RESUMEN
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. .
RESUMEN
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.
RESUMEN
Nearly 6.5 million people have died worldwide from the COVID-19 pandemic. Improvement of pediatric patients survival depends on the continued provision of basic health services to women and children all over the world. The world scientific community must start more scientific clinical investigations and receive more data in order to know the impact of COVID-19 on children's health and mortality, and to ensure that children and adolescents do not die from preventable events. Such trends in the spread of morbidity and mortality from COVID-19 require an interdisciplinary approach as soon as possible to further contain the spread of the disease and prevent complications in order to improve the quality of life. Insufficiently studied molecular changes in lung morpho-biology due to the action of COVID-19 complicate its clinical treatment. An in-depth genetic mechanisms investigation during pathogenetic disorders caused by virus can help in the development of new treatment methods, in particular, the use of surfactant drugs as a component of basic therapy. Recently, it became known that COVID-19-associated lung damage is characterized by typical pathophysiological changes for RDS. Diffuse alveolar damage occurs due to edema of the interstitium, the formation of hyaline membranes, as well as the proliferation of fibroblasts at the stage of recovery. When COVID-19 affects the lungs, surfactant synthesis is dysregulated, as viral proteins suppress the expression of regulatory genes. Changes during the reparation process also lead to loss of surfactant function. Surfactant replacement therapy can be an alternative in the treatment of patients with COVID-19associated lung damage, there are a number of studies that prove the effectiveness of such therapy in other infections. COVID-19 can be especially dangerous for children with chronic lung disease, congenital malformations, previously undiagnosed genetic defects in the surfactant production system. However, timely use of surfactant replacement therapy can prevent one of the worst complications during mechanical ventilation - air leakage syndrome. © Yu.I.Chernyavska, V.I. Pokhylko, Z.I. Rossokha, S.M. Tsvirenko, N.I. Hasiuk, 2022.
RESUMEN
Nowadays, the creation of treatment protocols for young children with COVID-19 is especially relevant, as some issues of pathogenesis and genetic determinism of severe lung damage are still unclear. COVID-19-induced respiratory distress syndrome is a predictable severe complication that requires early diagnosis and proper treatment. Given the pathogenetic mechanism of lung damage in COVID-19, surfactant replacement therapy may be useful in the treatment of this cohort of patients. Clinical case. A clinical case of severe coronavirus infection caused by SARS-CoV-2 in a 6-month-old child is presented. The course of the disease was accompanied by severe damage to the lung parenchyma with the development of acute respiratory distress. The examination of the patient confirmed the genetic determinism of severe COVID-19, polymorphic risk alleles of the genes GSTM1, GSTP1, SFTP-B. The child's treatment included not only long-term mechanical ventilation, but also surfactant replacement therapy. The child recovered and was discharged without signs of respiratory failure. Conclusions. This clinical case demonstrates the association of genetic polymorphism with severe virus-induced lung damage. Because severe respiratory failure in COVID-19 is likely to be due to the development of acute respiratory distress syndrome, administration of exogenous surfactant should be considered as a possible treatment option. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. © 2021 Group of Companies Med Expert, LLC. All Rights Reserved.