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The Genetic Association of Single Nucleotide Polymorphisms of SERPINE1 (rs6092) and IFNAR2 (rs1051393, rs2229207) Genes Is Related to Post Covid-19 Respiratory Syndrome

Year: 2025

Type: article

Abstract: Background Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, is a global pandemic. Severe cases may develop post-COVID-19 respiratory syndrome, characterized by symptoms persisting ≥4 weeks. In this study, we aim to identify the association of post-COVID-19 respiratory syndromes with variants in the SERPINE1 and IFNAR2 genes which are responsible for regulating fibrinolysis and immune response against viral infection, respectively. Methods We recalled 85 COVID-19 positive subjects who were originally admitted to Persahabatan Central General Hospital, Jakarta, in 2020—2021. We performed TaqMan genotyping on clinically relevant variants at rs1051393 and rs2229207 in IFNAR2 and rs6092 in SERPINE1 and conducted statistical analysis to identify the association of these variants with the clinical manifestations of post-COVID-19 respiratory syndrome. Results We found that patients with post-COVID-19 respiratory syndrome had greater disease severity at admission (p = 0.02) and during hospitalization (p = 0.004), along with longer hospital stays (p = 0.0001), possibly due to poorer radiological findings at admission (p = 0.013) and discharge (p = 0.001). Variants in SERPINE1 and IFNAR2 showed significant associations: rs1051393 ( IFNAR2 ) with fever (p = 0.037), and rs2229207 with chest pain (p = 0.047), higher potassium (p = 0.001), chloride (p = 0.047), and pCO 2 (p = 0.030). Additionally, rs6092 ( SERPINE1 ) was linked to increased basophils (p = 0.027) and eGFR (p = 0.036). After Benjamini–Hochberg correction, only disease severity during hospitalization (padj = 0.021), radiological findings at admission (padj = 0.052) and discharge (padj = 0.008), hospitalization duration (padj = 0.00016), and the association of rs2229207 with potassium levels (padj = 0.003) remained significant. Conclusion Our findings suggested the potential contribution of genetic predispositions in the SERPINE1 and IFNAR2 genes to the emergence of post-COVID-19 respiratory symptoms, providing additional consideration in treatment management to improve the outcomes of patients positive for COVID-19.

Source: F1000Research

DOI: 10.12688/f1000research.167074.1