Long-Term Outcomes of COVID-19 Infection in Children and Young People: A Systematic Review and Meta-Analysis

Background: Children and young people (CYP) may experience prolonged symptoms following COVID-19, commonly termed ‘Long-COVID’. The nature of this in CYP is unclear, as are the sequalae of acute COVID-19. We aimed to systematically synthesise evidence of the long-term outcomes of COVID-19 in CYP. Methods: 13 databases were searched until January 2022. Inclusion criteria: Observational studies reporting outcomes occurring four-weeks or more after COVID-19 in children <18 years old. Exclusion criteria: Outcomes of Paediatric Inflammatory Multisystem Syndrome. Title, abstract and full text screening were conducted independently by two reviewers. Data extraction and risk of bias assessment was by one reviewer with independent verification. Critical appraisal tools appropriate for study type were employed. Results were narratively synthesised with meta-analysis to generate summary estimates of risk of prolonged symptoms in CYP. Findings: 94 studies were included. 66 recruited from hospital settings, 8 recruited solely from community settings. >100 symptoms were reported, the most common being fatigue, headache and cognitive symptoms. Summary estimates of risk of prolonged symptoms were higher for hospital samples (31.2%, 95% CI 20.3% to 43.2%) than for community samples (4.6%, 95% CI 3.4% to 5.8). Sequalae including stroke, type-1 diabetes, Guillan-Barre syndrome, and persistent radiological or blood test abnormalities have been reported in CYP following COVID-19. Most studies reporting these are case reports / case series and quality of evidence is low. Interpretation: Prolonged symptoms following COVID-19 in children are variable and multi-system. Rates in community samples are lower than hospital. There is limited data on other sequalae in CYP. Heterogeneity in diagnosis of COVID-19, symptom classification, assessment method and duration of follow-up made synthesis less secure. Funding: HT, CB and GS have National Institute for Health and Care Research fellowships. RB, CM and VW are supported by the NIHR West Midlands Applied Research Collaboration. CM Is supported by the NIHR School for Primary Care Research. Declaration of Interest: We declare no competing interests.