Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates.
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Life Sci. 2022 Sep 1;304:120703. doi: 10.1016/j.lfs.2022.120703. Epub 2022 Jun 11.
Biologically active molecules cytokines and growth factors (GFs) are critical regulators of tissue injury/repair and emerge as key players in COVID-19 pathophysiology. However, specific disease stage of GFs dysregulation and, whether these GFs have associations with thromboembolism and tissue injury/repair in COVID-19 remain vague.
GF profiling in hospitalized moderate (non-ICU) and critically ill (ICU) COVID-19 patients was performed through legendPlex assay.
Investigation revealed profound elevation of VEGF, PDGFs, EGF, TGF-α, FGF-basic, and erythropoietin (EPO) in moderate cases and decline or trend of decline with disease advancement. We found strong positive correlations of plasma VEGF, PDGFs, and EPO with endothelial dysfunction markers P-selectin and sCD40L. Interestingly, the HGF and G-CSF were upregulated at the moderate stage and remained elevated at the severe stage of COVID-19. Moreover, strong negative correlations of PDGFs (r = 0.238, P = 0.006), EPO (r = 0.18, P = 0.01) and EGF (r = 0.172, P = 0.02) and positive correlation of angiopoietin-2 (r = 0.267, P = 0.003) with D-dimer, a marker of thromboembolism, was observed. Further, plasma PDGFs (r = 0.199, P = 0.01), EPO (r = 0.115, P = 0.02), and EGF (r = 0.108, P = 0.07) exhibited negative correlations with tissue injury marker, myoglobin.
Taken together, unlike cytokines, most of the assessed GFs were upregulated at the moderate stage of COVID-19. The induction of GFs likely occurs due to endothelial dysfunction and may counter the adverse effects of cytokine storms which is reflected by inverse correlations of PDGFs, EPO, and EGF with thromboembolism and tissue injury markers. The findings suggest that the assessed GFs play differential roles in the pathogenesis of COVID-19.
细胞因子和生长因子（GFs）等生物活性分子是组织损伤/修复的关键调节剂，也是 COVID-19 病理生理学中的关键参与者。然而，GF 调节的具体疾病阶段，以及这些 GFs 是否与 COVID-19 中的血栓栓塞和组织损伤/修复有关，仍不清楚。
通过 legendPlex 测定法对住院的中度（非 ICU）和重症（ICU）COVID-19 患者进行 GFs 分析。
研究结果显示，VEGF、PDGFs、EGF、TGF-α、FGF-basic 和促红细胞生成素（EPO）在中度病例中明显升高，随着疾病的进展而下降或呈下降趋势。我们发现，血浆 VEGF、PDGFs 和 EPO 与内皮功能障碍标志物 P-选择素和 sCD40L 呈强正相关。有趣的是，HGF 和 G-CSF 在中度阶段上调，并在 COVID-19 的严重阶段仍保持升高。此外，PDGFs（r=0.238，P=0.006）、EPO（r=0.18，P=0.01）和 EGF（r=0.172，P=0.02）的负相关性很强，以及血管生成素-2（r=0.267，P=0.003）与血栓栓塞标志物 D-二聚体呈正相关。此外，血浆 PDGFs（r=0.199，P=0.01）、EPO（r=0.115，P=0.02）和 EGF（r=0.108，P=0.07）与组织损伤标志物肌红蛋白呈负相关。
综上所述，与细胞因子不同，大多数评估的 GFs 在 COVID-19 的中度阶段上调。GFs 的诱导可能是由于内皮功能障碍引起的，并且可能抵消细胞因子风暴的不利影响，这反映在 PDGFs、EPO 和 EGF 与血栓栓塞和组织损伤标志物呈负相关。这些发现表明，评估的 GFs 在 COVID-19 的发病机制中发挥不同的作用。
