Immunogenetic and molecular biomarkers in COVID-19 and hepatitis C virus infection: Evaluating the diagnostic potential of HLA (rs1131500), IGF-2, and I-FABP

Figure 1 Box plots showing the distribution of clinical parameters (age, body mass index, Hp, erythrocyte sedimentation rate at 1 h and 2 h, O₂ saturation, international normalized ratio, and lactate dehydrogenase) across different patient groups. The median, interquartile range, and potential outliers are displayed for each parameter, allowing comparison between groups. HCV: Hepatitis C virus; COVID-19: Coronavirus disease 2019; BMI: Body mass index; LDH: Lactate dehydrogenase; INR: International normalized ratio.

Figure 2 Heatmap showing the expression profiles of pro-inflammatory cytokines (insulin-like growth factor 2 [IGF-2], intestinal fatty-acid-binding protein [I-FABP], and interferon-gamma IFN-γ]) in A: Dual hepatitis C virus-coronavirus disease 2019 group; B: Coronavirus disease 2019 group; and C: Hepatitis C virus group. Each row represents an individual patient sample, and each column represents a cytokine. Color intensity reflects relative expression levels, with red indicating higher expression and blue indicating lower expression. Hierarchical clustering was applied to both samples and cytokines to highlight patterns and similarities in cytokine expression across the cohort. IFN: Interferon; IGF: Insulin-like growth factor; I-FABP: Intestinal fatty-acid-binding protein.

Figure 3 Heatmaps representing Pearson correlation coefficients among insulin-like growth factor 2, intestinal fatty-acid-binding protein, and interferon-gamma (all measured in ng/L) in the hepatitis C virus-coronavirus disease 2019 coinfected group, coronavirus disease 2019 group, and hepatitis C virus group. Each cell shows the strength and direction of the correlation between pairs of biomarkers, with color intensity indicating correlation magnitude (blue: Negative, red: Positive). While most correlations were weak and not statistically significant, a borderline significant positive correlation was observed between intestinal fatty-acid-binding protein and interferon-γ in the coronavirus disease-2019 group (r = 0.261, P = 0.050). HCV: Hepatitis C virus; COVID-19: Coronavirus disease 2019; IFN: Interferon; IGF: Insulin-like growth factor; I-FABP: Intestinal fatty-acid-binding protein.

Figure 4 Correlation between intestinal fatty-acid-binding protein and interferon-gamma in the coronavirus disease 2019 group. COVID-19: Coronavirus disease 2019; IFN: Interferon; I-FABP: Intestinal fatty-acid-binding protein.

Figure 5 Receiver operating characteristic curves of insulin-like growth factor 2, intestinal fatty-acid-binding protein, and interferon-gamma for evaluating the sensitivity and specificity of insulin-like growth factor 2, intestinal fatty-acid-binding protein, and interferon-gamma in diagnosing infection. The curves illustrate the diagnostic performance of each biomarker, with the area under the curve (AUC) values shown in the figure. Insulin-like growth factor 2 demonstrated excellent discrimination (AUC = 0.996), while I-FABP and interferon-gamma showed more modest performance (AUC = 0.736 and 0.684, respectively). The diagonal line represents the line of no discrimination (AUC = 0.5). Sensitivity and specificity are plotted across different thresholds. HCV: Hepatitis C virus; COVID-19: Coronavirus disease 2019; IFN: Interferon; IGF: Insulin-like growth factor; I-FABP: Intestinal fatty-acid-binding protein.

Figure 6 Distribution of CC, CT, and TT genotypes across the four study groups (hepatitis C virus-coronavirus disease 2019, coronavirus disease 2019, hepatitis C virus, and Control). This distribution suggests potential differences in genotype association with hepatitis C virus, coronavirus disease 2019, and co-infection. HCV: Hepatitis C virus; COVID-19: Coronavirus disease 2019.