Background

Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood.

Data sources

A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included “COVID-19 in children”, “severe pediatric COVID-19”, and “critical illness in children with COVID-19”.

Results

Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines.

Conclusions

Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

中文翻译：

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重症儿科 COVID-19：临床和免疫病理生理学角度的综述

背景

2019 年冠状病毒病 (COVID-19) 在儿童中往往表现较轻。然而，严重和危重病例确实在儿科人群中出现，具有使系统性衰弱的影响，有时甚至可能致命，值得临床医生进一步关注。与此同时，病原体毒力因子和宿主防御机制之间错综复杂的相互作用被认为在严重的 COVID-19 病理生理学中发挥着不可或缺的作用，但仍不完全清楚。

数据源

审稿人独立使用 PubMed、Embase 和万方数据库对相关出版物进行了全面的文献综述。搜索的关键词包括“儿童COVID-19”、“重症儿科COVID-19”和“患有COVID-19的儿童危重疾病”。

结果

随着合并症数量的增加和未接种疫苗的情况的增加，儿童患严重 COVID-19 的风险也会随之增加。急性呼吸窘迫应激和坏死性肺炎是突出的肺部表现，同时也可见各种形式的心血管和神经系统受累。宿主对 COVID-19 的反应涉及多种免疫过程，包括 I 型干扰素和炎症小体途径，其在严重和危重疾病中的失调会转化为不良的临床表现。儿童多系统炎症综合征 (MIS-C) 是一种可能危及生命的免疫介导疾病，按时间顺序与 COVID-19 暴露相关，它是另一个科学和临床难题，体现了儿科免疫的复杂性。尽管儿童和成人免疫系统之间存在相当大的差异，但缺乏专门针对儿童的临床试验，并且当前的管理建议很大程度上改编自成人指南。

结论

严重的儿科 COVID-19 可能会影响多个器官系统。严重 COVID-19 中免疫途径失调决定了疾病进程，体现了儿科免疫系统的巨大功能多样性，并突出了儿童和成人之间的免疫表型差异。因此，可能需要进一步的研究，以在儿科特定的临床实践指南中充分解决这些问题。