Understanding the age divide in COVID-19: why are children overwhelmingly spared?
Understanding the age divide in COVID-19: why are children overwhelmingly spared?
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DOI：
10.1152/ajplung.00183.2020
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发表时间：
2020-07-01
影响因子：
4.9
通讯作者：
Harting, M. T.
中科院分区：
文献类型：
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作者：
Lingappan, K.;Karmouty-Quintana, H.;Harting, M. T.
SARS-CoV-2疾病（COVID-19）的迅速出现和随后的全球传播已导致全球400多万例病例。这种疾病明显倾向于成人，儿童相对幸免。在临床过程和实验疾病模型中，了解与疾病发生和进展相关的病理生理途径和过程的年龄差异可能是确定治疗靶点的关键。在大多数儿童中，SARS-CoV-2感染在轻度症状之外没有进展，而在成人中，疾病进展为急性肺损伤和急性呼吸窘迫综合征（ARDS）样表型，死亡率高，这突出了临床过程的差异。导致儿童肺损伤减少的病理生理机制可能涉及病毒进入呼吸道上皮所需介质的表达减少和儿童免疫系统反应的差异。具体来说，儿童气道上皮中血管紧张素转换酶2 （ACE2）和跨膜丝氨酸蛋白酶2 （TMPRSS2）等蛋白表达的降低可能会阻止病毒进入。与成人相比，免疫系统差异可能包括CD4(+) T细胞的相对优势，中性粒细胞浸润减少，促炎细胞因子的产生减少以及免疫调节细胞因子的产生增加。值得注意的是。儿童发育中的肺在病毒感染后可能有更大的恢复和修复能力。了解上述过程对发育中的肺保护性表型的相对贡献可以指导成人适当治疗的试验。
The rapid emergence and subsequent global dissemination of SARS-CoV-2 disease (COVID-19) has resulted in over 4 million cases worldwide. The disease has a marked predilection for adults, and children are relatively spared. Understanding the age-based differences in pathophysiological pathways and processes relevant to the onset and progression of disease both in the clinical course and in experimental disease models may bold the key to the identification of therapeutic targets. The differences in the clinical course are highlighted by the lack of progression of the SARS-CoV-2 infection beyond mild symptoms in a majority of children, whereas in adults the disease progresses to acute lung injury and an acute respiratory distress syndrome (ARDS)-like phenotype with high mortality. The pathophysiological mechanisms leading to decreased lung injury in children may involve the decreased expression of the mediators necessary for viral entry into the respiratory epithelium and differences in the immune system responses in children. Specifically, decreased expression of proteins, including angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in the airway epithelium in children may prevent viral entry. The immune system differences may include a relative preponderance of CD4(+) T cells, decreased neutrophil infiltration, decreased production of proinflammatory cytokines, and increased production of immunomodulatory cytokines in children compared with adults. Notably. the developing lung in children may have a greater capacity to recover and repair after viral infection. Understanding the relative contributions of the above processes to the protective phenotype in the developing lung can guide the trial of the appropriate therapies in adults.