Risk Factors for Severe COVID-19 in Children: A Systematic Review and Meta-Analysis

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been the most important global issue since December 2019. Although the clinical course of COVID-19 is known to be milder in children than in adults, associated hospitalizations among children have increased since the emergence of contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the achievement of a high vaccination rate in adults. Considering these global and domestic situations, we believe that risk stratification in children with COVID-19 is urgently needed for decision making regarding hospitalization priority in children infected with SARS-CoV-2 and vaccination priority against COVID-19. METHODS: This systematic review and meta-analysis was performed by comprehensively searching the PubMed, EMBASE, Scopus and KoreaMed databases through August 25, 2021. The criteria for enrollment were "severe COVID-19" as poor outcomes (intensive care unit admission, invasive mechanical ventilation, and/or death) and underlying comorbidities before SARS-CoV-2 infection. RESULTS: Among 872 screened studies, 17 articles were included in the systematic review, and 10 articles were included in the meta-analysis. Neonate (risk ratio [RR], 2.69; 95% confidence interval [CI], 1.83-3.97), prematurity in young infants (RR, 2.00; 95% CI, 1.63-2.46), obesity (RR, 1.43; 95% CI, 1.24-1.64), diabetes (RR, 2.26; 95% CI, 1.95-2.62), chronic lung disease (RR, 2.62; 95% CI, 1.71-4.00), heart disease (RR, 1.82; 95% CI, 1.58-2.09), neurologic disease (RR, 1.18; 95% CI, 1.05-1.33), and immunocompromised status (RR, 1.44; 95% CI, 1.01-2.04) were significant risk factors for severe COVID-19 in children. In the subgroup analysis, age younger than 3 months (RR, 0.26; 95% CI, 0.11-0.66), asthma (RR, 1.08; 95% CI, 0.98-1.20), and neurodevelopmental disorders (RR, 0.88; 95% CI, 0.75-1.04) were not risk factors for severe COVID-19. CONCLUSION: Children with comorbidities such as obesity, diabetes, heart disease, chronic lung diseases other than asthma, seizure disorders, and an immunocompromised status had a high prevalence of severe COVID-19. Neonate and premature infants had a high risk of severe COVID-19. Defining the high-risk group for severe COVID-19 could help to guide hospital admission and priority for vaccination against SARS-CoV-2.