Background

Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer.

Methods

We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection.

Findings

Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm³ (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm³ (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020).

Interpretation

In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness.

Funding

American Lebanese Syrian Associated Charities and the National Cancer Institute.

中文翻译：

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SARS-CoV-2 感染儿童和青少年癌症 (GRCCC) 的全球特征和结局：一项队列研究

背景

此前的研究表明，患有 COVID-19 的儿童和青少年通常病情较轻。然而，患有癌症的儿童和青少年在感染呼吸道病毒时可能会患上严重的疾病。在这项研究中，我们旨在了解儿童和青少年癌症患者感染 SARS-CoV-2 的临床过程和结果。

方法

我们对来自 45 个国家/地区的 131 个机构的数据进行了队列研究。我们创建了儿童癌症 COVID-19 全球登记处，以收集与患有癌症或接受造血干细胞移植的儿童和青少年（<19 岁）经实验室确认的 SARS-CoV-2 感染有关的去识别化数据。没有特定于中心的排除标准。注册表通过电子邮件和会议通过专业网络传播，并邀请医疗保健提供者提交所有符合条件的案例。收集了人口统计学、肿瘤学诊断、临床病程和癌症治疗细节的数据。主要结果是疾病的严重程度和对癌症导向治疗的修改。注册表对数据收集保持开放。

发现

在 2020 年 4 月 15 日至 2021 年 2 月 1 日期间提交的 1520 起事件中，有 1500 名患者被纳入研究。1319 名患者完成了 30 天的随访。1301 名患者中有 259 名（19·9%）患有严重或危重感染，1319 名患者中有 50 名（3·8%）死于 COVID-19 感染。在接受积极肿瘤治疗的 1092 名患者中，有 609 名 (55·8%) 改变了针对癌症的治疗。多变量分析揭示了与严重或危重疾病相关的几个因素，包括世界银行低收入或中低收入（比值比 [OR] 5·8 [95% CI 3·8–8·8]；p<0· 0001) 和中高收入 (1·6 [1·2–2·2]; p=0·0024) 国家地位；15–18 岁 (1·6 [1·1–2·2]; p=0·013)；每毫米^{3 300 个或更少细胞的绝对淋巴细胞计数}(2·5 [1·8–3·4]; p<0·0001)，中性粒细胞绝对计数为每毫米³ 500 个或更少的细胞(1·8 [1·3–2·4]; p=0· 0001) 和强化治疗 (1·8 [1·3–2·3]; p=0·0005)。与治疗调整相关的因素包括中高收入国家状况 (OR 0·5 [95% CI 0·3–0·7]; p=0·0004)、其他血液恶性肿瘤的初步诊断 (0·5 [0 ·3–0·8]；p=0·0088），就诊时存在一种或多种 COVID-19 症状（1·8 [1·3–2·4]；p=0·0002） , 以及存在一种或多种合并症 (1·6 [1·1–2·3]; p=0·020)。

解释

在这个患有癌症和 COVID-19 的儿童和青少年的全球队列中，五分之一的患者发生了严重和危重疾病，并且死亡的比例高于文献中报道的普通儿科人群。此外，我们发现与治疗调整相关的变量与与疾病严重程度相关的变量不同。这些数据可以为临床实践指南提供信息，并在全球范围内提高人们对患有癌症的儿童和青少年患上严重 COVID-19 疾病的高风险的认识。

资金

美国黎巴嫩叙利亚联合慈善机构和国家癌症研究所。