VACCINATION against NEW CORONAVIRUS INFECTION in PATIENTS with CARDIOVASCULAR and AUTOIMMUNE DISEASES.

The review article is devoted to a discussion of the issues of vaccination against a new coronavirus infection in patients with cardiovascular and autoimmune diseases. Presented at the time of this writing are data on domestic vaccines safety in the Russian Federation: combined vector vaccines "Gam-COVID-Vac" and "Gam-COVID-Vac-Lyo", peptide-based vaccine "EpiVacCorona", concentrated, purified and inactivated whole-virion "KoviVac" vaccine, and a standalone vaccine/booster shot "Sputnik Light". The analysis of the main contraindication applicable to the vaccines in different categories of patients has been carried out. A number of consensus documents published by Russian and foreign professional medical associations and communities on the issues of vaccination of patients with cardiovascular and autoimmune diseases are considered in detail.Copyright © 2021 Infectious Diseases: News, Opinions, Training. All rights reserved.

[In vitro activity of human recombinant interferon gamma against SARS-CoV-2 virus].

INTRODUCTION: The development of drugs against SARS-CoV-2 continues to be crucial for reducing the spread of infection and associated mortality. The aim of the work is to study the neutralization of the SARS-CoV-2 virus with interferon gamma preparations in vitro. MATERIALS AND METHODS: The activity of recombinant human interferon gamma for intramuscular and subcutaneous administration of 500,000 IU and for intranasal administration of 100,000 IU against the SARS-CoV-2 virus in vitro was studied. The methodological approach of this study is based on the phenomenon of a decrease in the number of plaques formed under the action of a potential antiviral drug. RESULTS: The antiviral activity of recombinant interferon gamma has been experimentally confirmed, both in preventive and therapeutic application schemes. The smallest number of plaques was observed with the preventive scheme of application of the tested object at concentrations of 1000 and 333 IU/ml. The semi-maximal effective concentration (EC50) with the prophylactic regimen was 24 IU/ml. DISCUSSION: The preventive scheme of application of the tested object turned out to be more effective than therapeutic one, which is probably explained by the launch of the expression of various interferon-stimulated genes that affect to a greater extent the steps of virus entry into the cell and its reproduction. CONCLUSION: Further study of the effect of drugs based on recombinant interferon gamma on the reproduction of the SARS-CoV-2 virus for clinical use for prevention and treatment is highly relevant.

Comparative assessment of efficacy and immunogenicity of Gam-COVID-Vac and CoviVac vaccines against SARS-CoV-2

The medical community is interested in the duration of immune protection and the level of specific antibodies (AB) that can pre-vent reinfection with SARS-CoV-2. Objective. To perform a comparative evaluation of efficacy and immunogenicity of Gam-COVID-Vac and CoviVac vaccines against SARS-CoV-2 in a prospective observational study. Material and methods. The following vaccines were used for the vaccination of subjects (n=3322) aged 18 years and older: Gam-COVID-Vac - 1,622 (48.8%) subjects (group I), CoviVac - 1,700 (51.2%) subjects (group II). Vaccinated subjects were fol-lowed up for 6 study visits: before the 1st component of the vaccine, before the 2nd component of the vaccine, 42 days, 3 months, 6 months, and 12 months after the 1st component of the vaccine. Immunoglobulin G (IgG) levels of AB to S protein were compared after the injection of Gam-COVID-Vac and CoviVac vaccines using an enzyme immunoassay. Statistical processing of the obtained data was performed using IBM SPSS Statistics v. 24 and MedCalc v. 20.104 software. Results. Group I subjects showed an increase in specific AB (IgG) levels to SARS-CoV-2 S protein from visit 1 to visits 2 and 3 (p<0.05). In more extended follow-up periods (visits 5, 6), AB levels in groups I and II did not differ significantly and remained sufficiently high by visit 6. Within one year of follow-up, the incidence of COVID-19 (confirmed by polymerase chain reaction) was significantly (p<0.01) lower in the Gam-COVID-Vac group (group I): 22.2% vs. 45.2% in the CoviVac group (group II). The maximum number of days (p<0.05) before the COVID-19 infection was observed in those vaccinated with Gam-COVID-Vac (221 days) compared to those immunized with CoviVac (159 days). Conclusion. The Gam-COVID-Vac vaccine is more effective against COVID-19 and induces a more rapid response of the hu-moral immune system than the CoviVac vaccine. However, the duration of the humoral immune response after administration of Gam-COVID-Vac and CoviVac was similar. Copyright © 2022, Media Sphera Publishing Group. All rights reserved.

Preventive effectiveness of nasal interferon-gamma among adult volunteers against acute respiratory viral infections, including COVID-19

Background. In vitro studies showed effective viral infection block in case of pretreatment with exogenous interferons. Interferon-gamma is a unique immune interferon, actively expressed in patients with acute respiratory viral infections (ARVI) and defending the body from severe infection course. Aim - to evaluate the safety and preventive effectiveness of nasal interferon-gamma protecting against ARVI, including COVID-19. Material and methods. The study enrolled 630 adult volunteers with a negative PCR test result for SARS-CoV-2, without respiratory symptoms and contraindications to interferongamma. Participants were randomized (1 : 1) into 2 groups: the study group - with the use of a prophylactic course of nasal interferon-gamma, and the group of comparison - without a course of prophylaxis. All participants were given a diary for daily monitor respiratory symptoms, adverse events, and record the use of pharmacotherapy. Results. Safety analysis found no differences between groups. During 28 days period a higher incidence of ARVI, including COVID-19, was observed in the group of comparison (13 vs 3 cases in the study group). The odd ratio was 0.224 (95 % CI: 0.040-0.826), p = 0.020. The total number of ARVI cases, including COVID-19, in the group of comparison during 2 months of research was 26 vs 6 in the study group. The odd ratio was 0.233 (95 % CI: 0.077- 0.594), p = 0,001. The longest period of persistence of respiratory symptoms was obtained in the group of comparison (7 vs 4 days in the study group, p = 0.034). Conclusion. Nasal interferon-gamma as a preventive measure contributes to a decrease of infection incidence of ARVI, including COVID-19.

Thrombodynamics parameters in individuals vaccinated against SARS-CoV-2

During the ongoing COVID-19 pandemic, with a significant variety of available vaccines, it is crucial to consider their effects on the hemostasis system. Objective. To study thrombodynamics features of individuals vaccinated against SARS-CoV-2 with Gam-COVID-Vac and Covi-Vac vaccines in a prospective observational study. Materials and methods. Data from 99 vaccinated individuals who completed the first three visits were analyzed. Of these, 18 were vaccinated with Gam-COVID-Vac, and 81 with CoviVac. Venous blood was collected before injection of the components I and II of the vaccine and 42 days after administration of the component I to analyze thrombodynamics parameters using the Thrombo-dynamics Analyzer System T2 (Hemacore, Russia). Results. In the analysis of thrombodynamics test data, no significant differences were found between the Gam-COVID-Vac group and the CoviVac group at any of the three stages of the study. Moreover, no significant increase in any of the parameters from the visit 1 to visit 3 was observed in both groups. Conclusion. The obtained study data suggest that such plasma hemostasis parameters as stationary rate of clot growth and ini-tial rate of clot growth, lag-time, clot density and clot size, spontaneous clots formation time show no significant changes during 42 days after the component I of Gam-COVID-Vac and CoviVac vaccines injection. © 2021, Media Sphera Publishing Group. All rights reserved.

Longterm dynamics of the levels of antiSARSCoV2 Sprotein IgG antibodies in vaccinated individuals

Aim. As part of a prospective observational study, to study the levels of antiSARSCoV2 Sprotein IgG antibodies in individuals vaccinated with the GamCOVIDVac and CoviVac vaccines. Material and methods. The data of 93 people who completed the first 3 visits were analyzed, 23 of whom were vaccinated with the GamCOVIDVac vaccine and 70 people ' with the CoviVac vaccine. We collected blood before the injection of vaccine doses I and II, as well as 42 days after the injection of dose I in order to quantitatively determine Results. A significant increase in antiSARSCoV2 Sprotein IgG antibodies was observed in those vaccinated with GamCOVIDVac. In the group of CoviVac vaccine, an increase in the level antiSARSCoV2 Sprotein IgG antibodies in absolute values was recorded, however, this increase did not reach statistical significance. Conclusion. The data obtained show that the level of antiSARSCoV2 Sprotein antibodies 42 days after GamCOVIDVac vaccination is significantly higher than after CoviVac vaccination. However, an increase in the level of IgG in both groups indicates the ability of both vaccines to stimulate the production of antiSARSCoV antibodies. Keywords: vaccination, coronavirus infection, COVID19, GamCOVIDVac, CoviVac, antiSARSCoV2 IgG antibodies.

VACCINATION against NEW CORONAVIRUS INFECTION in PATIENTS with CARDIOVASCULAR and AUTOIMMUNE DISEASES

The review article is devoted to a discussion of the issues of vaccination against a new coronavirus infection in patients with cardiovascular and autoimmune diseases. Presented at the time of this writing are data on domestic vaccines safety in the Russian Federation: combined vector vaccines “Gam-COVID-Vac” and “Gam-COVID-Vac-Lyo”, peptide-based vaccine “EpiVacCorona”, concentrated, purified and inactivated whole-virion “KoviVac” vaccine, and a standalone vaccine/booster shot “Sputnik Light”. The analysis of the main contraindication applicable to the vaccines in different categories of patients has been carried out. A number of consensus documents published by Russian and foreign professional medical associations and communities on the issues of vaccination of patients with cardiovascular and autoimmune diseases are considered in detail. © 2021 Infectious Diseases: News, Opinions, Training. All rights reserved.

Assessment of Awareness and Experience of Using off-label Drugs by Doctors of Clinical Specialties.

Aim      To evaluate the frequency of off-label prescription of medicines in practice of clinical specialists and the awareness of respondents of the procedure of justified off-label prescription.Material and methods  The sample included 542 clinical specialists who worked in definite medical organizations in 26 entities of the Russian Federation. The respondents were proposed to fill in remotely an anonymous questionnaire to evaluate the experience of prescribing medicines off-label to adult patients.Results Prescribing medicines not in consistence with the officially approved instruction for medical use (off-label or "outside instruction") is a relevant issue of global medical care since convincing scientific evidence for safety of such use is scarce. Analysis of information about off-label prescription is one of current tasks of national medical research centers according to the Federal Project "Development of a network of national medical research centers and implementation of innovative medical technologies". According to the responses about the frequency of off-label prescriptions 67.5 % of respondents reported of no experience of off-label prescription, 27.7 % said "rarely" or "sometimes", and 4.8 % said "frequently" and "very frequently". Specialties of physicians who have more often used medicines off-label (50% and more) included obstetrics and gynecology, pediatrics, rheumatology, hematology, and pulmonology. Cardiologists, neurologists and clinical pharmacologists use medicines off-label relatively rarely (19.6%, 28.6 %, and 22.2 %, respectively). 40 % of medicines used off-label were those designed for the treatment of coronavirus infection SARS-CoV-2. The medicines most frequently used off-label included metformin, rituximab, and thioctic acid. 65 % of respondents assessed their knowledge of off-label prescription as insufficient. In addition, 75 % of respondents consider it useful to receive additional information about risks and benefits of off-label prescription in clinical practice.Conclusion      The survey revealed the need of physicians for information about risks of the off-label use of medicines in clinical practice.

[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.