Which children and young people are at higher risk of severe disease and death after SARS-CoV-2 infection: a systematic review and individual patient meta-analysis

Abstract

Background We aimed to use individual patient data to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in children and young people (CYP) in hospital.Methods We searched Pubmed, European PMC, Medline and Embase for case series and cohort studies that included all CYP admitted to hospital with 30 CYP with SARS-CoV-2 or 5 CYP with PIMS-TS or MIS-C. Eligible studies contained 1) details of age, sex, ethnicity or co-morbidities, and 2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted grouping of co-morbidities were eligible for narrative review. Authors of eligible studies were approached for individual patient data (IPD). We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI).Findings 81 studies were included, 57 in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years, infants had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)). Number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a dose-related fashion. For critical care admission odds ratios were: 1 comorbidity 1.49 (1.45-1.53); 2 comorbidities 2.58 (2.41-2.75); ≥3 comorbidities 2.97 (2.04-4.32), and for death: 1 comorbidity 2.15 (1.98-2.34); 2 comorbidities 4.63 (4.54-4.74); ≥3 co-morbidities 4.98 (3.78-6.65). Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities.Interpretation Hospitalised CYP at greatest vulnerability of severe disease or death from SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions.

Comorbidities in Children with COVID-19 and MIS-C/PIMS-TS and Risk Factors for Hospitalization, Severe Disease, Intensive Care and Death

“…Because of highly heterogeneous ethnicity, resources and health care systems particularly in countries with low gross domestic product this review focused predominantly on studies from European countries. American and Asian cohorts are only briefly discussed based on the review and meta-analyses from Harwood et al [14].…”

“…g. hospitalization, intensive care and death). The data has been summed up in the comprehensive review and meta-analysis by Harwood et al [14]. The American data compiled in the meta-analysis von Harwood et al includes several thousand cases.…”

“…Comorbidities, especially obesity, identified as a risk factors for a severe course in several studies. In some studies ethnicity and young age were also described as predictors for a poor outcome [14]. A large cross sectional study from the United States (which is not included in the meta-analysis from Harwood et al [14]) of 43465 patients aged 18 years or younger with COVID-19 from a hospital based database could demonstrate that more than one-quarter had one or more underlying condition.…”

“…In some studies ethnicity and young age were also described as predictors for a poor outcome [14]. A large cross sectional study from the United States (which is not included in the meta-analysis from Harwood et al [14]) of 43465 patients aged 18 years or younger with COVID-19 from a hospital based database could demonstrate that more than one-quarter had one or more underlying condition. The most common underlying conditions/comorbidities were asthma, obesity, neurodevelopment disorders and certain mental health conditions (see ▶ Table 3 for the respective comorbidities and risk ratio (95 %CI)) [16].…”

“…Association between underlying medical conditions/comorbidities and risk of hospitalization or severe illness in an US cross sectional study which included 43 465 patients with COVID-19 aged ≤ 18 years (Kompaniyets et al[16]). Association between underlying medical conditions/comorbidities and risk of admission to critical care (PICU) and death (COVID-19, MIS-C/PIMS-TS) from an individual patient meta-analysis include 22 studies with 10.022 children (data from supplement Harwood et al[14]). young children more often hospitalized, children > 5 years of age accounts for 0nly 4 % of hospital admissions).…”