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Potential relationships between circulating gene expression of
ACE2 ,TLR4 , andIL-17 and disease severity and outcome of hospitalized patients with COVID-19Potential relationships between circulating gene expression of
ACE2 ,TLR4 , andIL-17 and disease severity and outcome of hospitalized patients with COVID-19- 住院COVID-19患者循环中
ACE2 、TLR4 和IL-17 基因表达与疾病严重程度及预后的潜在关系 - Journal of Zhejiang University-SCIENCE B Journal of Zhejiang University-SCIENCE B Vol. 27, Issue 2, Pages: 181-193(2026)
- Affiliations：
1.Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
2.Department of Medical Biochemistry and Molecular Biology, Armed Forces College of Medicine (AFCM), Cairo 1174, Egypt
3.Biochemistry Department, Faculty of Pharmacy, Sphinx University, New Assiut 71515, Egypt
4.Department of Chest Diseases, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
5.Chest Department, Faculty of Medicine, Aswan University, Aswan 81528, Egypt
6.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
7.Faculty of Biology, University of Belgrade, Belgrade 11000, Serbia
8.Department of Biochemistry, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt
9.Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Assiut 71515, Egypt
10.Clinical Pathology, Faculty of Medicine, Al-Azhar University in Assiut, Assiut 71524, Egypt
11.Department of Internal Medicine, Faculty of Medicine, Assiut University, Asyut 71515, Egypt
12.Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
13.Medical Biochemistry and Molecular Biology, Faculty of Medicine for Girls, Al-Azhar University, Cairo 11651, Egypt
14.Microbiology & Immunology Department, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
15.Physiology Department, Faculty of Medicine, Assiut University, Asyut 71515, Egypt
16.Department of Microbiology and Immunology, Faculty of Pharmacy, Sphinx University, New Assiut 71684, Egypt
17.Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Asyut 71515, Egypt
18.Department of Anesthesia and ICU, Faculty of Medicine, Assiut University, Asyut 71515, Egypt
- Funds：
DOI：10.1631/jzus.B2400345
CLC：- CSTR：
Received：14 July 2024，
Revised：2024-12-04，
Online First：10 December 2025，
Published：15 February 2026
- Accepted：
Marwa A. DAHPY,Ragaa H. SALAMA,Abdel-Raheim M. A. MEKI等.住院COVID-19患者循环中ACE2、TLR4和IL-17基因表达与疾病严重程度及预后的潜在关系[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(02):181-193.
Marwa A. DAHPY, Ragaa H. SALAMA, Abdel-Raheim M. A. MEKI, et al. Potential relationships between circulating gene expression of
ACE2 ,TLR4 , andIL-17 and disease severity and outcome of hospitalized patients with COVID-19[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(2): 181-193.Marwa A. DAHPY,Ragaa H. SALAMA,Abdel-Raheim M. A. MEKI等.住院COVID-19患者循环中ACE2、TLR4和IL-17基因表达与疾病严重程度及预后的潜在关系[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(02):181-193. DOI： 10.1631/jzus.B2400345.
Marwa A. DAHPY, Ragaa H. SALAMA, Abdel-Raheim M. A. MEKI, et al. Potential relationships between circulating gene expression of
ACE2 ,TLR4 , andIL-17 and disease severity and outcome of hospitalized patients with COVID-19[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(2): 181-193. DOI： 10.1631/jzus.B2400345.
摘要
急性呼吸窘迫综合征（ARDS）是一种进行性低氧血症，可由多种心呼吸系统或全身性疾病（如2019冠状病毒病（COVID-19））引发。严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）病毒刺突蛋白通过与细胞膜上的血管紧张素转化酶2（ACE2）受体结合，介导病毒进入细胞进行复制，并诱导信号级联反应，从而引发促炎反应。这些反应与更高的死亡率和ARDS的进展相关，最终导致患者出现多器官功能衰竭。本研究旨在分析循环中
ACE2
、Toll样受体4（
TLR4
）和白细胞介素-17（
IL-17
）基因表达水平与COVID-19疾病临床严重程度以及住院患者相关病理状况之间的关系。研究纳入了60名COVID-19患者（34名轻/中度和26名重度ARDS）和60名健康对照者。患者组还根据预后进一步细分为32名康复者和28名死亡者。除所有常规基线实验室检查（包括全血细胞计数及分类分析、C-反应蛋白（CRP）、铁蛋白和
d
-二聚体）外，本研究还通过定量聚合酶链式反应（qPCR）评估了
ACE2
、
TLR4
和
IL-17
的水平。COVID-19组及其各亚组的ACE2、TLR4和IL-17血清表达水平均显著升高，并与不同的实验室和临床参数相关。ACE2、TLR4和IL-17的血清表达水平在区分患者组与对照组方面表现出良好的准确性，其灵敏度分别为86.7%、91.7%和95.0%，特异性分别为96.7%、98.3%和98.3%，并且与COVID-19患者更严重的病程相关。因此，针对这些生物标志物的研究可能为未来的新冠患者提供额外的治疗选择。
Abstract
Acute respiratory distress syndrome (ARDS) is a form of progressive hypoxemia that can be brought on by a variety of cardiorespiratory or systemic disorders
such as coronavirus disease 2019 (COVID-19). The binding of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus spike protein to the cell membrane is mediated through its binding to angiotensin-converting enzyme 2 (ACE2) receptors
resulting in viral entry
replication
and induction of a signaling cascade inducing pro-inflammatory responses that are linked to a higher mortality rate and the progression of ARDS
leading to multi-organ failure in these patients. We aimed to analyze the relationships between circulating gene expression levels of
ACE2
Toll-like receptor 4 (
TLR4
)
and interleukin-17 (
IL-17
) and the clinical severity of COVID-19
as well as the associated pathogenic conditions
in hospitalized patients. Sixty COVID-19 patients (34 mild/moderate COVID-19 and 26 COVID-19 with severe ARDS manifestation) and 60 healthy controls were included. The patient group was also subdivided according to outcomes into 32 recoveries and 28 deaths.
ACE2
TLR4
and
IL-17
levels were assessed by quantitative polymerase chain reaction (qPCR) in addition to all rout
ine baseline laboratory investigations
including complete blood count (CBC) with differential analysis and the levels of C-reactive protein (CRP)
ferritin
and
d
-dimer. ACE2
TLR4
and IL-17 serum expression levels were significantly higher in the COVID-19 group and subgroups and were correlated with different laboratory and clinical parameters. The serum expression levels of ACE2
TLR4
and IL-17 were accurate in differentiating between the patient groups and controls
with 86.7%
91.7%
and 95.0% sensitivity and 96.7%
98.3%
and 98.3% specificity
respectively
and correlated with more severe disease courses in COVID-19 patients. Higher levels are associated with overwhelmingly distressing outcomes. Our results allow us to conclude that increased circulating gene expression levels of
ACE2
TLR4
and
IL-17
are important in assessing the severity of COVID-19. Consequently
targeting these biomarkers may offer additional therapeutic options for COVID-19 patients in the future.
关键词
Keywords
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