Abstract：
Globally, hepatitis C virus (HCV) and coronavirus disease 2019 (COVID-19) are the most common causes of death due to the lack of early predictive and diagnostic tools. Therefore, research for a new biomarker is crucial. Inflammatory biomarkers are critical central players in the pathogenesis of viral infections. IL-18, produced by macrophages in early viral infections, triggers inflammatory biomarkers and interferon production, crucial for viral host defense. Finding out IL-18 function can help understand COVID-19 pathophysiology and predict disease prognosis. Histamine and its receptors regulate allergic lung responses, with H1 receptor inhibition potentially reducing inflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. angiotensin-converting enzyme 2 (ACE-2) receptors on cholangiocytes suggest liver involvement in SARS-CoV-2 infection. The current study presents the potential impact of circulating acetylcholine, histamine, IL-18, and interferon-Alpha as diagnostic tools in HCV, COVID-19, and dual HCV-COVID-19 pathogenesis. The current study was a prospective cross-section conducted on 188 participants classified into the following four groups: Group 1 COVID-19 (n = 47), Group 2 HCV (n = 47), and Group 3 HCV-COVID-19 patients (n = 47), besides the healthy control Group 4 (n = 47). The levels of acetylcholine, histamine, IL-18, and interferon-alpha were assayed using the ELISA method. Liver and kidney functions within all groups showed a marked alteration compared to the healthy control group. Our statistical analysis found that individuals with dual infection with HCV-COVID-19 had high ferritin levels compared to other biomarkers while those with COVID-19 infection had high levels of D-Dimer. The histamine, acetylcholine, and IL-18 biomarkers in both COVID-19 and dual HCV-COVID-19 groups have shown discriminatory power, making them potential diagnostic tests for infection. These three biomarkers showed satisfactory performance in identifying HCV infection. The IFN-Alpha test performed well in the HCV-COVID-19 group and was fair in the COVID-19 group, but it had little discriminative value in the HCV group. Moreover, our findings highlighted the pivotal role of acetylcholine, histamine, IL-18, and interferon-Alpha in HCV, COVID-19, and dual HCV-COVID-19 infection. Circulating levels of acetylcholine, histamine, IL-18, and interferon-Alpha can be potential early indicators for HCV, COVID-19, and dual HCV-COVID-19 infection. We acknowledge that further large multicenter experimental studies are needed to further investigate the role biomarkers play in influencing the likelihood of infection to confirm and extend our observations and to better understand and ultimately prevent or treat these diseases.
摘要：
全球范围内,由于缺乏早期预测和诊断工具，丙型肝炎病毒（HCV）和2019年冠状病毒病（COVID-19）是最常见的死亡原因。因此,研究一种新的生物标志物是至关重要的。炎症生物标志物是病毒感染发病机理中的关键核心参与者。IL-18，在早期病毒感染中由巨噬细胞产生，引发炎症生物标志物和干扰素的产生，对于病毒宿主防御至关重要。了解IL-18的功能有助于了解COVID-19的病理生理和预测疾病预后。组胺及其受体调节过敏性肺反应，H1受体抑制可能减少严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的炎症。胆管细胞上的血管紧张素转换酶2（ACE-2）受体提示SARS-CoV-2感染涉及肝脏。目前的研究提出了循环乙酰胆碱的潜在影响，组胺,IL-18和干扰素-α作为HCV的诊断工具，COVID-19和双重HCV-COVID-19发病机制。本研究是对188名参与者进行的前瞻性横断面研究，分为以下四组：第1组COVID-19（n=47），第2组HCV（n=47），和第3组HCV-COVID-19患者（n=47），除了健康对照组4（n=47）。乙酰胆碱的水平，组胺,使用ELISA方法测定IL-18和干扰素-α。与健康对照组相比，所有组的肝肾功能均有明显变化。我们的统计分析发现，与其他生物标志物相比，HCV-COVID-19双重感染的个体具有较高的铁蛋白水平，而COVID-19感染的个体具有较高的D-二聚体水平。组胺,乙酰胆碱，和IL-18生物标志物在COVID-19和双重HCV-COVID-19组中都显示出辨别力，使它们成为潜在的感染诊断测试。这三种生物标志物在鉴定HCV感染方面表现出令人满意的性能。IFN-α检测在HCV-COVID-19组中表现良好，在COVID-19组中表现良好，但它在HCV组中几乎没有鉴别价值。此外，我们的发现强调了乙酰胆碱的关键作用，组胺,IL-18和干扰素-α在HCV，COVID-19和双重HCV-COVID-19感染。乙酰胆碱的循环水平，组胺,IL-18和干扰素-α可能是HCV的潜在早期指标，COVID-19和双重HCV-COVID-19感染。我们承认，需要进一步的大型多中心实验研究来进一步研究生物标志物在影响感染可能性中的作用，以确认和扩展我们的观察结果，并更好地理解并最终预防或治疗这些疾病。
