[Herd immunity to SARS-CoV-2 in the Novosibirsk Region population amid the COVID-19 pandemic].

AIM: To determine the level of SARS-CoV-2 seroprevalence among the Novosibirsk Region population against the background of the COVID-19 pandemic. MATERIAL AND METHODS: The work was carried out in 2 phases: 1) a cross-sectional cohort study performed 28.06- 15.07.2020; 2) longitudinal cohort 3-stage seromonitoring: 1st stage 28.06-15.07.2020; 2nd 14.09-04.10.2020; 3rd 10-30.12.2020 The work was carried out according to a unified methodology developed by Rospotrebnadzor with the participation of St-Petersburg Pasteur Institute, taking into account the recommendations of the WHO. IgG antibodies to the SARS-CoV-2 nucleocapsid protein were detected by ELISA using a kit of reagents produced by the SRCMSB (Obolensk) according to the manufacturer's instructions. Statistical analysis was performed using Microsoft Excel 2010 and other programs. RESULTS: The seroprevalence in the region's population was 9.1% (95% CI 8.0-10.2): maximum in children 14-17 years old (17.6%, 95% CI 12.3-23.9) and persons over 75 years (14.8%, 95% CI 11.4-18.8), minimum among persons 30-39 years old (4.9%, 95% CI 3.0-8.0). Increased rate was noted among the unemployed (15.4%, 95% CI 9.9-17.1) and other individuals (13.0%, 95% CI 8.6-18.5). Seroprevalence was 33.3% (95% CI 16.3-59.0) in COVID-19 convalescents and 19.0% (95% CI 13.9-25.0) in contact persons. More than 94.7% (95% CI 91.2-97.2) of seropositive individuals were asymptomatic. During the serological monitoring, seroprevalence increased from 7.4% (95% CI 6.2-8.9) at 1st stage 1 to 12.4% (95% CI 10.6-14.3) at 2nd , and 31% (95% CI 28.8-33.3) at 3rd stage. CONCLUSION: SARS-CoV-2 herd immunity has not reached the threshold level, this does not exclude exacerbation of the epidemic process.

[Features of pathogenesis and COVID-19 course for the elderly and old age.]

The causative agents of coronavirus infection have long been considered the cause of benign respiratory diseases «common colds¼ until their pathogenic types appeared on the epidemic arena: SARS-CoV-1, MERS and finally, SARS-CoV-2. Diseases caused by the listed viruses characterized by moderate invasiveness and noticeable mortality compared to other respiratory viruses. The pathogenesis of these infections is based on a wide range of innate immunity dysfunctions, manifested in the direct suppression of anti-inflammatory functions and, on the contrary, the activation of pro-inflammatory functions, such as the assembly and activation of NLRP3 inflammasome, as well as the synthesis and secretion of pro-inflammatory cytokines and chemokines. Excessive secretion of pro-inflammatory factors is accompanied by a disturbance in the balance of cytokines, leading to the development of a cytokine storm. When the body manages to cope with these disorders, a stable adaptive immunity develops, which is a harmonious combination of cellular and humoral mechanisms of resistance. Particularly difficult COVID-19 occurs in elderly and senile people. It has been shown that the main tests for the risk of multiple organ failure and death in COVID-19 in this category of patients are concomitant diseases, lymphocytopenia, increased transferases, D-dimer and other metabolic disorders. It has been established that critically ill COVID-19 patients develop endothelial dysfunction, thrombotic microangiopathy, immunothrombosis and disseminated intravascular coagulation, which are the basis of multiple organ failure. Pneumonia, as a complication of COVID-19, accompanied by the development of acute respiratory respiratory syndrome, ultimately leads to pulmonary fibrosis, which is often fatal. There is no specific therapy for COVID-19. Recently, immunomodulatory drugs have been widely introduced in the treatment of this infection, including remdesivir, synthetic quinine derivatives and neutralize antibodies.

INFLUENCE OF THE IMIQUIMOD ON THE INTERFERON PRODUCTION AND TREATMENT OF THE EXPERIMENTAL HERPES SIMPLEX VIRUS INFECTION.

BACKGROUND: Imiquimod is an imidazole derivative acting as an immunomodulator on the level of innate and adaptive immune system. Our objective was to evaluate the antiviral activity of generically reproduced imiquimod administered subcutaneously in mice and intravaginally in guinea pigs against herpes simplex virus (HSV), as well as to study the dynamics of serum interferon (IFN) synthesis under different dosing regimens. RESULTS: When administered subcutaneously at doses of 0.5, 1.0 and 10 mg/kg imiquimod increased IFN production in mice in a dose-dependent manner with maximum serum IFN concentrations occurring 4 hours after dosing. Imiquimod protected mice from intraperitoneal HSV infection at doses of 3.2 and 32 LD50.The utmost protection (100% survival) was observed when imiquimod was administered at a dose of 100 mg/kg daily for 5 days before infection. Topical application of imiquimod 5% cream exhibited significantly more rapid and complete virus elimination in guinea pigs intravaginally infected with HSV type 2 compared to control group. CONCLUSION: Imiquimod produced as a generic possesses the same immunomodulatory and antiviral properties as the originally synthesized substance.

[The effect of combination of glycyrrhizic acid with alpha-glutamyl-tryptophan on the experimental adenoviral infection].

In this work, the activity of glycyrrhizic acid (GL) and dipeptide alpha-glutamyl-tryptophane (EW) as single preparations or in combination (GL+EW) against experimental adenoviral infection in the syrian hamsters was studied. Application of gl and GL+EW was shown to decrease the level of the adenovirus replication in liver tissue by 0.6 - 1.2 lgTCID50 depending on the composition and time point of the post infection. It was also demonstrated that normalization of the structure of the liver tissue was required, which was shown on the level of both optical and electron microscopy. The results obtained in this work suggest that gl and GL+EW may be considered as potential component of the complex therapy of adenoviral infection.

Comparative efficiency of pathogen treatment of acute respiratory viral infections.

The article presents the results of clinical studies on the comparative effectiveness of different forms of the drug Cytovir-3 (syrup and powder for solution for oral administration) and Immunal l in the treatment of acute respiratory viral infections in children. It was found in a comparative randomized parallel-group study of 90 children aged two through six years that the drug Cytovir-3 (syrup and powder) became active faster than the comparison drug Immunal, providing normalization of body temperature, reduction of some manifestations of the general intoxication and respiratory syndrome, as well as elevated levels of serum immunoglobulin A. All drugs in the study had an equally normalizing effect on the content of peripheral blood leukocytes and erythrocyte sedimentation rates. The compared products were characterized by good tolerability, lack of side effects and high preventive efficacy against respiratory disease complications. Cytovir-3 drugs (syrup and powder for oral solution) and Immunal had similar ratios of clinical and laboratory safety, efficacy and tolerability. Both products can be used for the treatment of respiratory diseases in children aged two through six years.

[Anti-viral activity of a complex of the glycyrrhizic acid-alpha-glutamyltryptophan against the experimental lethal influenza infection in white mice caused by the oseltamivir-resistant strain of the virus].

Influenza virus is a leading causing factor of infectious respiratory human pathology. The search and development of novel anti-influenza drugs with a wide spectrum of activity is an important goal for medical science. In addition to specific anti-viral activity of the compound, its way of application is of great importance. In this work, we present the results of the study of the activity of a combination of glutamyl-tryptophan with glycirrhyzic acid (GTGA) against oseltamivir-resistant strain of the virus A/Vladivostok/2/09 (H1N1) at per os application on the model of the lethal influenza infection in white mice. The application of the GTGA was shown to decrease the specific mortality of animals (index of protection 43-50%), to increase the mean day of death to 2.5-3.9 days, and to reduce the infectious titer of the virus in the lung tissue to 1.5-1.9 Ig EID50/20 mg. The corresponding values for the reference compound oseltamivir were 14-25%, 1.1-1.9 days and 0.7 Ig EID50/20 mg, respectively, depending on the dose of the virus. The use of the GTGA also led to a reliable increase of the titers of interferon in the blood from 44.3 to 66.3 ME/mL. Morphological analysis revealed that GTGA lead to normalization of the structure of the lung tissue restricting the level of the cytodestruction and inflammation. The results obtained in this work allow the combination studied to be suggested as a promising anti-influenza drug that is active against the drug-resistant virus strains and can be applied orally.

[The anti-viral activity of the complex glycyrrhizic acid-alpha-glutamyl-tryptophan against experimental lethal influenza infection in white mice caused by oseltamivir-resistant strain of the virus].

Influenza virus is a leading causing factor of infectious respiratory human pathology. The ability to implement the antigenic drift and development of drug resistance makes it important to develop novel anti-influenza drugs of wide spectrum of activity. In this work, we present the results of the study of the activity of a combination of glycyrrhizic acid with dipeptide alpha-glutamyl-tryptophan against oseltamivir-reistant strain of the virus Al Vladivostok/2/09 (H1 N1) on the model of lethal influenza infection in white mice. Application of Orvilax was shown to decrease the specific mortality of animals (index of protection 39-67% depending on the dose of the virus and drugs combination), to increase the mean day of death to 3.7-5.0 days and decrease the infectious titer of the virus in lung tissue to 1.3 Ig EID50/20 mg. The corresponding figures for the reference compound Tamiflu were 8-11%, 0.5-1.5 days, and 0.6 Ig EID50/20 mg. The use of Orvilax also led to reliable increase of the titers of interferon in the blood from 30.4 to 56.5 ME/mL. The results obtained allow the drug to be considered as a promising anti-influenza remedy that is active against the drug-resistant virus strains.

[Effect of a combination of glutamyl-tryptophan and glycyrrhizic acid on the course of acute infection caused by influenza (H3H2) virus in mice].

The purpose of the study was to evaluate the modulating effect of glutamyl-tryptophan (EW), glycyrrhizic acid (GA), and their combination on the course of experimental infection caused by influenza A (H3N2) virus in mice. The animals were infected with influenza A/Aichi/2/68 (H3N2) virus in a dose of 1 or 10 LD50. GA (10 mg/kg body weight) and EW (0.1, 10, and 1000 microg/kg) alone or in combination were intraperitoneally injected for 5 days, starting on day 1 of virus infection. Rimantadine 50 mg/kg/day was used as a comparison drug. The combination of EW (1000 microg/kg) and GA (10 mg/kg) was ascertained to exert the maximum protective effect manifesting itself in reducing the death of infected animals (by 75-79% compared to the control depending on the viral dose) and the titers of viruses accumulated in the lung (5-6 log EID50) and in preventing lung tissue edema and inflammation. The noted effect was comparable with that seen in the use of rimantadine. The agents used alone had a lower efficacy than rimantadine. The findings permit the combination of GA and EW to be considered to be a promising agent for the treatment of influenza.

In vitro studies of changes in human endothelial cell functions under the effect of imiquimod.

Imiquimod (1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine) is an active immunomodulator with antiviral effects. In addition to its stimulatory effect on cell-mediated immunity, in vivo studies have detected its antiviral and antiangiogenic effects. Possible direct effect of imiquimod on endothelial cells remains not studied. We have shown that imiquimod inhibited proliferation and migration of human endothelial cells (EA.hy 926 strain) in vitro and induced apoptosis (but not necrosis) of endothelial cells and production of IL-6 cytokine. These results suggest that imiquimod inhibits angiogenesis via direct modulation of endothelial cell function.

[Application thymogen for preoperative preparation of elderly patients with tumor processes in abdominal cavity].

A double-blind, randomized, placebo-controlled study of the efficacy of Thymogen preparation for elderly patients for surgery on the solid tumors in abdominal cavity and retroperitoneal space was carried out. The drug has been administered by intranasal instillation of 100 mg once a day for 7 days before surgery. The isotonic sodium chloride solution for the placebo group in the same scheme was used. The preoperative use of Thymogen proved to be useful to restore the structural and functional parameters of cellular immunity. Immunomodulatory therapy resulted in the significant decrease in the number and range of post-operative complications and the shorting of the postoperative period.

[Clinical significance of the determination of R-proteins in the ejaculate of patients with chronic prostatitis]. / Klinicheskoe znachenie opredeleniia R-belkov v éiakuliate u bol'nykh khronicheskim prostatitom.

Products of cell receptor (R-proteins) catabolic lysis were measured in ejaculate of 121 patients with chronic prostatitis and 15 healthy males. R-protein levels were higher in the patients (U = 172.5; p = 0.047). When immunological indices of the ejaculate (IgA, sIgA, IgG, IgM, interleukin-8) were measured, it was found that in patients with chronic prostatitis there is a positive correlation between concentration of interleukin-8 and content of R-proteins (r = 0.43; p = 0.028). Positive correlation also exists between R-protein content and prostate volume (r = 0.24; p = 0.034) while negative one--between R-proteins concentration and size of the hypoechogenic sites in the prostate (r = -0.25; p = 0.039), between R-proteins in the ejaculate and serum level of fibrinogen B (r = -0.25; p = 0.021). It is inferred that elevation of ejaculate R-protein level occurs in alteration of the prostate. The test for R-proteins in ejaculate can be helpful in detection of early stages of chronic prostatitis.

Crystallisation of crystallizable and amorphous polymer mixtures and peculiarities of their structure: an NMR study.

After isothermal crystallization of the crystallizable poly(ethylene oxide)/amorphous poly(propylene oxide) mixture, partially crystalline structures were formed. They present a specific heterogeneous medium with a hard frame composed of the crystal phase. The isothermal crystallization of the mixture and molecular self-diffusion processes in the amorphous phase of the crystallized mixture was studied by nuclear magnetic resonance relaxation and nuclear magnetic resonance (NMR) with pulsed field gradient. The temporal dependencies of the apparent self-diffusion coefficient were analyzed and the heterogeneity sizes were estimated. The dependence of the heterogeneity size on the crystallization temperature can be qualitatively described by parameter delta, which includes the linear growth rate of the crystal and diffusion coefficient of the amorphous (more mobile) component.

[An error in determining the number of migrants during the trapping of small mammals with weighted lines]. / Oshibka v opredelenii chisla migrantov pri otlove melkikh mlekopitaiushchikh liniiami davilok.

The number of residential animals in daily samples is diminishing regularly during prolonged catching. It might diminish according to exponential law if: (1) the probability to be captured for each animal living on the sampling territory does not alter in the course of trapping; (2) all animals have the same possibility to be captured. The number of captured non-residential (migrating) animals stays the same during he whole period of trapping, thus increasing the number of animal captured at the end of trapping vs. one expected according exponential law. It is not correct however to consider the presence of migrants to be the only reason of the deviation from exponential decrease, because it is observed also in residential animals. (1) Home ranges of some animals overlap the trap line only by their edge. The possibility to capture such animals is 2-3 times lower than animals with central position of home ranges on the trap line. (2) The removal of peculiar demographic groups is not equal. Adult females are captured with highest intensity; young animals, on the opposite, stay uncaptured longer. It may be registered as increasing of proportion of young and subadult animals per an adult female with each day of removal. (3) Reproduction is intensive in summer. Young animals (up to age of 20 days) does not visit traps. Some of them become active in the middle and the end of trapping period when a great share of older animals (including their parents) is already captured. Because of these reasons disturbed exponential removal exists even in residential animals, and we can not differ the real proportion of migrants even in cases when the disturbance of exponential decrease per se is proved properly.

Studies of domain morphology in segmented polyurethanes by pulsed NMR.

A new technique based on the Goldman-Shen pulse sequence with varying preparation interval is proposed for the study of domain morphology of segmented polyurethanes. The results of numerical calculations of the magnetization recovery in different models of domain morphology show that the method provides new information about the domain morphology which is beyond the reach of the conventional Goldman-Shen experiment. A close agreement of the theoretical predictions with the experimental data on samples of segmented polyurethanes with a fixed molecular mass of the hard blocks and variable molecular mass of the soft blocks reinforces the above statement. The resulting structural parameters obtained by this new NMR technique are compared with the data from the small-angle X-ray scattering (SAXS) method.

[Immuno-physiological and hematological aspects of flight certification examination]. / Immunofiziologicheskie i gematologicheskie aspekty vrachebno-letnoi ekspertizy.

Revision of immunophysiological and hematological approaches to medical examination of flight personnel is the focus of this paper. Basing on literary data and results of their own investigations, the authors demonstrate the linkage between occupational impacts on flyers and alterations in the function of specific and non-specific body defense systems. Potential areas for updating flight certification examination procedure, i.e. development of flyers blood and resistance data bank, elaboration of objective immunophysiological and hematological criteria for assessing body response to standard functional tests, comprehensive evaluation of human reaction to exogenic agents and delineation of patterns of correlation between blood and anti-body indices, and other body systems.

[Patterns of the changes in the indices of B-system immunity in acute psychoemotional stress]. / Zakonomernosti izmenenii pokazatelei B-sistemy immuniteta pri ostrom psikhoémotsional'nom napriazhenii.

Psychoemotional stress induces in healthy individuals increased serum Ig and C3 subunit of complement. Response of B immunity psychoemotional stress remains within the limits of basic functioning. State of B immunity in psychologic comfort condition insignificantly depends on individual psychology. Uniqueness on individual immune reactions in psychoemotional stress presents depression of reserved B lymphocytes, which could be easily seen in people of controversial personality type.