Department of Biochemistry, Faculty of Medicine, Minia University, Minia, Egypt.
Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, 61511, Egypt.
Sci Rep. 2023 Mar 2;13(1):3531. doi: 10.1038/s41598-023-30474-6.
Host microRNAs can influence the cytokine storm associated SARS-CoV-2 infection and proposed as biomarkers for COVID-19 disease. In the present study, serum MiRNA-106a and miRNA-20a were quantified by real time-PCR in 50 COVID-19 patients hospitalized at Minia university hospital and 30 healthy volunteers. Profiles of serum inflammatory cytokines (TNF-α, IFN-γ, and IL-10) and TLR4 were analyzed by Eliza in patients and controls. A highly significant decrease (P value = 0.0001) in the expressions of miRNA-106a and miRNA-20a was reported in COVID-19 patients compared to controls. A significant decrease in the levels of miRNA-20a was also reported in patients with lymphopenia, patients having chest CT severity score (CSS) > 19 and in patients having O saturation less than 90%. Significantly higher levels of TNF-α, IFN-γ, IL-10 and TLR4 were reported in patients compared to controls. IL-10 and TLR4 levels were significantly higher in patients having lymphopenia. TLR-4 level was higher in patients with CSS > 19 and in patients with hypoxia. Using univariate logistic regression analysis, miRNA-106a, miRNA-20a, TNF-α, IFN-γ, IL-10 and TLR4 were identified as good predictors of disease. Receiver operating curve showed that the downregulation of miRNA-20a in patients having lymphopenia, patients with CSS > 19 and patients with hypoxia could be a potential biomarker with AUC = 0.68 ± 0.08, AUC = 0.73 ± 0.07 and AUC = 0.68 ± 0.07 respectively. Also, ROC curve showed accurate association between the increase of serum IL-10 and TLR-4 and lymphopenia among COVID-19 patients with AUC = 0.66 ± 0.08 and AUC = 0.73 ± 0.07 respectively. ROC curve showed also that serum TLR-4 could be a potential marker for high CSS with AUC = 0.78 ± 0.06. A negative correlation was detected between miRNA-20a with TLR-4 (r = - 0.30, P value = 0.03). We concluded that, miR-20a, is a potential biomarker of COVID-19 severity and blockade of IL-10 and TLR4 may constitute a novel therapy for COVID-19 patients.
宿主 microRNAs 可影响与 SARS-CoV-2 感染相关的细胞因子风暴，并被提议作为 COVID-19 疾病的生物标志物。在本研究中，通过实时 PCR 在米尼亚大学医院的 50 名 COVID-19 患者和 30 名健康志愿者中定量检测血清 MiRNA-106a 和 miRNA-20a。通过 Eliza 在患者和对照中分析血清炎症细胞因子（TNF-α、IFN-γ 和 IL-10）和 TLR4 的谱。与对照组相比，COVID-19 患者的 miRNA-106a 和 miRNA-20a 表达显著降低（P 值=0.0001）。还报道了 miRNA-20a 在淋巴细胞减少症患者、胸部 CT 严重程度评分（CSS）>19 的患者和饱和度低于 90%的患者中的水平显著降低。与对照组相比，患者的 TNF-α、IFN-γ、IL-10 和 TLR4 水平显著升高。与淋巴细胞减少症患者相比，IL-10 和 TLR4 水平更高。CSS>19 的患者和缺氧患者的 TLR-4 水平更高。使用单变量逻辑回归分析，miRNA-106a、miRNA-20a、TNF-α、IFN-γ、IL-10 和 TLR4 被鉴定为疾病的良好预测因子。接收者操作曲线表明，在淋巴细胞减少症患者、CSS>19 的患者和缺氧患者中，miRNA-20a 的下调可能是 AUC=0.68±0.08、AUC=0.73±0.07 和 AUC=0.68±0.07 的潜在生物标志物。此外，ROC 曲线显示 COVID-19 患者中血清 IL-10 和 TLR-4 与淋巴细胞减少症之间存在准确关联，AUC 分别为 0.66±0.08 和 0.73±0.07。ROC 曲线还表明，血清 TLR-4 可能是 CSS 较高的潜在标志物，AUC=0.78±0.06。检测到 miRNA-20a 与 TLR-4 之间存在负相关（r=-0.30，P 值=0.03）。我们得出结论，miR-20a 是 COVID-19 严重程度的潜在生物标志物，阻断 IL-10 和 TLR4 可能构成 COVID-19 患者的新疗法。
