Table_2_The Dynamic Expression of Potential Mediators of Severe Acute Respiratory Syndrome Coronavirus 2 Cellular Entry in Fetal, Neonatal, and Adult Rhesus Monkeys.XLSX

The coronavirus disease 2019 (COVID-19) pandemic, induced by the pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly all over the world. There is considerable variability among neonates, children, and adults in the incidence of infection and severe disease following exposure to SARS-CoV-2. In our study, we analyzed the transcriptome data of primate animal model of Rhesus monkeys to evaluate the expression levels of possible SARS-CoV-2 receptors and proteases and immunologic features in the lungs, colons, livers, and brains at different developmental stages. Our results revealed that ACE2 and TMPRSS2 were highly expressed in neonates compared with other populations, which imply the high incidence of infection. Other potential receptors and Type II transmembrane serine proteases (TTSPs) and cathepsin of endosomal proteases also exhibited dynamic and differential expression patterns. The expression of receptors (ACE2, BSG, and DPP4) and proteases (TMPRSS2, TMPRSS9, CTSL, and CTSB) were highly correlated during lung development, suggesting the high susceptibility of the lungs. TMPRSS9 was specifically highly expressed in the lungs and reached the highest level in neonates, similar to TMPRSS2. Moreover, the immune cell infiltration analysis revealed immunity immaturity in neonates, implying the association with the mild or moderate type of COVID-19. The results might help researchers design protective and therapeutic strategies for COVID-19 in populations at different ages.

由致病性严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2, SARS-CoV-2）引发的2019冠状病毒病（coronavirus disease 2019, COVID-19）大流行已在全球快速蔓延。暴露于SARS-CoV-2后，新生儿、儿童与成人在感染发生率及重症疾病表现上存在显著差异。本研究针对恒河猴（Rhesus monkeys）这一灵长类动物模型的转录组数据展开分析，以评估不同发育阶段恒河猴肺、结肠、肝脏及脑组织中潜在SARS-CoV-2受体、蛋白酶的表达水平与免疫学特征。研究结果显示，相较于其他人群，ACE2与TMPRSS2在新生儿体内呈高表达，提示新生儿感染风险较高。其他潜在受体、II型跨膜丝氨酸蛋白酶（Type II transmembrane serine proteases, TTSPs）以及内体蛋白酶类组织蛋白酶（cathepsin）亦呈现出动态且差异化的表达模式。在肺发育进程中，受体（ACE2、BSG与DPP4）与蛋白酶（TMPRSS2、TMPRSS9、CTSL及CTSB）的表达呈高度相关性，提示肺部具有较高的病毒易感性。TMPRSS9与TMPRSS2类似，特异性高表达于肺部，并在新生儿体内达到表达峰值。此外，免疫细胞浸润分析结果表明新生儿免疫系统尚未成熟，这暗示其与COVID-19轻症或中症病例存在关联。本研究结果可为不同年龄人群的COVID-19防护与治疗策略设计提供参考依据。