Epidemiology and clinical features of SARS-CoV-2 infection in children and adolescents in the pre-Omicron era: A global systematic review and meta-analysis

Background: Data on paediatric SARS-CoV-2 infections are limited, especially from the early pandemic period. In addition, children are not considered to be at high risk for severe outcomes of COVID-19. This systematic review with meta-analysis estimated the SAR-CoV-2 positivity rate, identified risk factors, and described the severity and mortality outcomes of SARS-CoV-2 infections in children aged <= 18 years, until December 2021, prior to the Omicron era.<br /> Methods: We searched MEDLINE, Embase, Global Health, CINAHL, China National Knowledge Infrastructure, Wanfang, CQvip, and WHO COVID-19 global literature databases for primary studies recruiting children aged <= 18 years with a confirmed diagnosis of SARS-CoV-2 infection either by molecular or antigen tests. The Joanna Briggs Institute critical appraisal tools were used to appraise the study quality. Meta-analyses using the random effects model were conducted for all outcomes except for race/ ethnicity as risk factor of SARS-CoV-2 infection.<br /> Findings: This review included 237 studies, each reporting at least one of the study outcomes. Based on data from 117 studies, the pooled SARS-CoV-2 positivity rate was 9<middle dot>3% (95% CI = 7<middle dot>15% to 11<middle dot>73%). Having a comorbidity was identified as a risk factor for SARS-CoV-2 infection (RR = 1<middle dot>33; 95% CI = 1<middle dot>04 to 1<middle dot>71) based on data from 49 studies. Most cases in this review presented with mild disease (n = 50) [52.47% (95% CI = 44.03% to 60.84%)]. However, around 20.70% of paediatric SARS-CoV-2 infections were hospitalised (n = 67), and 7<middle dot>19%, 4<middle dot>26%, and 2<middle dot>92% required oxygen support (n = 57), intensive care (n = 93), and assisted ventilation (n = 63), respectively. The case fatality ratio (n = 119) was 0<middle dot>87% (95% CI = 0<middle dot>54% to 1<middle dot>28%).<br /> Interpretation: Although there was substantial heterogeneity across individual study estimates, our analyses showed that children were at-risk for SARS-CoV-2 infections and severe outcomes in the pre-Omicron era. These findings underscore the need for effective vaccination strategies for paediatric population to protect against the acute and long-term sequalae of COVID-19.