Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cytokine. 2024 Mar;175:156495. doi: 10.1016/j.cyto.2023.156495. Epub 2024 Jan 7.
Individuals with Coronavirus Disease 2019 (COVID-19) may show no symptoms to moderate or severe complications. This variation may be due to differences in the strength of the immune response, including a delayed interferon (IFN) response in asymptomatic patients and higher IFN levels in severe patients. Some long non-coding RNAs (lncRNAs), as regulators of the IFN pathway, may contribute to the emergence of different COVID-19 symptoms. This study aimed to comparatively investigate the relationship between lncRNAs (eosinophil granule ontogeny transcript (EGOT), negative regulator of antiviral response (NRAV), and negative regulator of interferon response (NRIR)), alongside interferon-stimulated genes (ISGs) like ISG-15 and interferon-induced transmembrane protein 3 (IFITM3) in COVID-19 patients with asymptomatic, moderate, and severe symptoms. Buffy coat samples were collected from 17 asymptomatic, 23 moderate, 22 severe patients, and 44 healthy controls. Quantitative real-time PCR was utilized to determine the expression levels. In a comparison between COVID-19 patients and healthy individuals, higher expression levels of EGOT and NRAV were observed in severe and moderate patients. NRIR expression was increased across all patient groups. Meanwhile, ISG15 expression decreased in all patient groups, and the moderate group showed a significant decrease in IFITM3 expression. Comparing COVID-19 patient groups, EGOT expression was significantly higher in moderate COVID-19 patients compared to asymptomatic patients. NRAV was higher in moderate and severe patients compared to asymptomatic. NRIR levels did not differ significantly between the COVID-19 patient groups. ISG15 was higher in moderate and severe patients compared to asymptomatic. IFITM3 expression was significantly higher in severe patients compared to the moderate group. In severe COVID-19 patients, EGOT expression was positively correlated with NRAV levels. EGOT and NRAV showed a significant positive correlation in asymptomatic patients, and both were positively correlated with IFITM3 expression. This study suggests that EGOT, NRAV, NRIR, ISG15, and IFITM3 may serve as diagnostic biomarkers for COVID-19. The lncRNA NRAV may be a good biomarker in a prognostic panel between asymptomatic and severe patients in combination with other high-sensitivity biomarkers. EGOT, NRAV, and ISG15 could also be considered as specific biomarkers in a prognostic panel comparing asymptomatic and moderate patients with other high-sensitivity biomarkers.
个体感染 2019 年冠状病毒病(COVID-19)后可能表现为无症状或出现中度至重度并发症。这种差异可能是由于免疫反应强度的不同,包括无症状患者中干扰素(IFN)反应延迟以及重症患者中 IFN 水平升高所致。一些长链非编码 RNA(lncRNA),作为 IFN 通路的调节剂,可能导致不同 COVID-19 症状的出现。本研究旨在比较分析无症状、中度和重度 COVID-19 患者的 lncRNA(嗜酸性粒细胞颗粒发生转录物(EGOT)、抗病毒反应负调节剂(NRAV)和 IFN 反应负调节剂(NRIR))与干扰素刺激基因(ISG)(如 ISG-15 和干扰素诱导跨膜蛋白 3(IFITM3))之间的关系。从 17 名无症状、23 名中度、22 名重度患者和 44 名健康对照者中采集 Buffy 涂层样本。利用定量实时 PCR 检测其表达水平。在 COVID-19 患者与健康个体的比较中,重度和中度患者的 EGOT 和 NRAV 表达水平升高。所有患者组的 NRIR 表达均增加。同时,所有患者组的 ISG15 表达均降低,中度组的 IFITM3 表达显著降低。在 COVID-19 患者组之间的比较中,中度 COVID-19 患者的 EGOT 表达明显高于无症状患者。中度和重度患者的 NRAV 高于无症状患者。COVID-19 患者组之间的 NRIR 水平无显著差异。中度和重度患者的 ISG15 表达高于无症状患者。严重 COVID-19 患者的 IFITM3 表达明显高于中度患者。在重度 COVID-19 患者中,EGOT 表达与 NRAV 水平呈正相关。无症状患者中 EGOT 和 NRAV 呈显著正相关,两者均与 IFITM3 表达呈正相关。本研究表明,EGOT、NRAV、NRIR、ISG15 和 IFITM3 可用作 COVID-19 的诊断生物标志物。lncRNA NRAV 可能是无症状和重症患者预后面板中的一个良好生物标志物,与其他高灵敏度生物标志物联合使用。EGOT、NRAV 和 ISG15 也可作为无症状和中度患者预后面板中的特异性生物标志物,与其他高灵敏度生物标志物联合使用。