JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

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Potential relationships between circulating gene expression of ACE2, TLR4, and IL-17 and disease severity and outcome of hospitalized patients with COVID-19

Author(s): Marwa A. DAHPY, Ragaa H. SALAMA, Abdel-Raheim M. A. MEKI, Ashraf Zein El-ABEDEEN, Maiada K. HASHEM, Ebtsam S. ABDULKAREEM, Mohamed MOHANY, Sinisa DJURASEVIC, Amal N. IBRAHIM, Nourhan M. HUSSEIN, Shima Gafar MANSOR, Mohamed Ramadan IZZALDIN, Marwa K. KHAIRALLAH, Suzan Eid Elshishtawy IBRAHIM, Alzahra ABDELBADEA, Islam Khaled Ali HARBY, Fatma Y. A. ABBAS, Rasha M. ALI, Marwa A. SABET, Salwa Seif ElDIN, Abdelraouf M. S. ABDELRAOUF, Amira A. KAMEL
Affiliation(s): Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt; more
Corresponding email(s): Marwadahpy@aun.edu.eg
Key Words: Acute respiratory distress syndrome (ARDS); Coronavirus disease 2019 (COVID-19); Intensive care unit (ICU); Angiotensin-converting enzyme 2 (ACE2); Toll-like receptor 4 (TLR4); Interleukin-17 (IL-17); Polymerase chain reaction (PCR)

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Marwa A. DAHPY, Ragaa H. SALAMA, Abdel-Raheim M. A. MEKI, Ashraf Zein El-ABEDEEN, Maiada K. HASHEM, Ebtsam S. ABDULKAREEM, Mohamed MOHANY, Sinisa DJURASEVIC, Amal N. IBRAHIM, Nourhan M. HUSSEIN, Shima Gafar MANSOR, Mohamed Ramadan IZZALDIN, Marwa K. KHAIRALLAH, Suzan Eid Elshishtawy IBRAHIM, Alzahra ABDELBADEA, Islam Khaled Ali HARBY, Fatma Y. A. ABBAS, Rasha M. ALI, Marwa A. SABET, Salwa Seif ElDIN, Abdelraouf M. S. ABDELRAOUF, Amira A. KAMEL. Potential relationships between circulating gene expression of ACE2, TLR4, and IL-17 and disease severity and outcome of hospitalized patients with COVID-19[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2400345

@article{title="Potential relationships between circulating gene expression of ACE2, TLR4, and IL-17 and disease severity and outcome of hospitalized patients with COVID-19",
author="Marwa A. DAHPY, Ragaa H. SALAMA, Abdel-Raheim M. A. MEKI, Ashraf Zein El-ABEDEEN, Maiada K. HASHEM, Ebtsam S. ABDULKAREEM, Mohamed MOHANY, Sinisa DJURASEVIC, Amal N. IBRAHIM, Nourhan M. HUSSEIN, Shima Gafar MANSOR, Mohamed Ramadan IZZALDIN, Marwa K. KHAIRALLAH, Suzan Eid Elshishtawy IBRAHIM, Alzahra ABDELBADEA, Islam Khaled Ali HARBY, Fatma Y. A. ABBAS, Rasha M. ALI, Marwa A. SABET, Salwa Seif ElDIN, Abdelraouf M. S. ABDELRAOUF, Amira A. KAMEL",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2400345"
}

%0 Journal Article
%T Potential relationships between circulating gene expression of ACE2, TLR4, and IL-17 and disease severity and outcome of hospitalized patients with COVID-19
%A Marwa A. DAHPY
%A Ragaa H. SALAMA
%A Abdel-Raheim M. A. MEKI
%A Ashraf Zein El-ABEDEEN
%A Maiada K. HASHEM
%A Ebtsam S. ABDULKAREEM
%A Mohamed MOHANY
%A Sinisa DJURASEVIC
%A Amal N. IBRAHIM
%A Nourhan M. HUSSEIN
%A Shima Gafar MANSOR
%A Mohamed Ramadan IZZALDIN
%A Marwa K. KHAIRALLAH
%A Suzan Eid Elshishtawy IBRAHIM
%A Alzahra ABDELBADEA
%A Islam Khaled Ali HARBY
%A Fatma Y. A. ABBAS
%A Rasha M. ALI
%A Marwa A. SABET
%A Salwa Seif ElDIN
%A Abdelraouf M. S. ABDELRAOUF
%A Amira A. KAMEL
%J Journal of Zhejiang University SCIENCE B
%P 181-193
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2400345"

TY - JOUR
T1 - Potential relationships between circulating gene expression of ACE2, TLR4, and IL-17 and disease severity and outcome of hospitalized patients with COVID-19
A1 - Marwa A. DAHPY
A1 - Ragaa H. SALAMA
A1 - Abdel-Raheim M. A. MEKI
A1 - Ashraf Zein El-ABEDEEN
A1 - Maiada K. HASHEM
A1 - Ebtsam S. ABDULKAREEM
A1 - Mohamed MOHANY
A1 - Sinisa DJURASEVIC
A1 - Amal N. IBRAHIM
A1 - Nourhan M. HUSSEIN
A1 - Shima Gafar MANSOR
A1 - Mohamed Ramadan IZZALDIN
A1 - Marwa K. KHAIRALLAH
A1 - Suzan Eid Elshishtawy IBRAHIM
A1 - Alzahra ABDELBADEA
A1 - Islam Khaled Ali HARBY
A1 - Fatma Y. A. ABBAS
A1 - Rasha M. ALI
A1 - Marwa A. SABET
A1 - Salwa Seif ElDIN
A1 - Abdelraouf M. S. ABDELRAOUF
A1 - Amira A. KAMEL
J0 - Journal of Zhejiang University Science B
SP - 181
EP - 193
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2400345"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

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 routine 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.

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

Marwa A. DAHPY^1,2, Ragaa H. SALAMA¹, Abdel-Raheim M. A. MEKI^1,3, Ashraf Zein El-ABEDEEN⁴, Maiada K. HASHEM⁴, Ebtsam S. ABDULKAREEM⁵, Mohamed MOHANY⁶, Sinisa DJURASEVIC⁷, Amal N. IBRAHIM⁸, Nourhan M. HUSSEIN⁸, Shima Gafar MANSOR⁹, Mohamed Ramadan IZZALDIN¹⁰, Marwa K. KHAIRALLAH¹¹, Suzan Eid Elshishtawy IBRAHIM¹², Alzahra ABDELBADEA¹³, Islam Khaled Ali HARBY¹⁴, Fatma Y. A. ABBAS¹⁵, Rasha M. ALI¹⁵, Marwa A. SABET¹⁶, Salwa Seif ElDIN¹⁷, Abdelraouf M. S. ABDELRAOUF¹⁸, Amira A. KAMEL¹
¹Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
²Department of Medical Biochemistry and Molecular Biology, Armed Forces College of Medicine (AFCM), Cairo 1174, Egypt
³Biochemistry Department, Faculty of Pharmacy, Sphinx University, New Assiut 71515, Egypt
⁴Department of Chest Diseases, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
⁵Chest Department, Faculty of Medicine, Aswan University, Aswan 81528, Egypt
⁶Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
⁷Faculty of Biology, University of Belgrade, Belgrade 11000, Serbia
⁸Department of Biochemistry, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt
⁹Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Assiut 71515, Egypt
¹⁰Clinical Pathology, Faculty of Medicine, Al-Azhar University in Assiut, Assiut 71524, Egypt
¹¹Department of Internal Medicine, Faculty of Medicine, Assiut University, Asyut 71515, Egypt
¹²Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
¹³Medical Biochemistry and Molecular Biology, Faculty of Medicine for Girls, Al-Azhar University, Cairo 11651, Egypt
¹⁴Microbiology & Immunology Department, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
¹⁵Physiology Department, Faculty of Medicine, Assiut University, Asyut 71515, Egypt
¹⁶Department of Microbiology and Immunology, Faculty of Pharmacy, Sphinx University, New Assiut 71684, Egypt
¹⁷Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Asyut 71515, Egypt
¹⁸Department of Anesthesia and ICU, Faculty of Medicine, Assiut University, Asyut 71515, Egypt
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。

关键词组：急性呼吸窘迫综合征（ARDS）；2019冠状病毒病（COVID-19）；重症监护室（ICU）；血管紧张素转化酶2（ACE2）；Toll样受体4（TLR4）；白细胞介素-17（IL-17）；聚合酶链式反应（PCR）

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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

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