We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial phase I/II of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in volunteers aged 18–60 and open multi-center comparative phase IIb clinical trial in volunteers aged 60 years and older. The safety of the vaccine was assessed in 400 volunteers in the 18–60 age cohort who received two doses of the vaccine (n = 300) or placebo (n = 100) and in 200 volunteers in 60+ age cohort all of whom received three doses of the vaccine. The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AEs), or other significant AEs related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p < 0.05). Immunogenicity assessment in stage 3 of Phase II was performed on 167 volunteers (122 vaccinated and 45 in Placebo Group) separately for the participants who were anti-SARS-CoV-2 nAB negative (69/122 in Vaccine Group and 28/45 in Placebo Group) or positive (53/122 in Vaccine Group and 17/45 in Placebo Group) at screening. On Day 42 after the 1st vaccination, the seroconversion rate in participants who were seronegative at screening was 86.9%, with the average geometric mean neutralizing antibody (nAB) titer of 1:20. A statistically significant (p < 0.05) increase in IFN-γ production by peptide-stimulated T-cells was observed at Days 14 and 21 after the 1st vaccination. In participants who were seropositive at screening but had nAB titers below 1:256, the rate of fourfold increase in nAB levels was 85.2%, while in the participants with nAB titers > 1:256, the rate of fourfold increase in nAB levels was below 45%; the participants who were seropositive at screening of the 2nd vaccination did not lead to a significant increase in nAB titers. In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with over 85% NT seroconversion rates after complete vaccination course in participants who were seronegative at screening in both age groups: 18–60 and 60+. In participants who were seropositive at screening and had nAB titers below 1:256, a single vaccination led to a fourfold increase in nAB levels in 85.2% of cases. These findings indicate that CoviVac can be successfully used both for primary vaccination in a two-dose regimen and for booster vaccination as a single dose in individuals with reduced neutralizing antibody levels.

The Small Intestine Bacterial Overgrowth syndrome ( SIBO) is a widespread pathology both independently and in combination with other diseases of the gastrointestinal tract, therefore, its timely and accurate diagnosis remains a very urgent task.Aim. Purpose of the study: comparative assessment of the diagnostic information content of two methods for diagnosing SIBO—hydrogen-methane breath test (HMBT) and stool analysis for short-chain fatty acids (SCFA).Material and Methods: 65 patients aged from 18 to 76 years were examined. 40 made up the main group, with clinical symptoms of SIBO, and 25—the control group. All patients underwent HMBT with the «SIBRTEST» test kit and stool analysis for SCFA. For both tests, diagnostic sensitivity, specifi city, and accuracy were calculated and comparatively evaluated.Results: HMBT showed sensitivity 90.24%, specifi city 95.83%, accuracy 92.3%. The analysis of feces for SCFA showed, respectively, a sensitivity of 90.24%, a specifi city of 50.0% and an accuracy of 75.38%.Conclusion: HMBT with the SIBRTEST test kit can be recommended in the diagnosis of SIBO. The SCFA test should be treated with caution due to the high probability of false positive results.

INTRODUCTION:Currently, the basis for molecular diagnostics of most infections is the use of reverse transcription polymerase chain reaction (RT-PCR). Technologies based on reverse transcription isothermal loop amplification (RT-LAMP) can be used as an alternative to RT-PCR for diagnostic purposes. In this study, we compared the RTLAMP and RT-PCR methods in order to analyze both the advantages and disadvantages of the two approaches.MATERIAL AND METHODS:For the study, we used reagent kits based on RT-PCR and RT-LAMP. The biological material obtained by taking swabs from the mucous membrane of the oropharynx and nasopharynx in patients with symptoms of a new coronavirus infection was used.RESULTS:We tested 381 RNA samples of the SARS-CoV-2 virus (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) from various patients. The obtained values of the threshold cycle (Ct) for RT-PCR averaged 20.0 ± 3.7 s (1530 ± 300 s), and for RT-LAMP 12.8 ± 3.7 s (550 ± 160 s). Proceeding from the theoretical assumptions, a linear relationship between values obtained in two kits was proposed as a hypothesis; the correlation coefficient was approximately 0.827. At the same time, for samples with a low viral load (VL), the higher Ct values in RT-LAMP did not always correlated with those obtained in RT-PCR.DISCUSSION:We noted a significant gain in time for analysis using RT-LAMP compared to RT-PCR, which can be important in the context of testing a large number of samples. Being easy to use and boasting short turnaround time, RT-LAMP-based test systems can be used for mass screening in order to identify persons with medium and high VLs who pose the greatest threat of the spread of SARS-CoV-2, while RT-PCR-based diagnostic methods are also suitable for estimation of VL and its dynamics in patients with COVID-19.

Significant efforts are being made in many countries around the world to respond to the COVID-19 pandemic by developing diagnostic reagent kits, identifying infected people, determining treatment methods, and finally producing effective vaccines. However, novel coronavirus variants may potentially reduce the effectiveness of all these efforts, demonstrating increased transmissibility and abated response to therapy or vaccines, as well as the possibility of false negative results in diagnostic procedures based on nucleic acid amplification methods. Since the end of 2020, several variants of concern have been discovered around the world. When information about a new, potentially more dangerous strain of pathogen appears, it is crucial to determine the moment of its emergence in a region. Eventually, that permits taking timely measures and minimizing new risks associated with the spreading of the virus. Therefore, numerous nations have made tremendous efforts to identify and trace these virus variants, which necessitates serious technological processes to sequence a large number of viral genomes. Here, we report on our experience as one of the primary laboratories involved in monitoring SARS-CoV-2 variants in Russia. We discuss the various approaches used, describe effective protocols, and outline a potential technique combining several methods to increase the ability to trace genetic variants while minimizing financial and labor costs.

Background. The ongoing pandemic of the novel coronavirus infection (COVID-19) draws attention to the significance of molecular and genetic monitoring of the SARS-CoV-2 spread among the population of the Russian Federation. The aim of the study was to analyze the dynamics of circulation of SARS-CoV-2 genetic variants in Russia.Materials and methods. The analysis of the circulation dynamics for SARS-CoV-2 genetic variants in Russia was carried out, covering the period from 28/12/2020 to 26/6/2022. The analysis included the data from Rospotrebnadzor Report No. 970 "Information about Infectious Diseases in Individuals with Suspected Novel Coronavirus Infection" and the Virus Genome Aggregator of Russia (VGARus). The presence of SARS-CoV-2 RNA was confirmed by the real-time reverse transcription polymerase chain reaction. The primer panels developed at the Central Research Institute of Epidemiology were used for amplification of genomic fragments and the subsequent sequencing.Results and discussion. Using the Russian VGARus platform developed by the Central Research Institute of Epidemiology, we received the data on mutational variability of SARS-CoV-2. By monitoring the circulation of SARS-CoV-2 genetic variants in Russia from 28/12/2020 to 26/6/2022, we found that Delta and Omicron genetic variants prevailed at different stages of the epidemic.Conclusion. The data of molecular and genetic studies are an essential component of epidemiological surveillance, being critically important for making executive decisions aimed at prevention of further spread of SARS-CoV-2 and laying the groundwork for creating new vaccines.

ABSTRACTWe present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in adult volunteers aged 18-60.Safety of the vaccine was assessed in 398 volunteers who received two doses of the vaccine (n=298) or placebo (n=100). The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AE), or other significant AE related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p<0.05).Immunogenicity assessment was performed in 167 volunteers (122 vaccinated and 45 in Placebo Group) separately for the participants who were anti-SARS-CoV-2 nAB negative (69/122 in Vaccine Group and 28/45 in Placebo Group) or positive (53/122 in Vaccine Group and 17/45 in Placebo Group) at screening.At Day 42 after the first immunization the seroconversion rate in participants who were seronegative at screening was 86.9% with average the geometric mean neutralizing antibody (nAB) titer of 1:20. Statistically significant (p<0.05) increase of IFN-γ production by peptide-stimulated T-cells was observed at Days 14 and 21 after the first immunization.In participants who were seropositive at screening but had nAB titers below 1:256 the rate of 4-fold increase in nAB levels was 85.2%, while in the participants with nAB titers >1:256 the rate of 4-fold increase in nAB levels was below 45%. For the participants who were seropositive at screening the second immunization did not lead to a significant increase in nAB titers.In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with 86.9% seroconversion rates in participants, who were seronegative at screening. In participants who were seropositive at screening and had nAB titers below 1:256, a single immunization lead to a 4-fold increase in nAB levels in 85.2% cases.

Background.The COVID-19 epidemic in the Russian Federation, which began in March 2020, caused serious damage to health of the population and led to severe economic losses. By December 28, 2020, 3 078 035 cases of COVID-19 and 55 265 lethal outcomes were registered in the country. The population of all territorial subjects of the country is involved in the epidemic process of COVID-19. The severe epidemiological situation made it necessary to conduct an analysis to identify the factors that determine the high intensity of the epidemic process, as well as the population groups with the highest risk of SARS-CoV-2 infection. Aims to study the patterns of SARS-CoV-2 spread and the epidemiological features of the initial stage of the COVID-19 pandemic in the Russian Federation in 2020. Methods.An epidemiological analysis of the COVID-19 situation in the Russian Federation was carried out to determine the dynamics of morbidity, the gender proportion and age structure of patients, the proportion of hospitalized patients, the ratio of various forms of infection, the social and professional status of patients. Standard methods of descriptive statistics Microsoft Excel and STATISTICA 12.0 (StatSoft, USA) were used for statistical processing. The mean values were estimated with a 95% confidence interval [95% CI] (the exact Klopper Pearson method). Results.During the observation time (2020), several periods were identified in the dynamics of the new COVID-19 cases detection: the period of importation of SARS-CoV-2 and the increase in morbidity, the period of epidemic decline, the period of autumn growth, the period of sustained high incidence of COVID-19. It was found that people over 70 years of age are the group with the highest risk of infection and a more severe course of COVID-19. The presence of target contingents among social and professional groups of the population, which should include medical workers, retired person, employees of educational institutions, law enforcement agencies, transport, who require special attention and medical and social support, was shown. Conclusions.The analysis showed that the large-scale spread of COVID-19 requires in-depth epidemiological studies and the development of additional disease control measures, taking into account the dynamics of the incidence of this socially significant infection.

Aim. Identification of epidemiological patterns of the SARS-CoV-2 spread among the population of St. Petersburg during the one-year COVID-19 pandemic period.Materials and methods. The performed analysis focused on the dynamics of COVID-19 cases in St. Petersburg from 2/3/2020 to 4/4/2021 and on the gender-age profile of patients. The information about patients (age, gender, type of the disease, hospitalization, social, and occupational status) was obtained from the database containing the materials from statistical data form No. 058/u.Results. After one year, the dynamics of reported cases of COVID-19 in St. Petersburg shows two cycles of seasonal surge (spring and autumn-winter) and 8 epidemic periods. It has been found that there are no gender-age differences among COVID-19 patients, which can be seen from the relatively similar number of cases among men and women per 100,000 people in each age group during specific epidemic periods. The strong association between clinical manifestations of COVID-19 and the patients' age was detected: Severe cases were more frequently diagnosed in patients over 70 years, regardless of their gender identity. Based on the social and occupational status, the people who were most exposed to the COVID-19 epidemic process were retirees and people whose occupation was associated with health and safety of St. Petersburg. Among the COVID-19 patients, retirees accounted for 13.69% (men) and 17.67% (women). The proportion of healthcare workers was 3.67% (men) and 9.41% (women).Conclusion. It has been assumed that COVID-19 tends to be a seasonal disease featuring annual autumn-winter epidemic cycles. The study addressed prospects of preventive vaccination against COVID-19 in Russia and the importance of tracking the complications pathogenetically associated with the acute phase of the disease in the system of epidemiological surveillance.

INTRODUCTION:Since the outbreak of the COVID-19 pandemic caused by SARS-CoV-2 novel coronavirus, the international community has been concerned about the emergence of mutations altering some biological properties of the pathogen like increasing its infectivity or virulence. Particularly, since the end of 2020, several variants of concern have been identified around the world, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). However, the existing mechanism of detecting important mutations are not always effective enough, since only a relatively small part of all pathogen samples can be examined by whole genome sequencing due to its high cost.MATERIAL AND METHODS:In this study, we have designed special primer panel and used it for targeted highthroughput sequencing of several significant S-gene (spike) regions of SARS-CoV-2. The Illumina platform averaged approximately 50,000 paired-end reads with a length of ≥150 bp per sample. This method was used to examine 579 random samples obtained from COVID-19 patients in Moscow and the Moscow region from February to June 2021.RESULTS:This study demonstrated the dynamics of distribution of several SARS-CoV-2 strains and its some single mutations. It was found that the Delta strain appeared in the region in May 2021, and became prevalent in June, partially displacing other strains.DISCUSSION:The obtained results provide an opportunity to assign the viral samples to one of the strains, including the previously mentioned in time- and cost-effective manner. The approach can be used for standardization of the procedure of searching for mutations in individual regions of the SARS-CoV-2 genome. It allows to get a more detailed data about the epidemiological situation in a region.

The ongoing COVID-19 pandemic around the world and in Russia remains a major event of 2020. All over the world, research is being conducted to comprehensively study the patterns and manifestations of the epidemic process. The main quantitative characteristics of SARS-CoV-2 transmission dynamics among the population, based on the data of official monitoring over the current situation, play an important role in the development of the epidemiological surveillance system.The aim of this studyis to explore the peculiarities of age-gender distribution of COVID-19 patients in Moscow.Material and methods. The data related to the epidemiological characteristics of age-gender structure of COVID-19 patients in Moscow between March 19, 2020 and April 15, 2020, at different stages of the epidemic were retrospectively analyzed.Results and discussion.The mean age of COVID-19 patients in Moscow was 46,41±20,58 years. The gender ratio (male/female) among the patients was 52.7/47.3 %, wherein the indicators varied depending upon the age. Male/female ratio in the age group “under 39” stood at 53.7/46.3 %, and “over 40 years of age” – at 39.3/60.7 %. The predominant age range among male cases was 19 to 39 years old – 35.4 %, while among female patients – 40–59 years (36.5 %). The age distribution of patients in Moscow is indicative of the fact that COVID-19 is a disease that primarily affects older age groups. The age structure of all COVID-19 cases during the observation period is characterized by predominance of adult patients over 19 years of age – 92,7 % (92,6–92,8 %), the share of patients aged 40–59 years is 35,7% (35,5–35,9 %). The differences in the age distribution in males and females are as follows: in the male cohort, the age groups 19–39 years old and 40–59 years old prevail – 35.4 % (35.1–35.7 %) and 34.9 % (34.6–35.2 %), respectively. The age group 40–59 years old – 36.5 % (36.3–36.8%) dominates in the female cohort.

The Central Research Institute of Epidemiology of Rospotrebnadzor presents priority data obtained from the largescale population PCR-based study of the changes in the rates of circulation of SARS-CoV-2 among relatively healthy residents of Moscow and Moscow Region.

The purpose of the study is to analyze patterns demonstrated by the COVID-19 epidemic process in a megacity during the increase, stabilization and reduction in the incidence, and to evaluate the effectiveness of the epidemic prevention measures.MATERIALS AND METHODS:The comprehensive study incorporating epidemiological, molecular genetic and  statistical research methods was conducted to analyze the spread of SARS-CoV-2 in Moscow during the COVID- 19 pandemic.RESULTS AND DISCUSSION:It was found that the exponential growth in COVID-19 cases was prevented due to the most stringent control and restrictive measures deployed in Moscow to break the chains of SARS-CoV-2 transmission and due to people who were very disciplined in complying with the self-isolation rules. The  analysis of the dynamics in detection of new COVID-19 cases showed that in a megacity, the impact of social distancing and self-isolation would become apparent only after 3.5 incubation periods, where the maximum length of the period is 14 days. It was discovered that the detection frequency of SARS-CoV-2 RNA in relatively healthy population and its dynamics are important monitoring parameters, especially during the increase and stabilization in the COVID-19 incidence, and are instrumental in predicting the development of the epidemic situation within a range of 1-2 incubation periods (14-28 days). In Moscow, the case fatality rate was 1.73% over the observation period (6/3/2020-23/6/2020).CONCLUSION:The epidemiological analysis of the COVID-19 situation in Moscow showed certain patterns of the SARS-CoV-2 spread and helped evaluate the effectiveness of the epidemic prevention measures aimed at  breaking the routes of transmission of the pathogen.

The effect of pulsed ultraviolet (UV) radiation of a continuous spectrum on the inactivation of the novel SARS-CoV-2 coronavirus on metal surfaces was studied. The ability of generators of pulsed UV radiation of a continuous spectrum to completely inactivate the causative agent of COVID-19 within 3 minutes (Alpha-06) and 6 minutes and 45 seconds (Alpha-09) of the installation was confirmed. It has been shown that the use of high-intensity pulsed UV radiation of a continuous spectrum in the general complex of sanitary and hygienic measures for a long time (5 months) allows the personnel of medical organizations, in particular, employees of the laboratory PCR centre, to be protected from the disease of the new coronavirus infection COVID-19.

49 813 sera from persons without clinical symptoms of infectious diseases were tested for IgG to the nucleocapsid protein of SARS-CoV-2 at the Center for Molecular Diagnostics (Central Research Institute of Epidemiology) from May 22 to August 28, 2020. The dynamics of the incidence of seropositive persons was assessed by decades. The maximum seroprevalence was noted at the end of May. Seroprevalence indicators changed slightly from June 21 to August 28 (maximum values, about 17%, were noted from July 1 to July 20), which was consistent with the slowdown in the number of new cases of COVID-19 in the Moscow region