Evaluating IL6/D-dimer serum levels and genotypes of rs5186 (A1166C) in AGTR1 angiotensin II receptor type 1 gene as prognostic biomarkers for COVID-19 disease outcome in the Iraqi population

Abstract

Background: On January 30, 2020, the World Health Organization (WHO) declared the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, also called coronavirus disease 2019 (COVID-19) a pandemic after its emergence in Wuhan, China, in December 2019. In this study, we aimed to evaluate the potential of interleukin-6 (IL-6) and D-dimer serum levels and genotypes of rs5186 (A1166C) in the AGTR1 gene as potential prognostic markers for COVID-19 disease outcome in Iraq. Methods: This cross-sectional study was conducted with 100 Iraqi adults of both sexes, aged 21–81 years, and recently diagnosed with COVID-19. The participants of this study were admitted to Al-Al-Kindy Teaching Hospital and Ibn Al-Qiph in Baghdad City from February 01, 2020, to May 01, 2020. Patients with COVID-19 were divided into two categories; those who recovered and were discharged and those who were admitted to the intensive care unit (ICU)/died. Ethical concerns were considered in accordance with the consent form provided by the Iraqi Ministry of Health for the purpose of collecting samples. Interleukin-6 (IL-6) levels in the patients’ serum samples were estimated using the Sandwich-Enzyme Linked Sorbent Assay (ELISA) method with horseradish peroxidase (HRP) conjugated antibody specific for IL-6. D-dimer was estimated in the serum samples using antigen-antibody (anti-human D-dimer antibodies) reaction. Genotyping of rs5186 (A1166C) in the AGTR1 angiotensin II receptor type 1 gene in the cohort study was determined using an allele-specific PCR approach. Results: D-dimer serum levels (1.55 μg/mL) was significantly (P < 0.001) higher in patients admitted to the ICU or those who died compared with those (0.2 μg/mL) of patients who recovered and were discharged. The IL-6 levels in patients admitted to the ICU or those who died and in patients who recovered and were discharged were 12.31 and 11.65 pg/mL, respectively, without significant difference (P > 0.05). The frequency of AC+CC genotypes of rs5186 (A1166C) in the AGTR1 gene in patients who were admitted to the ICU or those who died was 30.43%, higher than that of patients who recovered and were discharged (11.69%) with a significant difference (Odds ratio [OR] = 3.31, 95% confidence interval [CI] = 1.07–10.21, P = 0.038). Analysis of allele distribution revealed a higher frequency of the A allele among patients who recovered and were discharged (93.51% versus 82.61%) than among those who were admitted to the ICU or those who died with a significant difference (OR = 3.03, 95% CI = 1.12–8.21, P = 0.029). Conclusion: D-dimer may be a prognostic biomarker for poor COVID-19 disease outcomes. The genotype AC+CC of rs5186 (A1166C) in the AGTR1 gene seems to be a risk factor and may be a prognostic factor for poor COVID-19 disease outcomes. However, a bigger sample size is highly recommended in prospective studies for better assessment of the potential of IL-6, D-dimer, and genotyping of rs5186 (A1166C) in the AGTR1 gene as prognostic biomarkers for COVID-19 disease outcome.