[Interferon gamma in the treatment of patients with moderate COVID-19].

INTRODUCTION: Interferons are produced in response to the presence of pathogens in cells and are responsible for the proper formation of immune reaction. Preliminary data obtained in studies of properties of recombinant interferon gamma (IFN-γ) that involved patients with community-acquired pneumonia (including bacterial), acute respiratory viral infection (ARVI), influenza and new coronavirus infection have shown promising results.The purpose of the study was to assess the effect of subcutaneous administration of IFN-γ in patients with viral pneumonia on the changes of vital signs and the duration of hospital stay. MATERIAL AND METHODS: An open-label, randomized, low-interventional study included patients with moderate new coronavirus infection COVID-19 over 18 years of age of both sexes. IFN-γ 500,000 IU was administered s/c, daily, once a day, during 5 days. RESULTS: IFN-y in addition to complex therapy of the disease resulted in more favorable changes in the stabilization of vital signs, as well as in reduced length of fever and hospital stay by 2 days what allows suggesting a positive effect of this substance on the recovery processes in patients with moderate COVID-19. Special emphasis should be made to the fact that patients who received recombinant IFN- γ experienced no progression of respiratory failure and required no transfer to intensive care unit. DISCUSSION: This study confirms earlier obtained data on the positive effect of IFN-y on the rate of clinical stabilization and recovery of patients with community-acquired pneumonia and viral infections. Presented results are limited to a small number of patients; further study of drug properties in post-marketing studies is required. CONCLUSION: Progress in the treatment of patients with moderate COVID-19 by adding recombinant IFN-γ to the complex therapy may reasonably expand the range of existing treatment options for this infection.

[Prognostic value of aortic stenosis in patients after acute coronary syndrome].

With the aim to assess prevalence of aortic stenosis (AS) and prognostic value of its detection among survivors of acute coronary syndrome (ACS) we examined 851 patients included into multicenter prospective study of risk factors of serious vascular events and death after acute coronary syndrome. The patients were enrolled into the study in stable condition on 10th day after onset of myocardial infarction (MI) or unstable angina (UA). Examination involved medical history, laboratory tests and echocardiography. Afterwards all cases of death and serious vascular events were registered. Severity of AS was specified by maximal aortic flow rate: 1st degree > 2.5, 2nd degree 3.0-4.0, 3rd degree > 4.0 m/s. AS was detected in 16 patients (1.9%). AS severity was 1st, 2nd and 3rd degree in 9, 4 and 3 patients, respectively. Patients with AS were significantly older (77.4 vs. 61.3 years, p < 0.001), more often had history of chronic heart failure (CHF) (81.3 vs. 53.2%, p = 0.021) and lowered renal function (66.7 vs. 34.0%, p < 0.041). At multifactorial analysis independent prognostic value in relation to development of serious events showed age > 75 years (OR 1,395 [1.023-1.902], p = 0.036), history of CHF (1.319 [1.015-1.713], p = 0.038), history of MI (1.692 [1.320-2.170], p < 0.001), left ventricular diastolic dimention (1.023 [1.005-1.041], p = 0.012), left atrial diameter (1.024 [1.001-1.047], p = 0.037) and presence of AS (3.211 [1.742-.,916], p < 0.001). Prevalence of preexisting AS among patients who have had MI/UA is 1.9% what is similar to data of European Heart Survey ACS-II (1.8%). Presence of AS of any severity in a survivor of ACS worsens prognosis independently of other known risk factors.

[Prognostic value of levels of brain natriuretic peptide and genetic factors in patients after acute coronary syndrome].

Prognostication of the course of disease in patients with high risk of unfavorable outcome of ischemic heart disease (IHD) is of great importance for creation of individualized strategy of treatment. We have investigated contribution of levels of brain natriuretic peptide (BNP) and genetic factors in the risk of development of complications of atherosclerosis in patients who have had acute coronary syndrome. We started to follow 324 patients on day 10 of stable state after acute coronary syndrome (55.1% with Q-wave myocardial infarction, 18.5% with non-Q myocardial infarction, 25.5% with unstable angina, men BNP level 624.5+/-32.13 mol/ml [70.3 - 4276.6]). Duration of followup was 2 years. Baseline BNP level in patients with unfavorable outcome during followup (fatal and nonfatal myocardial infarction and stroke) was 872.47+/-91.42 compared with 592.45+/-35.97 mol/ml in patients without unfavorable outcome (p=0,001). Multifactorial Cox analysis showed that carriage of T allele of polymorphic marker (--1654) of protein C gene, elevated BNP level, symptomatic atherosclerosis of peripheral arteries, history of MI, and use of thiazide diuretics were independently associated with unfavorable outcomes (p=0.026, <0.0001, <0.0001, =0.001, =0.024, respectively). Thus genetic factors and study of BNP allow to improve prediction of unfavorable outcome after exacerbation of IHD.

[Polymorphic markers Ala455Val of the THBD gene and Arg353Gln of the F7 gene and association with unfavorable outcomes of coronary atherosclerosis in patients with a history of acute ischemic heart disease].

The polymorphic markers Ala455Val of the THBD gene and Arg353Gln of the F7 gene were tested for association with the frequency of unfavorable outcomes in patients with a history of acute ischemic heart disease. The study involved 1145 patients hospitalized in cardiology clinics of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol, and Rostov-on-Don because of acute ischemic heart disease. The patients were followed up for up to 62.5 months. None of the markers displayed a significant association with the time to an endpoint. The patients were then grouped by sex. In females, the frequency of unfavorable outcomes (fatal or nonfatal myocardial infarction and fatal or nonfatal stroke) was higher in carriers of allele Val of the Ala344Val polymorphic marker of the THBD gene and carriers of genotype Arg/Arg of the Arg353Gln polymorphic marker of the F7 gene, but the difference was not statistically significant. Such an increase in frequency was not observed in males. To study the combined effect of the polymorphic markers of the THBD and F7 genes, the course of ischemic heart disease was compared for two female subgroups. One included carriers of allele Val of the Ala344Val polymorphic marker of the THBD gene and genotype Arg/Arg of the Arg353Gln polymorphic marker of the F7 gene; the other subgroup included carriers ofgenotype Ala/Ala of the Ala455Val polymorphic marker of the THBD gene and allele Gln of the Arg353Gln polymorphic marker of the F7 gene. The frequency of unfavorable outcomes in the first subgroup was higher than in the second one. The time to an endpoin was 40.5 months (95% confidence interval (CI) 33.5-47.6) in the first subgroup and 51.6 months (95% CI 45.0-58.1) in the second subgroup (chi2 = 4.15, P = 0.042). The results made it possible to assume that the F7 and THBD genes play an important role in genetic predisposition to unfavorable outcomes in patients with a history of acute ischemic heart disease.

[Gene IL6 G(-174)C and gene IL10 G(-1082)A polymorphisms are associated with unfavourable outcomes in patients with acute coronary syndrome].

We investigated the association of gene IL6 G(-174)C polymorphism and gene IL10 G(-1082)A polymorphism with coronary artery disease (CAD) in the Russian population. A total of 1145 patients with CAD diagnose on the basis of clinical studies in cardiological hospitals of Moscow, St -Petersburg, Kazan, Chelyabinsk, Perm, Stavropol and Rostov-on-Don. Supervision term was 9.10 +/- 5.03 months (the maximum term 18 months). In case of gene IL10 G(-1082)A polymorphism we determined that patients with CAD diagnose and A alleles gene IL10 had unfavorable outcome more often than patients with homozygous G alleles. Survival time from end point from carrier genotype GA and AA is 11.68 +/- 0.67 months against 12.69 +/- 0.65 months from carrier phenotype GG gene IL10 (chi2 = 4.13, p = 0.042). The group studied do not differ significantly with respect to the distributions of gene IL6 G(-174)C alleles and genotypes. However in case combined group studies of gene IL10 G(-1082)A polymorphism and IL6 G(-174)C polymorphism we determined that patients with CAD diagnose and carrier genotype GG gene IL6 and genotype GA and AA gene IL10 had unfavorable outcome more often (survival time 11.01 +/- 1.24 months) than patients with genotype CC and CG gene IL6 and genotype GG gene IL10 (survival time 13.28 +/- 0.83 months) chi2 = 10.23, p = 0.017. The obtained data allows assuming the important role of the IL6 and IL10 genes which are responsible for functioning of inflammation system, in the accelerated formation of failures at the patients who had a coronary syndrome.

[Polymorphic markers G(-455)A of gene FGB and C(-1654)T of gene PROC and genetic predisposition to unfavorable outcomes patients undergoing acute coronary syndrome].

We investigated the association of polymorphisms of genes FGB G(-455)A and PROCC(-1654)T with coronary artery disease (CAD) in the Russian population. A total of 1145 patients with CAD diagnose on the basis of clinical studies in cardiological hospitals of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol and Rostov-on-Don. Supervision term was 1.14 +/- +/- 0.33 years (the maximum term 3.2 years). The group studied do not differ significantly with respect to the distributions of G(-455)A alleles and genotypes. However in case of gene PROC C(-1654)T polymorphism we determined that patients with CAD diagnose and Talleles of PROC gene had unfavorable outcome more often than patients with homozygous C alleles. Survival time from end point from carrier phenotype TT and CTis 2.19 +/- 0.18 r. years against 2.46 +/- 0.16 from carrier phenotype CCgene PROC. The obtained data allows to assume the important role of the genes which are responsible for functioning of system of a hemostasis, in the accelerated formation of failures at the patients who had a coronary syndrome.