trustworthiness of research have prompted calls to scrutinise studies' Individual Participant Data (IPD), but guidance on how to do this was lacking. To address this, we developed the IPD Integrity Tool to screen randomised controlled trials (RCTs) for integrity issues. Development of the tool involved a literature review, consultation with an expert advisory group, piloting on two IPD meta-analyses (including 73 trials with IPD), preliminary validation on 13 datasets with and without known integrity issues, and evaluation to inform iterative refinements. The IPD Integrity Tool comprises 31 items (13 study-level, 18 IPD-specific). IPD-specific items are automated where possible, and are grouped into eight domains, including unusual data patterns, baseline characteristics, correlations, date violations, patterns of allocation, internal and external inconsistencies, and plausibility of data. Users rate each item as having either no issues, some/minor issue(s), or many/major issue(s) according to decision rules, and justification for each rating is recorded. Overall, the tool guides decision-making by determining whether a trial has no concerns, some concerns requiring further information, or major concerns warranting exclusion from evidence synthesis or publication. In our preliminary validation checks, the tool accurately identified all five studies with known integrity issues. The IPD Integrity Tool enables users to assess the integrity of RCTs via examination of IPD. The tool may be applied by evidence synthesists, editors and others to determine whether an RCT should be considered sufficiently trustworthy to contribute to the evidence base that informs policy and practice.