Saheb Sharif-Askari Narjes, Saheb Sharif-Askari Fatemeh, Hafezi Shirin, Kalaji Zaina, Temsah Mohamed, Almuhsen Saleh, Alsafar Habiba S, Hamid Qutayba, Halwani Rabih
Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Heliyon. 2022 Nov 17;8(11):e11724. doi: 10.1016/j.heliyon.2022.e11724. eCollection 2022 Nov.
There is emerging evidence that age-dependent differences in susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlate with stronger innate immune response in the upper respiratory tract in children compared to adults. The efficient induction of interferon (IFN) alpha and beta (α and β) signaling, and interferon-stimulated genes (ISGs) is fundamental to the host antiviral response. In-silico transcriptomic analyses was conducted to determine the expression levels of IFN α/β pathway genes as well as 524 human ISGs in upper and lower airways of children and adults at baseline and post respiratory infections including coronavirus disease 2019 (COVID-19). To validate our in-silico analysis, we conducted qRT-PCR to measure ISGs levels in children and adult's nasal epithelial samples. At baseline, children had significantly higher levels of IFN α/β and ISGs genes compared to adults. More distinction was also seen in bronchial compared to nasal basal levels. Children nasal epithelial cells exhibited superior antiviral IFN α/β and associated ISGs response following ex-vivo poly (I:C) treatment model, and in clinical samples of SARS-CoV-2 infected patients. This was also confirmed in nasal epithelial samples using qRT-PCR validation. No gender-based difference in type I IFN levels across both age groups were observed. Understanding the biological basis for children resistance against severe COVID-19 is a challenge that has substantial clinical importance. More mechanistic studies are needed to carefully quantify how much of early IFN levels is needed to bypass the viral evasion mechanism and prevent its further replication and dissemination to lower airways and the rest of the body.
越来越多的证据表明，与成人相比，儿童对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）易感性的年龄依赖性差异与上呼吸道更强的先天免疫反应相关。干扰素（IFN）α和β（α和β）信号以及干扰素刺激基因（ISG）的有效诱导是宿主抗病毒反应的基础。进行了计算机转录组分析，以确定基线时以及包括2019冠状病毒病（COVID-19）在内的呼吸道感染后，儿童和成人上、下呼吸道中IFNα/β途径基因以及524个人类ISG的表达水平。为了验证我们的计算机分析，我们进行了qRT-PCR以测量儿童和成人鼻上皮样本中的ISG水平。在基线时，与成人相比，儿童的IFNα/β和ISG基因水平显著更高。与鼻基底水平相比，支气管中的差异也更明显。在体外聚（I:C）处理模型以及SARS-CoV-2感染患者的临床样本中，儿童鼻上皮细胞表现出卓越的抗病毒IFNα/β和相关ISG反应。使用qRT-PCR验证在鼻上皮样本中也证实了这一点。在两个年龄组中均未观察到基于性别的I型干扰素水平差异。了解儿童对严重COVID-19具有抵抗力的生物学基础是一项具有重大临床意义的挑战。需要更多的机制研究来仔细量化需要多少早期干扰素水平才能绕过病毒逃避机制并防止其进一步复制和传播到下呼吸道及身体其他部位。
