Derya KORKMAZ, Tülay KÖKEN, Halit Buğra KOCA, Semiha ORHAN, Neşe DEMİRTÜRK

The relationship between serum soluble ACE 2 protein level and the clinical course of COVID-19 disease

Aims: The angiotensin converting enzyme 2 (ACE 2) molecule, which mediates the entry of the virus into the cell, plays a very important role in the pathogenesis of COVID-19 disease. However, its effect on prognosis has not been fully explained. In this study, it was aimed to investigate the relationship between soluble ACE 2 (sACE 2) levels in the blood and the course of the disease. Methods: sACE 2 levels at 0, 3 and 5 days were measured in patients with mild, moderate and severe COVID-19 pneumonia who were hospitalized between March 15, 2020 and August 30, 2020. Results: 69 patients, 35 (51.5%) female and 34 (49.3%) male, with a mean age of 64.3±2.1 were included in the study. 42.0% of the patients had mild, 30.4% moderate, 27.5% severe pneumonia. Clinical follow-up of 7 patients resulted in death. There was no statistically significant difference between sACE 2 levels and gender, severity of pneumonia, initial hospitalization, presence of intubation and mortality. Conclusion: sACE 2 levels were not associated with disease severity and inflammatory markers. Studies in larger patient populations are needed to explain the relationship between sACE 2 activity and SARS-CoV-2 infection and to develop new treatment strategies.

Keywords:

COVID-19, angiotensin converting enzyme 2, prognosis,

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Pascarella G, Strumia A, Piliego C, et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med. 2020;288(2):192-206.
Qiu P, Zhou Y, Wang F, et al. Clinical characteristics, laboratory outcome characteristics, comorbidities, and complications of related COVID-19 deceased: a systematic review and meta-analysis. Aging Clin Exp Res. 2020;32(9):1869-1878.
Li J, Huang DQ, Zou B, et al. Epidemiology of COVID-19: a systematic review and meta-analysis of clinical characteristics, risk factors, and outcomes. J Med Virol. 2021;93(3):1449-1458.
Wang J, Zhao H, An Y. ACE2 shedding and the role in COVID-19. Front Cell Infect Microbiol. 2022;11:789180.
Gheblawi M, Wang K, Viveiros A, et al. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ Res. 2020;126(10):1456-474.
Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(8):1-5.
Almehdi AM, Khoder G, Alchakee AS, Alsayyid AT, Sarg NH, Soliman SSM. SARS-CoV-2 spike protein: pathogenesis, vaccines, and potential therapies. Infection. 2021;49(5):855-876.
Mousavizadeh L, Ghasemi S. Genotype and phenotype of COVID-19: Their roles in pathogenesis. J Microbiol Immunol Infect. 2021;54(2):159-163.
Bayati A, Kumar R, Francis V, McPherson PS. SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis. J Biol Chem. 2021;296:100306.
Zhang J, Xiao T, Cai Y, Chen B. Structure of SARS-CoV-2 spike protein. Curr Opin Virol. 2021;50:173-82.
Watanabe Y, Allen JD, Wrapp D, McLellan JS, Crispin M. Site-specific glycan analysis of the SARS-CoV-2 spike. Science. 2020;369:330-333.
Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020;76:14-20.
Xiao L, Sakagami H, Miwa N. ACE2: the key molecule for understanding the pathophysiology of severe and critical conditions of COVID-19: demon or angel? Viruses. 2020;12(5):491.
Cheng H, Wang Y, Wang GQ. Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19. J Med Virol. 2020;92(7):726-730.
Rice GI, Jones AL, Grant PJ, Carter AM, Turner AJ, Hooper NM. Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family study. Hypertension. 2006;48(5):914-920.
British Society of Thoracic Imaging. Thoracic Imaging in COVID-19 Infection. Guidance for the Reporting Radiologist. Ver sion 2. 16th March 2020. UK: BSTI. Avaliable at: https://www.bsti.org.uk/media/resources/files/BSTI_COVID-19_Radiology_Guidance_versio.
Karthika T, Joseph J, Akshay Das VR, et al. SARS-CoV-2 cellular entry is independent of the ACE2 cytoplasmic domain signaling. Cells. 2021;10(7):1814.
Yeung ML, Teng JLL, Jia L, et al. Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system. Cell. 2021;184:2212-2228.e12.
Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell. 2020;181(4):905-913.e7.
Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020;17(5):259-260.
Mohammadi P, Varpaei HA, Seifi A, et al. Soluble ACE2 as a risk or prognostic factor in COVID-19 patients: a cross-sectional study. Med J Islam Repub Iran. 2022;36:135.
Robertson J, Nellgård B, Hultén LM, et al. Sex difference in circulating soluble form of ACE2 protein in moderate and severe COVID-19 and healthy controls. Front Med. 2022;9:1058120.
Avanoglu Guler A, Tombul N, Aysert Yıldız P, et al. The assessment of serum ACE activity in COVID-19 and its association with clinical features and severity of the disease. Scand J Clin Lab Invest. 2021;81(2):160-165.