Association of the C3953T (rs1143634) variant of the interleukin 1 beta gene with the features of a complicated course of COVID-19-associated pneumonia.

BACKGROUND: The pro-inflammatory cytokine IL-1 plays an important role in severe COVID-19. A change in IL-1 production may be associated with a mutation in the IL1Β gene. Our study analyzed the impact of the IL1Β gene variants (rs1143634) on disease progression in patients with severe COVID-19 pneumonia, taking into account treatment strategies. METHODS AND RESULTS: The study enrolled 117 patients with severe COVID-19 pneumonia. The IL1Β gene variants were identified using the polymerase chain reaction-restriction fragment length polymorphism method. In the group of patients, the following genotype frequencies were found based on the investigated rs1143634 variant of the IL1Β gene: CC-65.8%, CT-28.2%, and TT-6.0%. Our results showed that the group of patients with the T allele of the IL1Β gene had higher leukocyte counts (p = 0.040) and more pronounced lymphopenia (p = 0.007). It was determined that patients carrying the T allele stayed on ventilators significantly longer (p = 0.049) and required longer treatment with corticosteroids (p = 0.045). CONCLUSION: Identifying variants of the IL1Β gene can be used as a predictive tool for assessing the severity of COVID-19 pneumonia and tailoring personalized treatment strategies. Further research with a larger patient cohort is required to validate these findings.

NOS3 (rs61722009) gene variants testing in prediction of COVID-19 pneumonia severity.

BACKGROUND: There is a hypothesis that a sufficient level of endothelial nitric oxide synthase is important for reliable protection against COVID-19. Theoretical ideas about the NOS3 gene demonstrated that it can have an effect on links of the complications pathogenesis in COVID-associated pneumonia. We determined the goal - to investigate the association of the NOS3 gene variants with the occurrence of the disease and its clinical course in patients of the intensive care unit. METHODS: The study group included 117 patients with a diagnosis of severe "viral COVID-19 pneumonia". Determination of NOS3 gene variants was performed using the PCR method. The probability of differences in the quantitative results were determined using ANOVA or Kruskal-Wallis test (depend of normality of studied parameters). RESULTS: Our results indicate that the presence of the NOS3 gene 4a allele increase the risk of complicated COVID-19-associated pneumonia (χ2 = 18.84, p = 0.00001, OR = 3.53 (1.95-6.39)). It was showed, that carriers of the 4aa genotype had a significantly higher ratio of SpO2/FiO2 on the first and second days after hospitalization (p = 0.017 and p = 0.03, respectively). Patients with the 4aa genotype also had the acid-base imbalances, as showed by indicators of base deficiency and standard bicarbonate, which were beyond the reference values. Potassium and sodium concentrations on the first and second day after hospitalization were also significantly lower in patients with 4aa genotype (p = 0.009 and p = 0.048, respectively), for whom, in the same time, the concentrations of C-reactive protein and total bilirubin were significantly higher (p = 0.002 and p = 0.033, respectively). CONCLUSIONS: Our results confirmed that the rs61722009 variant of the NOS3 gene is associated with an increased risk of severe СOVID-19-associated pneumonia and its adverse clinical course with potential progression of kidney and liver damage, and occurrence risk of systemic inflammatory response syndrome. These results require further research for the new metabolic strategy formation, in order to prevent the severe COVID-19 associated pneumonia and its complications.

SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants as potential clinical biomarkers for personalized treatment strategy selection in patients with severe COVID-19 pneumonia.

BACKGROUND: Exploring the pathogenetic mechanisms behind severe lung damage in COVID-19 is crucial. In this study, we decided to focus on two molecular markers that affect surfactant metabolism and lung development: the surfactant protein B (SFTPB) and the glucocorticoid receptor (NR3C1) genes. The aim of our study was to determine the effect of SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants on the course of the disease in patients with COVID-19, and the treatment measures they required. METHODS: The study group included 58 patients with a diagnosis of severe "viral COVID-19 pneumonia." Determination of SFTPB and NR3C1 gene variants was performed using the PCR-RFLP method. RESULTS: Our results indicate that the presence of the SFTPB gene CC genotype increases the risk of developing acute respiratory distress syndrome in patients with COVID-19 (χ2 = 4.03, p = 0.045, OR = 3.90 [1.19-12.78]). However, patients with the SFTPB gene TT genotype required respiratory support for a shorter period of time. Patients with the NR3C1 gene CC genotype underwent a longer glucocorticoid therapy. Moreover, for patients with the CC genotype, a longer stay in the intensive care unit was detected before lethal outcome. CONCLUSIONS: The obtained results confirm the influence of the SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants on the therapy, course, and severity of the disease in patients with COVID-19. Of course, these results require further study, analysis, and larger, complex, systematic research.

Modifying effects of TNF-α, IL-6 and VDR genes on the development risk and the course of COVID-19. Pilot study.

OBJECTIVES: COVID-19 continues to range around the world and set morbidity and mortality antirecords. Determining the role of genetic factors in the development of COVID-19 may contribute to the understanding of the pathogenetic mechanisms that lead to the development of complications and fatalities in this disease. The aim of our study was to analyze the effect of TNF-α (rs1800629), IL-6 (rs1800795) and VDR (rs731236 and rs1544410) genes variants on the development risk and the course of COVID-19 in intensive care patients. METHODS: The study group included 31 patients with diagnosis "viral COVID-19 pneumonia". All patients underwent standard daily repeated clinical, instrumental and laboratory examinations. Determination of IL-6, TNF-α, and VDR genes variants was performed using the PCR-RFLP method. RESULTS: It was found a significant increase in the rate of the CC genotype and C allele (38.7 vs. 12.0% and 0.6 vs. 0.4%, respectively) of the IL-6 gene in all patients of the study in comparison with population frequencies. There was a significantly higher rate of heterozygous genotypes TC and GA of the VDR gene in group of died patients. The rs1800629 variant of the TNF-α gene is associated with the need for respiratory support and its longer duration in patients with COVID-19. CONCLUSIONS: The obtained results support a hypothesis about the influence of variants of IL-6, TNF-α and VDR genes on severity of COVID-19. However, in order to draw definite conclusions, further multifaceted research in this area are need.

ELECTROCARDIOGRAPHIC CHANGES IN NEWBORNS FROM MOTHERS WITH METABOLIC SYNDROME.

OBJECTIVE: The aim: Analysis of electrocardiographic parameters in newborns from mothers with metabolic syndrome. PATIENTS AND METHODS: Materials and methods: We conducted a prospective cohort trial of 125 newborns, which included the study of their anthropometric, clinical and laboratory indicators and, in particular, ECG parameters. The main group consisted of 40 children, born from mothers with diagnosed metabolic syndrome, the comparison group included 2 subgroups: 28 term newborn and 57 preterm, from mothers without metabolic syndrome. RESULTS: Results: In newborns from mothers with metabolic syndrome on a fragmentary ECG we revealed abnormal depolarization, manifested by changes in the ventricular complex -QRS expansion (p<0.001), impaired conduction (p = 0.004), changes of T wave (p<0.001) and prolonged QT interval (p<0.001). There are such risk factors for QT prolongation in neonates: disease cardiovascular system and disorders of lipid metabolism in mother, asphyxia at birth and electrolyte disorders (hypernatremia OR 0.97), weight too high to gestational age at birth in newborn (OR 2.97), increased blood pressure in the neonatal period (OR 1.07), artificial feeding (OR 3.01). CONCLUSION: Conclusions: Metabolic syndrome in women during pregnancy has a pronounced effect on the cardiovascular system of the newborn. The detected signs of cardiac dysfunction on the ECG can serve as early integrated indicators of metabolic syndrome and cardiovascular disease in children.

CLINICAL PREDICTION OF EARLY ONSET SEPSIS IN PRETERM NEONATES.

OBJECTIVE: The aim of the study was to analyze and identify risk factors for the development of early onset sepsis in preterm neonates and to develop a clinical prognostic model. PATIENTS AND METHODS: Materials and methods: A retrospective cohort study included 152 newborns with birth weight from 1000 to 2500 g, who were treated in the neonatal intensive care units of medical institutions in the Poltava region. Among 152 children, 121 had clinical and laboratory symptoms of infection, which were regarded as manifestations of early onset sepsis, the rest of the children (n = 31) had no manifestations of infection. RESULTS: Results: According to the results of multiple stepwise logistic regression analysis, the predictive model has been developed. It included gestational age, visual changes of placenta, Apgar score at the 1st minute, the level of monocytes more than 6.5%, the history of abortions and premature rupture of membranes. The diagnostic characteristics of the developed model had high: sensitivity - 82.2%, specificity - 93.55%, positive predictive value - 97.98%, negative predictive value - 58%. CONCLUSION: Conclusions: The prognostic model developed by us, which showed high diagnostic characteristics, includes information on maternal risk factors, the state of the newborn immediately after birth, and biomarkers of infection (C-reactive protein and monocyte count). Therefore, we believe that when interpreting biomarkers, the decision to prescribe antibiotics should be based on the presence of maternal risk factors and clinical symptoms of infection in the prematurely born child, which may be nonspecific.

Effect of enos gene polymorphism on the course of early onset bacterial infections in premature infants.

OBJECTIVE: The aim of the study was to analyze the associations between 4a/4b polymorphism of the eNOS gene and impaired systemic hemodynamics in premature infants with early neonatal sepsis. PATIENTS AND METHODS: Materials and methods: We conducted a prospective cohort study, which included 120 premature babies with early neonatal sepsis, in 57 children the course of the disease was accompanied by arterial hypotension (AH) and in 61 children - not. In children of both groups, genotyping was performed to determine 4a/4b polymorphism of the eNOS gene. RESULTS: Results: It was shown that the heart rate, blood pressure, hourly diuresis, the level of total nitrates and nitrites in the urine, as well as a number of echocardioscopic and dopplerometric indicators in children with different eNOS gene genotypes are not different. CONCLUSION: Conclusions: There is no effect of 4a/4b polymorphism of the eNOS gene on the occurrence of hemodynamic disturbances in premature infants with sepsis.

Development of arterial hypotension in premature infants with early onset bacterial infections: tools of clinical predication.

OBJECTIVE: Introduction: The safe thresholds of blood pressure in preterm neonates are still unclear. The aim of our study was to substantiate the diagnostic criteria for the syndrome of arterial hypotension (AH) and indications for the appointment of hemodynamic support in premature infants with early onset bacterial infections. PATIENTS AND METHODS: Materials and methods: A prospective cohort study was conducted. 2 experimental groups were formed -premature babies with early onset bacterial infections and AH (n = 58), and control group (n = 62), premature babies without AH. The subjects of the study were a number of risk factors. Simple and multiple logistic regression analyses were used. RESULTS: Results: In premature infants with AH, compared with those without AH, there are significantly lower values of stroke index of left ventricle (SILV), index of resistance (IR) of the middle cerebral artery, pH, significantly higher level of urea in serum and a higher proportion of children with hypoglycemia. Multiple logistic regression analysis was used to develop a clinical prognostic model for the AH-syndrome. Only prognostic model, which included SILV, blood pH and blood glucose, had high prognostic characteristics and the largest area under the ROC curve. CONCLUSION: Conclusions: The following diagnostic criteria can be used for the appointment of medical support for hemodynamics: the digital value of the level of mean blood pressure, expressed in mmHg, is less than the gestational age in weeks, and at least one of the following indicators -pH is less than 7.2, blood glucose level is less than 2.8 mmol/l, SILV is less than the normal ranges.

[Predicting the occurrence of severe intraventricular hemorrhages and ways to prevent their development in preterm infants].

OBJECTIVE: Introduction: Severe intraventricular hemorrhages (IVH) in preterm infants are one of the major public health problems, as they can cause neurological and cognitive impairment, as well as lethal outcomes. The aim: To prevent the development of IVH in preterm infants by developing an algorithm for identification of high risk infants and a bundle for the prediction and prevention of this pathology. PATIENTS AND METHODS: Materials and methods: A multicenter study (2013-2016) was conducted, which included 117 premature babies who were on treatment in 4 medical institutions in the Poltava region (Ukraine). The group of children with severe IVH included 76 children (weight 1037.8 ± 43.7 g, gestational age (GA) 27.1 ± 0.27 weeks; girls 36/47, 37 %), with IVH III-IV st. by Papile L.A. The comparison group consisted of 41 children (weight 1758 ± 59.8, GA 32.1 ± 0.30 weeks, girls 15/38, 46 %) without IVH. The effectiveness of a bundle for the prediction and prevention severe IVH was studied in the Poltava Regional Perinatal Center (high level, 2000 births per year) during 2014 - 2017. RESULTS: Results: The significant risk factors due to multiple regression logistic analysis are: gestational age (OR =0.28, р=0.000), anhydrous period less than 24 hours (OR =83,29; р=0.020), infusion of 0.9% sodium chloride solution during primary resuscitation (OR =16.73; р=0.042), episodes of arterial hypertension (OR =32.3; р=0.026), the number of leukocytes is ≥15x109/l at birth (OR=17.6; р=0.028). After the implementation of the Bundle, which included: an interdisciplinary check-list (between the obstetrician and the neonatologist), the algorithm for identifying children with high risk of IVH, a check-list for monitoring of the state of the child immediately after birth and an interprofessional check-list (between the doctor and the nurse), the IVH incidence decreased from 18.9 % to 11.4 %, p = 0.038, and the disability from 9.6 % to 2.4 %, p = 0.046. CONCLUSION: Conclusions: The Bundle is an effective tool for preventing of severe IVH in preterm infants.