Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2022 Jan;72(1):27-36. doi: 10.1007/s12031-021-01941-4. Epub 2021 Dec 2.
The pandemic caused by severe acute respiratory syndrome coronavirus 2 and the related disorder i.e. "coronavirus disease 2019" (COVID-19) has encouraged researchers to unravel the molecular mechanism of disease severity. Several lines of evidence support the impact of "cytokine storm" in the pathogenesis of severe forms of the disorder. We aimed to assess expression levels of nine cytokine coding genes in COVID-19 patients admitted in a hospital. We collected clinical data of patients from their medical reports. Then, we assessed expression of genes using real-time PCR. Expression levels of IFN-G, IL-2, IL-4, IL-6, IL-17, TGF-B, IL-8, and IL-1B were significantly higher in COVID-19 patients compared with healthy controls and in both female and male patients compared with sex-matched controls. However, expression level of TNF-A was not different between COVID-19 patients and healthy controls. Expression of none of these cytokines was different between ICU-admitted patients and other patients except for IL-6 whose expression was lower in the former group compared with the latter (ratio of means = 0.33, P value = 4.82E-02). Then, we assessed diagnostic power of cytokine coding genes in differentiating between COVID-19 patients and controls. The area under curve (AUC) values ranged from 0.94 for IFN-G to 1.0 for IL-2 and IL-1B. After combining the transcript levels of all cytokines, AUC, sensitivity, and specificity values reached 100%, 100%, and 99%, respectively. For differentiation between ICU-admitted patients and other patients, IL-4 with AUC value of 0.68 had the best diagnostic power among cytokine coding genes. Expression of none of cytokine coding genes was correlated with the available clinical/demographic data including age, gender, ICU admission, or erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) levels. This study provides further evidence for contribution of "cytokine storm" in the pathobiology of moderate/severe forms of COVID-19.
由严重急性呼吸系统综合症冠状病毒 2 引起的大流行以及相关疾病，即“2019 年冠状病毒病”（COVID-19），促使研究人员揭示疾病严重程度的分子机制。有几条证据表明“细胞因子风暴”对该疾病严重形式的发病机制有影响。我们旨在评估住院的 COVID-19 患者中 9 种细胞因子编码基因的表达水平。我们从病历中收集患者的临床数据。然后，我们使用实时 PCR 评估基因的表达。与健康对照组相比，COVID-19 患者的 IFN-G、IL-2、IL-4、IL-6、IL-17、TGF-B、IL-8 和 IL-1B 的基因表达水平显著更高，并且女性和男性患者与性别匹配的对照组相比，其基因表达水平也更高。然而，TNF-A 在 COVID-19 患者和健康对照组之间的表达水平没有差异。除了 IL-6 之外，这些细胞因子中的任何一种在 ICU 住院患者和其他患者之间的表达水平都没有差异，前者的 IL-6 表达水平低于后者（平均值比=0.33，P 值=4.82E-02）。然后，我们评估了细胞因子编码基因在区分 COVID-19 患者和对照组方面的诊断能力。曲线下面积（AUC）值范围从 IFN-G 的 0.94 到 IL-2 和 IL-1B 的 1.0。结合所有细胞因子的转录水平后，AUC、敏感性和特异性值分别达到 100%、100%和 99%。对于区分 ICU 住院患者和其他患者，细胞因子编码基因中 AUC 值为 0.68 的 IL-4 具有最佳的诊断能力。细胞因子编码基因的表达与包括年龄、性别、入住 ICU 或红细胞沉降率（ESR）/C 反应蛋白（CRP）水平在内的可用临床/人口统计学数据均无相关性。本研究进一步证明了“细胞因子风暴”在 COVID-19 中/重度疾病发病机制中的作用。
