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.

中文翻译：

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哪些儿童和年轻人感染 SARS-CoV-2 后患严重疾病和死亡的风险更高：系统评价和个体患者荟萃分析

背景 我们旨在使用个体患者数据来描述与严重疾病相关的预先存在的因素，主要是入院重症监护，以及儿童和年轻人 (CYP) 住院期间继发于 SARS-CoV-2 感染的死亡。方法 我们在 Pubmed、European PMC、Medline 和 Embase 中搜索病例系列和队列研究，其中包括所有入院的 CYP ≥30 CYP 与 SARS-CoV-2 或≥5 CYP 与 PIMS-TS 或 MIS-C。符合条件的研究包含 1) 年龄、性别、种族或合并症的详细信息，以及 2) 包括进入重症监护、机械有创通气、心血管支持或死亡的结果。报告更受限制的合并症分组结果的研究有资格进行叙述性审查。就个体患者数据 (IPD) 与符合条件的研究的作者进行了接触。我们使用随机效应荟萃分析汇总研究级数据和 IPD 数据的多级混合效应模型，以检查与重症监护和死亡相关的风险因素（年龄、性别、合并症）。显示的数据是优势比和 95% 置信区间 (CI)。结果 纳入了 81 项研究，其中 57 项在荟萃分析中（其中 22 项提供 IPD）和 26 项在叙述综合中。大多数研究在其设计或报告中都存在偏倚因素。性与重症监护或死亡无关。与 1-4 岁的 CYP 相比，婴儿进入重症监护（OR 1.63 (95% CI 1.40-1.90)）和死亡（OR 2.08 (1.57-2.86)）的几率增加。CYP 10 年内的死亡几率增加（10-14 岁或 2.15 (1.54-2.98)；> 14 岁或 2.15 (1.61-2.88)）。合并症的数量与 COVID-19 进入重症监护和死亡的几率以剂量相关的方式增加。重症监护入院比值比为： 1 合并症 1.49 (1.45-1.53​​)；2 合并症 2.58 (2.41-2.75)；≥3 合并症 2.97 (2.04-4.32)，死亡 1 合并症 2.15 (1.98-2.34)；2 合并症 4.63 (4.54-4.74)；≥3 合并症 4.98 (3.78-6.65)。除了哮喘 (0.92 (0.91-0.94)) 和恶性肿瘤 (0.85 (0.17-4.21)) 之外，所有合并症的重症监护几率都增加了，除了哮喘之外，所有合并症的死亡几率都增加了。神经系统和心脏合并症与严重疾病或死亡几率的最大增加有关。肥胖增加了严重疾病和死亡的几率，而与其他合并症无关。解释 最容易因 SARS-CoV-2 感染而导致严重疾病或死亡的住院 CYP 是婴儿、青少年、患有心脏或神经系统疾病或 2 种或更多合并症的人以及肥胖者。应将这些群体视为接种疫苗和适当时进行保护性屏蔽的优先事项。虽然优势比很高，但与没有基础疾病的儿童相比，大多数合并症的风险绝对增加很小。