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. 2023 Jul;50(7):5827-5836.
doi: 10.1007/s11033-023-08515-0. Epub 2023 May 24.

Angiotensin converting enzyme 2 gene expression and markers of oxidative stress are correlated with disease severity in patients with COVID-19

Afraa S H Alobaidy  1 , Mona Elhelaly  2 , Maggie E Amer  1 , Rasha S Shemies  3 , Azza I Othman  1 , Mohamed A El-Missiry  4
Affiliations

Angiotensin converting enzyme 2 gene expression and markers of oxidative stress are correlated with disease severity in patients with COVID-19

Afraa S H Alobaidy et al. Mol Biol Rep. 2023 Jul.

Abstract

Background: Oxidative stress is thought to play a significant role in the pathogenesis and severity of COVID-19. Additionally, angiotensin converting enzyme 2 (ACE2) expression may predict the severity and clinical course of COVID-19. Accordingly, the aim of the present study was to evaluate the association of oxidative stress and ACE2 expression with the clinical severity in patients with COVID-19.

Methods and results: The present study comprised 40 patients with COVID-19 and 40 matched healthy controls, recruited between September 2021 and March 2022. ACE 2 expression levels were measured using Hera plus SYBR Green qPCR kits with GAPDH used as an internal control. Serum melatonin (MLT) levels, serum malondialdehyde (MDA) levels, and total antioxidant capacity (TAC) were estimated using ELISA. The correlations between the levels of the studied markers and clinical indicators of disease severity were evaluated. Significantly, lower expression of ACE2 was observed in COVID-19 patients compared to controls. Patients with COVID-19 had lower serum levels of TAC and MLT but higher serum levels of MDA compared to normal controls. Serum MDA levels were correlated with diastolic blood pressure (DBP), Glasgow coma scale (GCS) scores, and serum potassium levels. Serum MLT levels were positively correlated with DBP, mean arterial pressure (MAP), respiratory rate, and serum potassium levels. TAC was correlated with GCS, mean platelet volume, and serum creatinine levels. Serum MLT levels were significantly lower in patients treated with remdesivir and inotropes. Receiver operating characteristic curve analysis demonstrates that all markers had utility in discriminating COVID-19 patients from healthy controls.

Conclusions: Increased oxidative stress and increased ACE2 expression were correlated with disease severity and poor outcomes in hospitalized patients with COVID-19 in the present study. Melatonin supplementation may provide a utility as an adjuvant therapy in decreasing disease severity and death in COVID-19 patients.

Keywords: Angiotensin converting enzyme 2 gene; COVID-19; Malondialdehyde; Melatonin; SARS-CoV-2; Total antioxidant capacity.

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Conflict of interest statement

The authors declare that they have no conflict of interest to declare.

Figures

Fig. 1
Fig. 1
ACE2 expression levels. Median ACE2 (FC), 0.05; 95% CI, 0.0.017 to 0.098; Hodges–Lehmann location estimator, 0.0766; P < 0.001)
Fig. 2
Fig. 2
Diagnostic performance of serum ACE2 and oxidative markers. ROC curve analysis of serum ACE2 and oxidative markers for the ability to discriminate between patients with COVID-19 (n = 40) and healthy controls (n = 40). AUC, area under the ROC curve; CI, confidence interval; SE, standard error
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