Correlations between Cytokine Levels, Liver Function markers, and Neuropilin-1 Expression in Patients with COVID-19

Abstract

AimThe study evaluated the correlations between cytokine levels, liver function markers, and neuropilin-1 (NRP-1) expression in patients with COVID-19 at Egypt. The study also aimed to evaluate the accuracysensitivity, specificity, and area under the curve (AUC) of the tested laboratory parameters in identifying COVID-19 infection and its severity. Patients and MethodsFifty healthy subjects and 100 confirmed patients with COVID-19 were included in this study. COVID-19 patients were separated into two groups into two groups based on the severity of their symptoms. Serum ALT, AST, albumin, C-reactive protein (CRP), interleukin (IL)-1β, IL-4, IL-6, IL-18, IL-35, prostaglandin E2 (PGE2), and thromboxane A2 (TXA2) were estimated. We measured the gene expression for nuclear factor-kappa B p50 (NF-κB p50) and nuclear factor-kappa B p65 (NF-κB p65) and NRP-1 in the blood samples using quantitative real-time polymerase chain reaction (qRT-PCR). AUC and sensitivity and specificity for cytokine levels and NF-κB p50 and NF-κB p65 and NRP-1 in identifying COVID-19 infection were also determined in both moderate and severe patient groups using receiver-operating characteristic (ROC) curve analysis.ResultsAll patients with COVID-19 showed higher serum activities of liver enzymes, levels of CRP, IL-1β, IL-4, IL-6, IL-18, IL-35 PGE2, TXA2 and mRNA expression of NF-κB p50, NF-κB p65, and NRP-1 than healthy subjects. The severe group exhibited a significant increase in serum ALT, AST and IL-6 and a significant decrease in albumin, IL-1β, TXA2, and NF-κB p65 levels compared to the moderate group. In all patients (moderate and severe), all cytokines were positively correlated with NF-κB p50, NF-κB p65 and NRP-1 expression levels. Serum ALT and AST were positively correlated with CRP, cytokines (IL-4, IL-6, IL-18, IL-35 and TXA2), and NF-κB p50 and NF-κB p65 expression levels in both moderate and severe groups. They were also positively correlated with serum IL-1β level in severe COVID-19 patient group and with NRP-1 expression in moderate group. ROC curve analysis revealed that serum TXA2 level could be useful biomarker for early COVID-19 diagnosis AUC = 0.843 with a sensitivity of 88.0% and a specificity of 75.0% while serum IL-6 level may be a good biomarker to severity COVID-19 since AUC = 0.844 with a sensitivity of 100.00% and a specificity of 68.0%.ConclusionsThis study concluded that liver injury in patients with COVID-19 may be strongly attributed to the cytokines storm, especially IL-6, which was positively correlated to NF-κB p50, NF-κB p65 and NRP-1 mRNA expression levels. Moreover, serum TXA2 level could be useful indicator for early COVID-19 diagnosis and serum IL-6 level could be a reliable biomarker for COVID-19 severity.