Age-related differences in SARS-CoV-2 binding factors: An explanation for reduced susceptibility to severe COVID-19 among children?

IF 4.7 3区医学 Q1 PEDIATRICS Paediatric Respiratory Reviews Pub Date : 2022-12-01 DOI:10.1016/j.prrv.2022.01.008

Thomas Abrehart , Randy Suryadinata , Conor McCafferty , Jonathan Jacobson , Vera Ignjatovic , Phil Robinson , Nigel W. Crawford , Paul Monagle , Kanta Subbarao , Catherine Satzke , Danielle Wurzel

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引用次数: 6

Abstract

Context

In contrast with other respiratory viruses, children infected with SARS-CoV-2 are largely spared from severe COVID-19.

Objectives

To critically assess age-related differences in three host proteins involved in SARS-CoV-2 cellular entry: angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and furin.

Methods

We systematically searched Medline, Embase, and PubMed databases for relevant publications. Studies were eligible if they evaluated ACE2, TMPRSS2 or furin expression, methylation, or protein level in children.

Results

Sixteen papers were included. Age-dependent differences in membrane-bound and soluble ACE2 were shown in several studies, with ACE2 expression increasing with age. TMPRSS2 and furin are key proteases involved in SARS-CoV-2 spike protein cleavage. TMPRSS2 expression is increased by circulating androgens and is thus low in pre-pubertal children. Furin has not currently been well researched.

Limitations

High levels of study heterogeneity.

Conclusions

Low expression of key host proteins may partially explain the reduced incidence of severe COVID-19 among children, although further research is needed.

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SARS-CoV-2结合因子的年龄相关差异:儿童对严重COVID-19易感性降低的解释?

与其他呼吸道病毒相比，感染SARS-CoV-2的儿童在很大程度上幸免于严重的COVID-19。目的严格评估参与SARS-CoV-2细胞进入的三种宿主蛋白的年龄相关差异:血管紧张素转换酶2 (ACE2)、跨膜丝氨酸蛋白酶2 (TMPRSS2)和furin。方法系统检索Medline、Embase和PubMed数据库，查找相关文献。如果研究评估了ACE2、TMPRSS2或furin在儿童中的表达、甲基化或蛋白水平，则该研究是合格的。结果共纳入16篇论文。几项研究显示，膜结合和可溶性ACE2的年龄依赖性差异，ACE2的表达随着年龄的增长而增加。TMPRSS2和furin是参与SARS-CoV-2刺突蛋白切割的关键蛋白酶。TMPRSS2表达通过循环雄激素增加，因此在青春期前儿童中表达较低。呋喃目前还没有得到很好的研究。局限性:研究异质性高。结论关键宿主蛋白表达缓慢可能是儿童重症COVID-19发病率降低的部分原因，但仍需进一步研究。

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来源期刊

Paediatric Respiratory Reviews 医学-呼吸系统

CiteScore

12.50

自引率

0.00%

发文量

审稿时长

23 days

期刊介绍： Paediatric Respiratory Reviews offers authors the opportunity to submit their own editorials, educational reviews and short communications on topics relevant to paediatric respiratory medicine. These peer reviewed contributions will complement the commissioned reviews which will continue to form an integral part of the journal. Subjects covered include: • Epidemiology • Immunology and cell biology • Physiology • Occupational disorders • The role of allergens and pollutants A particular emphasis is given to the recommendation of "best practice" for primary care physicians and paediatricians. Paediatric Respiratory Reviews is aimed at general paediatricians but it should also be read by specialist paediatric physicians and nurses, respiratory physicians and general practitioners. It is a journal for those who are busy and do not have time to read systematically through literature, but who need to stay up to date in the field of paediatric respiratory and sleep medicine.