

无数据
Scan QR Code
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
收稿:2024-07-14,
修回:2024-12-04,
网络首发:2025-12-10,
纸质出版:2026-02-15
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
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
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。
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.
Alabsi S , Dhole A , Hozayen S , et al. , 2023 . Angiotensin-converting enzyme 2 expression and severity of SARS-CoV-2 infection . Microorganisms , 11 ( 3 ): 612 . https://doi.org/10.3390/microorganisms11030612 https://doi.org/10.3390/microorganisms11030612
Alturaiki W , Alkadi H , Alamri S , et al. , 2023 . Association between the expression of toll-like receptors, cytokines, and homeostatic chemokines in SARS-CoV-2 infection and COVID-19 severity . Heliyon , 9 ( 1 ): e12653 . https://doi.org/10.1016/j.heliyon.2022.e12653 https://doi.org/10.1016/j.heliyon.2022.e12653
Au Yeung SL , Wong THT , He BT , et al. , 2023 . Does ACE2 mediate the detrimental effect of exposures related to COVID-19 risk: a Mendelian randomization investigation . J Med Virol , 95 ( 1 ): e28205 . https://doi.org/10.1002/jmv.28205 https://doi.org/10.1002/jmv.28205
Ayhan E , Öztürk M , An İ , et al. , 2020 . Potential role of anti-interleukin-17 in COVID-19 treatment . Dermatol Ther , 33 ( 4 ): e13715 . https://doi.org/10.1111/dth.13715 https://doi.org/10.1111/dth.13715
Azkur AK , Akdis M , Azkur D , et al. , 2020 . Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19 . Allergy , 75 ( 7 ): 1564 - 1581 . https://doi.org/10.1111/all.14364 https://doi.org/10.1111/all.14364
Bartolák-Suki E , Mondoñedo JR , Suki B , 2022 . Mechano-inflammatory sensitivity of ACE2: implications for the regional distribution of SARS-CoV-2 injury in the lung . Respir Physiol Neurobiol , 296 : 103804 . https://doi.org/10.1016/j.resp.2021.103804 https://doi.org/10.1016/j.resp.2021.103804
Brandão SCS , de Oliveira Xavier Ramos J , Dompieri LT , et al. , 2021 . Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities? Cytokine Growth Factor Rev , 58 : 102 - 110 . https://doi.org/10.1016/j.cytogfr.2020.09.002 https://doi.org/10.1016/j.cytogfr.2020.09.002
Chee J , Chern B , Loh WS , et al. , 2023 . Pathophysiology of SARS-CoV-2 infection of nasal respiratory and olfactory epithelia and its clinical impact . Curr Allergy Asthma Rep , 23 ( 2 ): 121 - 131 . https://doi.org/10.1007/s11882-022-01059-6 https://doi.org/10.1007/s11882-022-01059-6
Choudhury A , Mukherjee S , 2020 . In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs . J Med Virol , 92 ( 10 ): 2105 - 2113 . https://doi.org/10.1002/jmv.25987 https://doi.org/10.1002/jmv.25987
Corpetti C , Del Re A , Seguella L , et al. , 2021 . Cannabidiol inhibits SARS-Cov-2 spike (S) protein-induced cytotoxicity and inflammation through a PPARγ-dependent TLR4/NLRP3/Caspase-1 signaling suppression in Caco-2 cell line . Phytother Res , 35 ( 12 ): 6893 - 6903 . https://doi.org/10.1002/ptr.7302 https://doi.org/10.1002/ptr.7302
Darif D , Hammi I , Kihel A , et al. , 2021 . The pro-inflammatory cytokines in COVID-19 pathogenesis: what goes wrong? Microb Pathog , 153 : 104799 . https://doi.org/10.1016/j.micpath.2021.104799 https://doi.org/10.1016/j.micpath.2021.104799
del Carmen Chávez-Ocaña S , Bravata-Alcántara JC , Cortés-Ortiz IA , et al. , 2023 . Parameters to predict the outcome of severe and critical COVID-19 patients when admitted to the hospital . J Clin Med , 12 ( 4 ): 1323 . https://doi.org/10.3390/jcm12041323 https://doi.org/10.3390/jcm12041323
Dorneles GP , Teixeira PC , Peres A , et al. , 2023 . Endotoxin tolerance and low activation of TLR-4/NF-κB axis in monocytes of COVID-19 patients . J Mol Med , 101 ( 1-2 ): 183 - 195 . https://doi.org/10.1007/s00109-023-02283-x https://doi.org/10.1007/s00109-023-02283-x
Fu LW , Wang BY , Yuan TW , et al. , 2020 . Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis . J Infect , 80 ( 6 ): 656 - 665 . https://doi.org/10.1016/j.jinf.2020.03.041 https://doi.org/10.1016/j.jinf.2020.03.041
Fujishima S , 2023 . Guideline-based management of acute respiratory failure and acute respiratory distress syndrome . J Intensive Care , 11 : 10 . https://doi.org/10.1186/s40560-023-00658-3 https://doi.org/10.1186/s40560-023-00658-3
Gadanec LK , McSweeney KR , Qaradakhi T , et al. , 2021 . Can SARS-CoV-2 virus use multiple receptors to enter host cells? Int J Mol Sci , 22 ( 3 ): 992 . https://doi.org/10.3390/ijms22030992 https://doi.org/10.3390/ijms22030992
Ghazavi A , Ganji A , Keshavarzian N , et al. , 2021 . Cytokine profile and disease severity in patients with COVID-19 . Cytokine , 137 : 155323 . https://doi.org/10.1016/j.cyto.2020.155323 https://doi.org/10.1016/j.cyto.2020.155323
Hu BY , Huang SY , Yin LH , 2021 . The cytokine storm and COVID-19 . J Med Virol , 93 ( 1 ): 250 - 256 . https://doi.org/10.1002/jmv.26232 https://doi.org/10.1002/jmv.26232
Jose SP , Ratheesh M , Sheethal S , et al. , 2022 . Anti-inflammatory effect of Kaba Sura Kudineer ( AYUSH approved COVID-19 drug )-A Siddha poly-herbal formulation against lipopolysaccharide induced inflammatory response in RAW-264.7 macrophages cells . J Ethnopharmacol , 283 : 114738 . https://doi.org/10.1016/j.jep.2021.114738 https://doi.org/10.1016/j.jep.2021.114738
Khanmohammadi S , Rezaei N , 2021 . Role of Toll-like receptors in the pathogenesis of COVID-19 . J Med Virol , 93 ( 5 ): 2735 - 2739 . https://doi.org/10.1002/jmv.26826 https://doi.org/10.1002/jmv.26826
Kogan E , Berezovskiy Y , Blagova O , et al. , 2022 . Morphologically, immunohistochemically and PCR proven lymphocytic viral peri-, endo-, myocarditis in patients with fatal COVID-19 . Diagn Pathol , 17 : 31 . https://doi.org/10.1186/s13000-022-01207-6 https://doi.org/10.1186/s13000-022-01207-6
Kuzmich NN , Sivak KV , Chubarev VN , et al. , 2017 . TLR4 signaling pathway modulators as potential therapeutics in inflammation and sepsis . Vaccines , 5 ( 4 ): 34 . https://doi.org/10.3390/vaccines5040034 https://doi.org/10.3390/vaccines5040034
Liang WH , Guan WJ , Li CC , et al. , 2020 . Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China . Eur Respir J , 55 ( 6 ): 2000562 . https://doi.org/10.1183/13993003.00562-2020 https://doi.org/10.1183/13993003.00562-2020
Liu S , Han LP , Li JL , et al. , 2022 . Electrochemical detection of ACE2 as a biomarker for diagnosis of COVID-19 and potential male infertility . Biosens Bioelectron , 198 : 113788 . https://doi.org/10.1016/j.bios.2021.113788 https://doi.org/10.1016/j.bios.2021.113788
Luo M , Hu LJ , Li DD , et al. , 2017 . MD-2 regulates LPS-induced NLRP3 inflammasome activation and IL-1beta secretion by a MyD88/NF-κB-dependent pathway in alveolar macrophages cell line . Mol Immunol , 90 : 1 - 10 . https://doi.org/10.1016/j.molimm.2017.06.035 https://doi.org/10.1016/j.molimm.2017.06.035
Manik M , Singh RK , 2022 . Role of toll-like receptors in modulation of cytokine storm signaling in SARS-CoV-2-induced COVID-19 . J Med Vorol , 94 ( 3 ): 869 - 877 . https://doi.org/10.1002/jmv.27405 https://doi.org/10.1002/jmv.27405
Megna M , Napolitano M , Fabbrocini G , 2020 . May IL-17 have a role in COVID-19 infection? Med Hypothese , 140 : 109749 . https://doi.org/10.1016/j.mehy.2020.109749 https://doi.org/10.1016/j.mehy.2020.109749
Montazersaheb S , Hosseiniyan Khatibi SM , Hejazi MS , et al. , 2022 . COVID-19 infection: an overview on cytokine storm and related interventions . Virol J , 19 : 92 . https://doi.org/10.1186/s12985-022-01814-1 https://doi.org/10.1186/s12985-022-01814-1
Ni YQ , Zeng HH , Song XW , et al. , 2022 . Potential metal-related strategies for prevention and treatment of COVID-19 . Rare Met , 41 ( 4 ): 1129 - 1141 . https://doi.org/10.1007/s12598-021-01894-y https://doi.org/10.1007/s12598-021-01894-y
Oudit GY , Wang KM , Viveiros A , et al. , 2023 . Angiotensin-converting enzyme 2—at the heart of the COVID-19 pandemic . Cell , 186 ( 5 ): 906 - 922 . https://doi.org/10.1016/j.cell.2023.01.039 https://doi.org/10.1016/j.cell.2023.01.039
Pan Y , 2023 . Angiotensin-converting enzyme 2 G8790A polymorphisms are associated with COVID-19 severity . J Infect Dev Ctries , 17 ( 6 ): 819 - 825 . https://doi.org/10.3855/jidc.17762 https://doi.org/10.3855/jidc.17762
Pascarella G , Strumia A , Piliego C , et al. , 2020 . COVID-19 diagnosis and management: a comprehensive review . J Intern Med , 288 ( 2 ): 192 - 206 . https://doi.org/10.1111/joim.13091 https://doi.org/10.1111/joim.13091
Rahman M , Irmler M , Keshavan S , et al. , 2021 . Differential effect of SARS-CoV-2 spike glycoprotein 1 on human bronchial and alveolar lung mucosa models: implications for pathogenicity . Viruses , 13 ( 12 ): 2537 . https://doi.org/10.3390/v13122537 https://doi.org/10.3390/v13122537
Sánchez-Díez S , Gómez-Ollés C , Cruz MJ , et al. , 2023 . Biomarker profiles associated with COVID-19 severity and mortality . Curr Issues Mol Biol , 45 ( 3 ): 1998 - 2012 . https://doi.org/10.3390/cimb45030128 https://doi.org/10.3390/cimb45030128
Sodhi PV , Sidime F , Tarazona DD , et al. , 2023 . A closer look at ACE2 signaling pathway and processing during COVID-19 infection: identifying possible targets . Vaccines , 11 ( 1 ): 13 . https://doi.org/10.3390/vaccines11010013 https://doi.org/10.3390/vaccines11010013
Sohn KM , Lee SG , Kim HJ , et al. , 2020 . COVID-19 patients upregulate toll-like receptor 4-mediated inflammatory signaling that mimics bacterial sepsis . J Korean Med Sci , 35 ( 38 ): e343 . https://doi.org/10.3346/jkms.2020.35.e343 https://doi.org/10.3346/jkms.2020.35.e343
Sultan RH , Abdallah M , Ali TM , et al. , 2022 . The associations between cytokine levels, kidney and heart function biomarkers, and expression levels of angiotensin-converting enzyme-2 and neuropilin-1 in COVID-19 patients . Vaccines , 10 ( 7 ): 1045 . https://doi.org/10.3390/vaccines10071045 https://doi.org/10.3390/vaccines10071045
Taha SI , Shata AK , Baioumy SA , et al. , 2021 . Toll-like receptor 4 polymorphisms (896A/G and 1196C/T) as an indicator of COVID-19 severity in a convenience sample of Egyptian patients . J Inflamm Res , 14 : 6293 - 6303 . https://doi.org/10.2147/jir.s343246 https://doi.org/10.2147/jir.s343246
World Health Organization , 2020 . Pandemic Influenza Severity Assessment (PISA): A WHO guide to assess the severity of influenza epidemics and pandemics . World Health Organization, Geneva. https://www.who.int/news/item/05-07-2024-pandemic-and-seasonal-influenza-severity-assessment-guidance-updated https://www.who.int/news/item/05-07-2024-pandemic-and-seasonal-influenza-severity-assessment-guidance-updated
Wu X , Xia T , Shin WJ , et al. , 2022 . Viral mimicry of interleukin-17A by SARS-CoV-2 ORF8 . mBio , 13 ( 2 ): e00402-22 . https://doi.org/10.1128/mbio.00402-22 https://doi.org/10.1128/mbio.00402-22
Xu Z , Shi L , Wang YJ , et al. , 2020 . Pathological findings of COVID-19 associated with acute respiratory distress syndrome . Lancet Respir Med , 8 ( 4 ): 420 - 422 . https://doi.org/10.1016/s2213-2600(20)30076-x https://doi.org/10.1016/s2213-2600(20)30076-x
Zheng M , 2022 . ACE2 and COVID-19 susceptibility and severity . Aging Dis , 13 ( 2 ): 360 - 372 . https://doi.org/10.14336/ad.2021.0805 https://doi.org/10.14336/ad.2021.0805
0
浏览量
0
Downloads
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621