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乙酰胆碱、组胺、IL-18 和干扰素-α作为丙型肝炎病毒、2019 年冠状病毒病和丙型肝炎病毒-2019 年冠状病毒病双重感染患者的诊断生物标志物的生化意义。

Biochemical implication of acetylcholine, histamine, IL-18, and interferon-alpha as diagnostic biomarkers in hepatitis C virus, coronavirus disease 2019, and dual hepatitis C virus-coronavirus disease 2019 patients.

机构信息

Department of Biotechnology, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt.

Biochemistry and Molecular Biology Department, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt.

出版信息

J Med Virol. 2024 Aug;96(8):e29857. doi: 10.1002/jmv.29857.

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)是导致死亡的最常见原因。因此,研究新的生物标志物至关重要。炎症生物标志物是病毒感染发病机制中的关键核心参与者。巨噬细胞在早期病毒感染中产生的白细胞介素 18(IL-18)触发炎症生物标志物和干扰素的产生,这对病毒宿主防御至关重要。了解 IL-18 的功能有助于理解 COVID-19 的病理生理学并预测疾病预后。组胺及其受体调节过敏性肺反应,H1 受体抑制可能会减少严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染中的炎症。胆管细胞上的血管紧张素转换酶 2(ACE-2)受体表明 SARS-CoV-2 感染涉及肝脏。本研究提出了循环乙酰胆碱、组胺、IL-18 和干扰素-α作为 HCV、COVID-19 和双重 HCV-COVID-19 发病机制诊断工具的潜在影响。本研究是一项前瞻性横断面研究,共纳入 188 名参与者,分为以下四组:COVID-19 组 1(n=47)、HCV 组 2(n=47)和双重 HCV-COVID-19 患者组 3(n=47),以及健康对照组 4(n=47)。使用 ELISA 法检测乙酰胆碱、组胺、IL-18 和干扰素-α的水平。与健康对照组相比,所有组的肝肾功能均有明显改变。我们的统计分析发现,与其他生物标志物相比,同时感染 HCV-COVID-19 的个体铁蛋白水平较高,而感染 COVID-19 的个体 D-二聚体水平较高。COVID-19 和双重 HCV-COVID-19 组中的组胺、乙酰胆碱和 IL-18 生物标志物具有鉴别能力,使其成为感染的潜在诊断测试。这三种生物标志物在识别 HCV 感染方面表现出令人满意的性能。IFN-Alpha 试验在 HCV-COVID-19 组中表现良好,在 COVID-19 组中表现良好,但在 HCV 组中鉴别价值不大。此外,我们的研究结果强调了乙酰胆碱、组胺、IL-18 和干扰素-α在 HCV、COVID-19 和双重 HCV-COVID-19 感染中的关键作用。循环乙酰胆碱、组胺、IL-18 和干扰素-α水平可能是 HCV、COVID-19 和双重 HCV-COVID-19 感染的早期潜在指标。我们认识到,需要进一步进行大型多中心实验研究,以进一步研究生物标志物在影响感染可能性方面的作用,从而证实和扩展我们的观察结果,并更好地了解和最终预防或治疗这些疾病。

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