The Impact of Immunocompromise on Outcomes of COVID-19 in Children and Young People - A Systematic Review and Meta-Analysis

Background: Despite children and young people (CYP) having a low risk for severe Coronavirus disease 2019 (COVID-19) outcomes, there is still a degree of uncertainty related to their risk in the context of immunodeficiency or immunosuppression, primarily due to significant reporting bias in most studies, as CYP characteristically experience milder or asymptomatic COVID-19 infection and the severe outcomes tend to be overestimated. Methods: A comprehensive systematic review to identify globally relevant studies in immunosuppressed CYP and CYP in general population (defined as younger than 25 years of age) up to 31st October 2021 (to exclude vaccinated populations), was performed. Studies were included if they reported the two primary outcomes of our study, admission to intensive therapy unit (ITU) and mortality, while data on other outcomes, such as hospitalisation and need for mechanical ventilation were also collected. A meta-analysis estimated the pooled proportion for each severe COVID-19 outcome, using the inverse variance method. Random effects models were used to account for interstudy heterogeneity. Findings: The systematic review identified 30 eligible studies for each of the two populations investigated: immunosuppressed CYP (n=793) and CYP in general population (n=102,022). Our meta-analysis found higher estimated prevalence for hospitalization (46% vs. 16%), ITU admission (12% vs. 2%), mechanical ventilation (8% vs. 1%) and increased mortality due to severe COVID-19 infection (6.5% vs. 0.2%) in immunocompromised CYP compared to CYP in general population. This shows an overall trend for more severe outcomes of COVID-19 infection in immunocompromised CYP, similar to adult studies.Interpretation: This is the only up to date meta-analysis in immunocompromised CYP with high global relevance, which excluded reports from hospitalised cohorts alone and included 35% studies from low- and medium-income countries. Future research is required to characterise individual subgroups of immunocompromised patients, as well as impact of vaccination on severe COVID-19 outcomes.Funding: There was no funding source specifically dedicated for this study. CC is supported by a National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) at University College London Hospital (UCLH). The study was performed within the Centre for Adolescent Rheumatology Versus Arthritis at University College London (UCL), UCL Hospital and Great Ormond Street Hospital (GOSH) supported by grants from Versus Arthritis (21593 and 20164), Great Ormond Street Children’s Charity, and the NIHR-BRC at both GOSH and UCLH.Declaration of Interests: None.