Serum Soluble Angiotensin-Converting Enzyme-2 Level and Its Potential Association With The Renin-Angiotensin-Aldosterone System in Non-Hypertensive Iraqi COVID-19 Patients: An Observational Study

Authors

  • Mohammed A. Turki Department of Clinical Laboratory Science, College of Pharmacy, University of Baghdad, Baghdad, Iraq.
  • Ali A. Kasim Department of Clinical Laboratory Science, College of Pharmacy, University of Baghdad, Baghdad, Iraq.

DOI:

https://doi.org/10.31351/vol32issSuppl.pp91-98

Abstract

Background: The novel coronavirus disease (COVID-19) is caused by Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) which utilizes angiotensin converting enzyme2 (ACE2) to invade the host cells. This membrane-bound peptidase is widely distributed in the body; its activity antagonizes the renin-angiotensin-aldosterone system (RAAS). Once SARS-Cov2 enters the cell, it causes downregulation of ACE2, resulting in the unopposed activation of RAAS. The unregulated activity of the RAAS system can deteriorate the prognosis in COVID-19 patients. A soluble form of ACE2 (sACE2) was reported to have a role in the SARS-Cov2 invasion of the susceptible cells.

Aim of the study: This study aims to investigate the potential association of serum levels of sACE2 and RAAS components in severe COVID-19 patients compared to healthy individuals.

Methods: Eighty-five participants enrolled in the study were grouped into 45 non-hypertensive severe COVID-19 patients and 40 healthy individuals with comparable age and gender. Serum levels of sACE2, renin, angiotensin 2, and aldosterone by ELISA, and serum potassium level was measured by turbidimetric method.

Results: The results showed a significant difference in the serum levels of sACE2 (lower), renin, angiotensin 2, and aldosterone (higher) in COVID-19 patients compared to the control subjects (p-value <0.001; for all.

Conclusion: Non-hypertensive severe COVID-19 patients have lower sACE2 and higher RAAS peptide levels, and they can serve as diagnostic markers of severe COVID-19 patients.

Recommendations: we recommend a future study with a larger sample size that enrolls COVID-19 patients with different severity levels.

Keywords: Aldosterone, Angiotensin, COVID-19, Renin, Soluble angiotensin converting enzyme 2

References

Adil MT, Rahman R, Whitelaw D, Jain V, Al-Taan O, Rashid F, et al. SARS-CoV-2 and the pandemic of COVID-19. Postgraduate medical journal. 2021;97(1144):110-6.

Joshi M, Deshpande JD. Polymerase chain reaction: methods, principles and application. International Journal of Biomedical Research. 2010;2(1):81-97.

Shareef LG, Abdulwahab SM. Trends in covid-19 therapeutic modalities: A narrative literature. Eur J Pharm Med Res. 2020;7:757-67.

Sabah Khalid S, Mohamed Ali Z, Shareef LG. Levels of cardiac troponin-T and LDL-C to HDL-C ratio of hospitalized COVID-19 patients: A case-control study. F1000Research. 2022;11:860.

Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical characteristics of coronavirus disease 2019 in China. New England journal of medicine. 2020;382(18):1708-20.

Alqubbanchi FB, Al-Hamadani FY. A Pharmacoeconomics Study for Anticoagulants used for Hospitalized COVID-19 Patients in Al-Najaf Al-Ashraf city–Iraq (Conference Paper). Iraqi Journal of Pharmaceutical Sciences. 2021;30(Suppl.):48-59.

Bonyan FA, Shareef LG, Al-waily A, Abdulrazaq AA, Al-Rubayee WA. COVID-19 clinical characteristics and outcomes in 60 hospitalized Iraqi patients-Case series. Medical Science. 2020:2251-8.

Bai Y, Yao L, Wei T, Tian F, Jin D-Y, Chen L, et al. Presumed asymptomatic carrier transmission of COVID-19. Jama. 2020;323(14):1406-7.

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The lancet. 2020;395(10223):507-13.

Khalid SS, Ali ZM, Raheem MF. Serum Levels of Homocysteine, Troponin-I, and High Sensitive C-Reactive Protein in Iraqi COVID-19 Patients. J Contemp Med Sci| Vol. 2022;8(3):189-93.

Khalid SS, Ali ZM, Shareef LG. Levels of cardiac troponin-T and LDL-C to HDL-C ratio of hospitalized COVID-19 patients: A case-control study. F1000Research. 2022;11(860):860.

Shareef LG, Al-Hussainy AF, Hameed SM. COVID-19 vaccination hesitancy among Iraqi general population between beliefs and barriers: An observational study. F1000Research. 2022;11:334.

Shareef LG. COVID-19 vaccine coverage and the necessity of its urgent development towards Omicron the new SARS CoV-2 B. 1.1. 529 variant. GSC Biological and Pharmaceutical Sciences. 2021;17(3):058-60.

Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. nature. 2020;579(7798):270-3.

Naser NH, Alibeg AAA. Exacerbation of COVID 19 in Hypertensive Patients? A review? Iraqi Journal of Pharmaceutical Sciences. 2021;30(2):23-30.

Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J, et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. Journal of virology. 2005;79(23):14614-21.

Hou YJ, Okuda K, Edwards CE, Martinez DR, Asakura T, Dinnon KH, 3rd, et al. SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell. 2020;182(2):429-46.e14.

McCray PB, Jr., Pewe L, Wohlford-Lenane C, Hickey M, Manzel L, Shi L, et al. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. Journal of virology. 2007;81(2):813-21.

Santos RAS, Sampaio WO, Alzamora AC, Motta-Santos D. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7). 2018;98(1):505-53.

Sodhi CP, Wohlford-Lenane C, Yamaguchi Y, Prindle T, Fulton WB, Wang S, et al. Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg(9) bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration. American journal of physiology Lung cellular and molecular physiology. 2018;314(1):L17-l31.

Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436(7047):112-6.

Paz Ocaranza M, Riquelme JA, García L, Jalil JE, Chiong M, Santos RA, et al. Counter-regulatory renin–angiotensin system in cardiovascular disease. Nature Reviews Cardiology. 2020;17(2):116-29.

Singh KD, Karnik SS. Angiotensin receptors: structure, function, signaling and clinical applications. Journal of cell signaling. 2016;1(2):111.

Kuba K, Yamaguchi T, Penninger JM. Angiotensin-Converting Enzyme 2 (ACE2) in the Pathogenesis of ARDS in COVID-19. Frontiers in immunology. 2021;12:732690.

Yeung ML, Teng JLL, Jia L, Zhang C, Huang C, Cai JP, et al. Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system. Cell. 2021;184(8):2212-28.e12.

Krishnamurthy S, Lockey RF, Kolliputi N. Soluble ACE2 as a potential therapy for COVID-19. American journal of physiology Cell physiology. 2021;320(3):C279-c81.

Jia HP, Look DC, Tan P, Shi L, Hickey M, Gakhar L, et al. Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia. American journal of physiology Lung cellular and molecular physiology. 2009;297(1):L84-96.

Hussain E, Hasan M, Rahman MA, Lee I, Tamanna T, Parvez MZ. CoroDet: A deep learning based classification for COVID-19 detection using chest X-ray images. Chaos, Solitons & Fractals. 2021;142:110495.

Long C, Xu H, Shen Q, Zhang X, Fan B, Wang C, et al. Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? European journal of radiology. 2020;126:108961.

Control CfD, Prevention. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). 2020.

Health NIo. Clinical spectrum of SARS-CoV-2 infection. National Institutes of Health: Bethesda, MD, USA. 2021;12:2021.

Aydin S. A short history, principles, and types of ELISA, and our laboratory experience with peptide/protein analyses using ELISA. Peptides. 2015;72:4-15.

Tubino M, Souza RLd, Hoehr NF. Rapid quantitative turbidimetric spot test analysis of potassium in blood serum. Journal of the Brazilian Chemical Society. 2004;15:635-9.

Carey RM. Update on angiotensin AT2 receptors. Current opinion in nephrology and hypertension. 2017;26(2):91.

Kuba K, Imai Y, Penninger JM. Angiotensin-converting enzyme 2 in lung diseases. Current opinion in pharmacology. 2006;6(3):271-6.

Rieder M, Wirth L, Pollmeier L, Jeserich M, Goller I, Baldus N, et al. Serum ACE2, angiotensin II, and aldosterone levels are unchanged in patients with COVID-19. American journal of hypertension. 2021;34(3):278-81.

Rysz S, Al-Saadi J, Sjöström A, Farm M, Campoccia Jalde F, Plattén M, et al. COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system. Nature Communications. 2021;12(1):2417.

Kutz A, Conen A, Gregoriano C, Haubitz S, Koch D, Domenig O, et al. Renin-angiotensin-aldosterone system peptide profiles in patients with COVID-19. European journal of endocrinology. 2021;184(4):543-52.

Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Science China Life sciences. 2020;63(3):364-74.

Kintscher U, Slagman A, Domenig O, Röhle R, Konietschke F, Poglitsch M, et al. Plasma Angiotensin Peptide Profiling and ACE (Angiotensin-Converting Enzyme)-2 Activity in COVID-19 Patients Treated With Pharmacological Blockers of the Renin-Angiotensin System. Hypertension (Dallas, Tex : 1979). 2020;76(5):e34-e6.

Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nature medicine. 2005;11(8):875-9.

Remková A, Remko M. The role of renin-angiotensin system in prothrombotic state in essential hypertension. Physiological Research. 2010;59(1):13-23.

Dandona P, Dhindsa S, Ghanim H, Chaudhuri A. Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade. Journal of human hypertension. 2007;21(1):20-7.

Greco A, Rabito G, Pironi M, Bissig M, Parlato S, Andreocchi L, et al. Hypokalaemia in hospitalised patients. Swiss medical weekly. 2016;146(2526):w14320-w.

Moreno-Perez O, Leon-Ramirez J-M, Fuertes-Kenneally L, Perdiguero M, Andres M, Garcia-Navarro M, et al. Hypokalemia as a sensitive biomarker of disease severity and the requirement for invasive mechanical ventilation requirement in COVID-19 pneumonia: a case series of 306 Mediterranean patients. International Journal of Infectious Diseases. 2020;100:449-54.

Nasomsong W, Ungthammakhun C, Phiboonbanakit D, Prapaso S, Luvira V, Changpradub D. Low serum potassium among patients with COVID-19 in Bangkok, Thailand: Coincidence or clinically relevant? Tropical Doctor. 2021;51(2):212-5.

Szoke D, Caruso S, Aloisio E, Pasqualetti S, Dolci A, Panteghini M. Serum potassium concentrations in COVID-19. Clinica Chimica Acta. 2021;512:26-7.

Tsiberkin A, Klyaus N, Sazonova YV, Semenov A. Hypokalemia in hospitalized patients with pneumonia associated with COVID-19. " Arterial’naya Gipertenziya"(" Arterial Hypertension"). 2020;26(4):462-7.

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Published

2023-11-01