Prognostic factors for mortality, ICU, MIS-C and hospital admission due to SARS-CoV-2 in paediatric patients: A systematic review and meta-analysis

ABSTRACT Background: There is a paucity of data on the factors associated with severe COVID-19 disease, especially in children. This systematic review and meta-analysis aim to identify the risk factors for acute adverse outcomes of COVID-19 within paediatric populations, using the recruitment setting as a proxy of initial disease severity. Methods: A systematic review and meta-analysis were performed representing published evidence from the start of the pandemic up to 14 February 2022. Our primary outcome was the identification of risk factors for adverse outcomes, stratified by recruitment setting (community, hospital). No geographical restrictions were imposed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty in the body of evidence for each meta-analysis. In anticipation of significant clinical and methodological heterogeneity in the meta-analyses, we fitted logistic regression models with random effects. Findings: Our review identified 47 studies involving 94,210 paediatric cases of COVID-19. Infants up to 3 months were more likely to be hospitalised than older children. Gender and ethnicity were not associated with an increased likelihood of adverse outcomes among children within the community setting. Concerning comorbidities, having at least one pre-existing disease increased the odds of hospitalisation. Concerning BMI, underweight children and severely obese were noted to have an increased likelihood of hospital admission. The presence of metabolic disorders and children with underlying cardiovascular diseases, respiratory disorders, neuromuscular disorders and neurologic conditions were also more likely to be hospitalised. Concerning underlying comorbidities, paediatric hospitalised patients with congenital/genetic disease, those obese, with malignancy, cardiovascular diseases and respiratory disease were associated with higher odds of being admitted to ICU or ventilated. Interpretation: Our findings suggest that age, male, gender, and paediatric comorbidities increased the likelihood of hospital and ICU admission. Obesity, malignancy, and respiratory and cardiovascular disorders were among the most important risk factors for hospital and ICU admission among children with COVID-19. The extent to which these factors were linked to actual severity or where the application of cautious preventive care is an area in which further research is needed. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement European Centre for Disease Prevention and Control (ECDC) under specific contract No. 19 ECD.12254 within Framework contract ECDC/2019/001 Lot 1B. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript