ABSTRACT
Background/Objectives: Runaway inflammation is a key feature of COVID-19. NR3C1 gene encodes for glucocorticoid receptor which plays an important role in inflammation reaction. The variant rs41423247 cause increased glucocorticoid receptors sensitivity. This study aimed to investigate the impact of variants of NR3C1 gene on the course of COVID-19 pneumonia in patients with necessarily artificial lung ventilation. Method(s): The study group included 20 patients (9 women and 11 men) with diagnosis viral COVID-19 pneumonia on artificial lung ventilation at the intensive care unit. All patients underwent daily standard examinations according clinical protocols. Determination of NR3C1 gene variants was carried out by using PCRRFLP. Result(s): There were found the significant negative correlations between NR3C1 gene variants and level of SpO2 (rS = -0.601, p = 0.008), Glasgow Coma Scale score (rS = -0.523, p = 0.026). Also, it was defined a protective effect of genotype CC at risk of development acute respiratory distress syndrome in this patients (chi2 = 4.38, p = 0.037, OR = 0.05 (CI:0.01-0.66)). Conclusion(s): The investigated variant rs41423247 of the NR3C1 gene may be the genetic predictor of complicated course of COVID-19 pneumonia. .
ABSTRACT
Introduction: It is known that the development of COVID-19 in the human body consists of complex system of biological mechanisms underlying the complex interplay between infectious agents and the human host. This raised the question about hosts' genetic variants as predictors of clinical phenotype. The aim of our study was to analyze the effect of the NOS3 gene (VNTR intron 4 a/b), NR3C1 gene (C647G, rs41423247) and the SFTPB gene (C1580T, rs11130866) variants on the course of severe COVID-19 pneumonia in patients. Material(s) and Method(s): The study group included 20 patients (13 men and 7 women) with diagnosis "viral COVID19 pneumonia" treated at the intensive care unit. Investigation of the NOS3, NR3C1 and SFTPB genes variants was carried out by a molecular method using PCR-RFLP and allele-specific PCR, respectively. Result(s): The correlation analysis showed a significant association of the NOS3 gene variants and level of SpO2 (rS=-0.488, p=0.029;SpO2=93.1+/-2.4% for b/b and SpO2=82.0+/-1.1% for a/a genotypes). Also a significant positive correlation was between NR3C1 gene variants and duration of nasal intermittent positive pressure ventilation (nIPP) therapy (rS=0.454, p=0.044;for 647CC - 1.5+/-1.0 days and for 674GG - 3.9+/-2.5 days), presence of fever (need for antipyretics) (rS=0.525, p=0.017;647C vs 647G alleles - chi2=5.8, p=0.016). No significant correlations were found for the variants of SFTPB gene. The obtained results support a hypothesis about the combined influence of different pathways genes variants (NOS3 and NR3C1) on severity of COVID-19. However, in order to draw definite conclusions, further multifaceted research in this area are need.