Department of Paediatrics, the University of Melbourne, Parkville, Australia.
Department of Respiratory Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia; Infection and Immunity, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
Paediatr Respir Rev. 2022 Dec;44:61-69. doi: 10.1016/j.prrv.2022.01.008. Epub 2022 Feb 8.
In contrast with other respiratory viruses, children infected with SARS-CoV-2 are largely spared from severe COVID-19.
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.
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.
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.
High levels of study heterogeneity.
Low expression of key host proteins may partially explain the reduced incidence of severe COVID-19 among children, although further research is needed.
与其他呼吸道病毒不同，感染 SARS-CoV-2 的儿童很少患严重的 COVID-19。
批判性评估参与 SARS-CoV-2 细胞进入的三种宿主蛋白（血管紧张素转换酶 2（ACE2）、跨膜丝氨酸蛋白酶 2（TMPRSS2）和弗林蛋白酶）的年龄相关差异。
我们系统地搜索了 Medline、Embase 和 PubMed 数据库中的相关出版物。如果研究评估了 ACE2、TMPRSS2 或弗林蛋白酶在儿童中的表达、甲基化或蛋白水平，则符合入选标准。
纳入了 16 篇论文。几项研究表明，膜结合和可溶性 ACE2 存在年龄依赖性差异，ACE2 表达随年龄增长而增加。TMPRSS2 和弗林蛋白酶是参与 SARS-CoV-2 刺突蛋白切割的关键蛋白酶。TMPRSS2 的表达受循环雄激素的上调，因此在青春期前儿童中较低。弗林蛋白酶尚未得到充分研究。
研究异质性高。
关键宿主蛋白表达水平低可能部分解释了儿童中严重 COVID-19 发病率较低的原因，但仍需要进一步研究。
