ASSESSMENT OF INDICATORS OF SPECIFIC HUMORAL IMMUNE AGAINST COVID-19 IN CHILDREN DURING THE DISTRIBUTION OF A NEW CORONAVIRUS INFECTION IN THE IRKUTSK REGION (2020-2021)

Background. There are many aspects ofthe development ofimmunity to the SARSCoV-2virus, that remain poorly understood, like the influence ofage-relatedcharacteristics on the intensity ofimmunity andthe course ofthe disease. Studies ofthe state ofimmunity are widely used, mainly in the adults. But questions ofthe patho- andimmunogenesis in children remain unsolved. Determining the nature ofseroconversion of antibodies to SARS-CoV-2 in this age group is important information for serological monitoring for targeted immunoprophylaxis of the population and forecasting the epidemic situation in the region. The aim. Evaluation of the dynamics of seroprevalence of specific antibodies to SARS-CoV-2 in children of the Irkutsk region during the pandemic of a new coronavirus infection. Materialsandmethods. StudywasconductedamongthechildpopulationoftheIrkutskregion in the periodJune 2020- December 2021as partofthe Rospotrebnadzor projectto assess populationimmunity to SARS-CoV-2in the population oftheRussian Federation. The content ofantibodies to SARS-CoV-2was determinedby ELISAusing native commercial test systems. Results. Population immunity among the child population of the Irkutsk region was characterized by an upward trend from 7.8 % at stage 1 to 98.4 % at stage 6 ofthe study. IgGto SARS-CoV-2remainedin 72.8%andformedin 25.6%ofpreviously seronegativechildren. Antibodiesweredetectedin66.1%ofcasesandpersistedforup to 10-15 months after COVID-19 infection. The proportion of asymptomatic forms of infection among seropositive volunteers was 69.5 %, which determines the high intensity of the latent epidemic process. Conclusion. Thelevelofseroprevalencewas98.4%. Thecurrentresultsofserological monitoring serve as a scientific basis for adjusting the list andscope ofmanagement decisions on the organization of preventive anti-epidemic measures, including vaccination. © 2023 Voprosy Literatury. All rights reserved.

COVID-19: evolution of the pandemic in Russia.Report II: dynamics of the circulation of SARS-CoV-2 genetic variants

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. © 2022, Central Research Institute for Epidemiology. All rights reserved.

COVID-19: the evolution of the pandemic in Russia. Report I: manifestations of the COVID-19 epidemic process

Background. The ongoing pandemic of a new coronavirus infection (COVID-19) determines the relevance of the analysis of epidemiological patterns of SARS-CoV-2 spread among the population of the Russian Federation. Aim — study of the manifestations of the epidemic process of COVID-19 in the Russian Federation in 2020–2022. Materials and methods. A retrospective epidemiological analysis of the incidence of COVID-19 in the Russian Federation was carried out from 03/30/2020 to 04/24/2022. The data from the Rospotrebnadzor report No. 970 “Information on cases of infectious diseases in persons with suspected new coronavirus infection”, information portal Stopcoronavirus.rf, etc. were used. The presence of SARS-CoV-2 RNA was confirmed by real-time RT-PCR. Results and discussion. The analysis of the manifestations of the epidemic process of COVID-19 in the Russian Federation in 2020–2022 showed the presence of two stages which differed depending on the influence of the biological factor and the ongoing anti-epidemic measures. There was a pronounced trend in the development of the epidemic process, starting from megacities (Moscow, Moscow region and St. Petersburg), which are major transport hubs and centers of migration activity of the population, to the regions of the Russian Federation. The SARS-CoV-2 pathogenicity has been shown to decrease with each subsequent cycle of the rise in the incidence of COVID-19 against the background of the increased contagiousness of the virus. Conclusion. As a result of the study, risk areas (megacities) and risk groups were identified. © 2022, Central Research Institute for Epidemiology. All rights reserved.

SEROPREVALENCE OF ANTIBODIES TO SARS-CoV-2 IN CHILDREN AGAINST THE BACKGROUND OF THE COVID-19 EPIDEMIC IN THE RUSSIAN FEDERATION

Objective: To study the seroprevalence of SARS-CoV-2 antibodies (AB) in children in the 2nd year of the COVID-19 pandemic in Russia. Materials and methods: Prospective cohort study. The seroprevalence research was conducted among 3670 children aged 1 to 17 y/o from 26 modelling regions of Russia (that have been participating earlier in the five stages of seromonitoring during 2020-2021). The serological testing was carried out in December, 2021. The work was carried out according to a unified methodology set by the Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being with the Pasteur Institute of Epidemiology and Microbiology (Saint Petersburg, Russia). The plasma was obtained from 3 ml of venous blood, in which the level of AB to nucleocapsid (NC), and the SARS-CoV-2 receptor-binding domain (RBD) was determined by immunoferment method using reagents for qualitative and quantitative analysis. Results: The analysis of AB seroprevalence to NC and RBD showed the statistically significant increase in the share of seropositivity to RBD in children of all modelling regions (p<0.05). The most seropositive volunteers contained low levels of AB: 31.3-125.6 BAU/ml NC and 22.6-220 BAU/ml RBD. An increase in the level of AB to NC and RBD was accompanied by a decrease in the percentage of seropositive patients. Evaluating the contribution of children to the level of humoral immunity, convalescents (had been ill shortly before the examination), the «anamnesis» (had been ill at previous stages of seromonitoring) and asymptomatic (had been asymptomatically ill) groups were distinguished. The maximum contribution was made by children with asymptomatic cases of COVID-19 in anamnesis: In 82.3% (95% CI 81.1-83.6), of which 76.9% (95% CI 75.5-78.3) AB detected to RBD. The contribution of children of two other groups to the overall level of humoral immunity was 33 times less. Conclusion: Statistically significant predominance of AB to RBD above AB to NC and their main contribution to the level of humoral immunity to SARS-CоV-2 (p<0.001).

Peculiarities of Humoral Immunity Formation in Medical Institution Employees Recovered from or Vaccinated against COVID-19 in Irkutsk.

We performed a seroepidemiological survey of the level and structure of population immunity to SARS-CoV-2 among employees of medical institution in the Irkutsk region during the COVID-19 pandemic. Seroprevalence assessment was organized from May 2020 to April 2021. The level of antibodies to SARS-CoV-2 was measured by ELISA. It was found that 139 (46%) of 299 examined workers were seropositive, including 50 (36%) vaccinated against COVID-19, 75 (54%) patients diagnosed with COVID-19, and 14 (10%) asymptomatic cases of SARS-CoV-2. The results obtained should be taken into account when predicting the dynamics of the epidemic process and organizing preventive (antiepidemic) measures, including vaccination.

Algorithm and Results of Short-Term Forecast of Changes in the COVID-19 Spread Coefficient in the Constituent Entities of the Russian Federation

There was a decrease in the number of COVID-19 cases across many entities of the Russian Federation towards the end of summer season-2020. However, the disease remains a relevant threat to the public health and economy and the possibility of a second epidemic wave is not excluded. Rate of infection transmission (Rt) is one of the most important indicators to justify the transition to next stage of removing/introducing restrictive measures on COVID-19. Objective of the work was to describe the algorithm of analysis and short-term forecast of coronavirus spread rate, to assess correspondence between theoretically expected and actual values of this indicator. Materials and methods. Procedure for making a short-term extrapolation forecast of Rt in 10 RF constituent entities, depending on the presence or absence of indicator trends with calculation of a 95 % confidence interval of possible changes in its value is provided. Results and discussion. It is proposed to carry out Rt forecast based on averaged values over a week, combining regression analysis and expert assessment of time series dynamics nature for prompt transition from trend forecasting to extrapolation of stationary observation sequences and vice versa. It has been demonstrated that predicted Rt values are not statistically different from actual values. When making managerial decisions on COVID-19 prevention, special attention should be paid to cases when actual value of Rt exceeds the upper limit of confidence interval. Six (20.0 %) such cases were detected in surveyed entities on calendar weeks 33-35. Three of them were registered in Trans-Baikal Territory, where upward trend was reported during that period of time. The cause of this phenomenon should be analyzed. The put forward algorithm of analysis and forecasting of the Rt value changes, which was tested in 10 entities of Russia, provides a reliable basis for making management decisions on removing/introducing restrictive measures for COVID-19 prevention. © 2021 Russian Research Anti-Plague Institute. All rights reserved.

Population immunity to SARS-COV-2 virus in residents of the irkutsk region in the dynamics of the epidemic

Background. Currently, the COVID-19 pandemic in the world and in Russia remains the main event. In this regard, the study of the manifestations of the epidemic process of the new coronavirus infection COVID-19 and the patterns of its development are an urgent area of research. In the fight against this viral disease, an important role is assigned to the study of the development of population immunity to the SARSCoV-2 virus, which will make it possible to assess the dynamics of seroprevalence and the formation of post-infectious humoral immunity, forecasting the development of the epidemiological situation, elucidating the characteristics of the epidemic process, and will also contribute to planning activities for specific and non-specific prevention of the disease. The aim: to determine the dynamics of population immunity to SARS-CoV-2 among the population of the Irkutsk region during the COVID-19 pandemic. Materials and methods. As a part of the Rospotrebnadzor project of assessing population immunity to SARS-CoV-2 in the population of the Russian Federation, the research has being conducted among the population of the Irkutsk region in the periods from June 23, 2020 to July 19, 2020 (Stage 1), from September 16, 2020 to September 25, 2020 (Stage 2), from December 7, 2020 to December 18, 2020 (Stage 3) and from March 8, 2021 to March 14, 2021(Stage 4), taking into account the reacted one recommended by the WHO. The content of antibodies to SARS-CoV-2 was determined by ELISA using a set of tests for human serum or plasma for specific immunoglobulins of class G to the proteins of the SARS-CoV-2 coronavirus. The results. The research of the humoral immunity of volunteers shows that during the period of an epidemic rise in the incidence of COVID-19 in the Irkutsk region, a low level of seroprevalence was formed (Stage 1 - 5.8 ± 0.5 %, Stage 2 - 12.1 ± 0.7 %), and in conditions of a long-term maximum increase in the incidence rate - 25.9 ± 1.0 % (Stage 3) and 46.2 ± 1.2 % (Stage 4). A significant proportion (Stage 1 - 82.2 ± 3.2 %, Stage 2 - 86.1 ± 2.3 %) of asymptomatic forms of infection characterizes the high intensity of the latently developing epidemic process in the first two stages. High levels of IgG in reconvalescents of COVID-19 persisted for an average of 3 to 5 months. Conclusion. The results of assessing the population immunity to the SARS-CoV-2 virus in the population of the Irkutsk region indicate that the seroprevalence level at Stage 4 of the research was 46.2 %. After the disease, on average, 49.5 % of persons did not detect antibodies. The results obtained should be taken into account when organizing preventive measures, including vaccination, and predicting morbidity. © 2021 Scientific Centre for Family Health and Human Reproduction Problems. All Rights Reserved.

Phylogenetic reconstruction of the initial stages of the spread of the SARS-CoV-2 virus in the Eurasian and American continents by analyzing genomic data.

Samples from complete genomes of SARS-CoV-2 isolated during the first wave (December 2019-July 2020) of the global COVID-19 pandemic from 21 countries (Asia, Europe, Middle East and America) around the world, were analyzed using the phylogenetic method with molecular clock dating. Results showed that the first cases of COVID-19 in the human population appeared in the period between July and November 2019 in China. The spread of the virus into other countries of the world began in the autumn of 2019. In mid-February 2020, the virus appeared in all the countries we analyzed. During this time, the global population of SARS-CoV-2 was characterized by low levels of the genetic polymorphism, making it difficult to accurately assess the pathways of infection. The rate of evolution of the coding region of the SARS-CoV-2 genome equal to 7.3 × 10-4 (5.95 × 10-4-8.68 × 10-4) nucleotide substitutions per site per year is comparable to those of other human RNA viruses (Measles morbillivirus, Rubella virus, Enterovirus C). SARS-CoV-2 was separated from its known close relative, the bat coronavirus RaTG13 of the genus Betacoronavirus, approximately 15-43 years ago (the end of the 20th century).

Dynamics of changes in population immunity to the SARS-CоV-2 virus in residents the Irkutsk region in the context of the COVID-19 pandemic

Background. The ongoing COVID-19 pandemic in the world and in Russia remains the main event in 2020. A comprehensive study of the patterns of development and manifestations of the epidemic process of the new coronavirus infection COVID-19 is an urgent line of research. One of the important aspects of the fight against COVID-19 is the study of population immunity to the SARS-CoV-2 virus in order to assess seroprevalence and the formation process of post-infectious humoral immunity to SARS-CoV-2, forecast the development of the epidemiological situation, identify the features of the epidemic process, as well as planning measures for specific and non-specific disease prevention. The aim of the research is to determine the level and structure of population immunity to SARS-CoV-2 among the humans of the Irkutsk region during the COVID-19 epidemic. Materials and methods. As part of the Rospotrebnadzor project to assess population immunity to SARS-CoV-2 in the population of the Russian Federation, research is being conducted among the population of the Irkutsk region in the periods from 06/23/2020 to 07/19/2020 (stage 1), from 09/16/2020 to 09/25/2020 (Stage 2) and from 12/07/2020 to 12/18/2020 (stage 3), taking into account the reacted one recommended by the WHO. The content of antibodies to SARS-CoV-2 was determined by ELISA using a set of tests for human serum or plasma for specific immunoglobulins of class G to the nucleocapsid of the SARS-CoV-2 virus produced by FBUN GNCPMiB Rospotrebnadzor (Obolensk). The results of a research of the humoral immunity of volunteers show that during the period of an epidemic rise in the incidence of COVID-19 in the Irkutsk region, a low level of seroprevalence was formed (stage 1 – 5.8 ± 0.5%, stage 2 – 12,1 ± 0,7%), and in conditions of a long-term maximum increase in the incidence rate ¬– 25,9±1,0% (stage 3). A significant proportion (stage 1 – 81,2±3,2%, stage 2 – 90.9 ±1,9%) of asymptomatic forms of infection characterize the high intensity of the latently developing epidemic process in the first two stages. High levels of IgG in reconvalescents of COVID-19 persisted for an average of 3 to 4.5 months. Conclusion. The results of assessing the population immunity to the SARS-CoV-2 virus in the population of the Irkutsk region indicate that the seroprevalence level at the 3rd stage of the research was 25.9%. After the disease, on average, 41.6% of persons did not detect antibodies. The results obtained should be taken into account when organizing preventive measures, including vaccination, and predicting morbidity. © 2021, Numikom. All rights reserved.

Trends in epidemic Process Development of tick-Borne encephalitis in the Russian federation, laboratory diagnosis, prophylaxis and forecast for 2021

Tick-borne encephalitis is a natural-focal infection damaging central nervous system, caused by the similarly-named virus transmitted by several species of ixodic ticks. Natural foci of tick-borne encephalitis (TBE) are widely spread in the forest and forest-steppe landscape zones of the temperate climate belt in the vast territory of Eurasia from the Atlantic to the Pacific Ocean. New TBE-endemic territories have been recently identified in Japan, the Netherlands, and in the UK - in 2019. The increasing risk of infection due to the development of tourism and visits to natural foci of TBE became a public health issue of international concern. The aim of the study is to identify modern features of TBE incidence dynamics in the Russian Federation, the state of laboratory diagnostics and prevention and to predict the incidence for 2021. The paper shows that there is a persistent downward trend in TBE-cases in Russia, which is observed through the past few years. The characteristic feature of the epidemic season-2020 was a significant reduction in the incidence of TBE: 989 cases were registered in 33 constituent entities of the Russian Federation (morbidity rate - 0.67 per 100 000 of the population). The sharp decrease of TBE cases in 2020 as compared to 2019 against the background of a decrease in vaccination can be explained, along with natural factors, by the introduction of restrictive measures during the COVID-19 epidemic. The paper also reflects the dynamics of morbidity, seeking the medical services because of tick bites, the infection rate of the carrier, the scope of vaccination, seroprophylaxis, acaricide treatments. The coverage of express-diagnostic tests of ticks for markers of associated pathogens and its availability for the population are presented. It is recognized that the epidemiological situation on TBE in the Russian Federation remains unfavorable. It demands constant attention on the part of healthcare organizations and Federal Service for Surveillance in the Sphere of Consumers Rights Protection and Human Welfare, as well as management decision making aimed at further decrement in TBE incidence through the improvement of prevention measures, specifically in the entities that are characterized by high TBE incidence. The situation requires monitoring of natural foci of infection, enhancement of prophylaxis and treatment of TBE. The paper provides the forecast of TBE incidence for 2021 and values of the 95 % confidence range of the indicator fluctuation, taking into account the presence or absence of trends in its changes in the territory of federal districts and constituent entities of the Russian Federation in 2011-2020. © 2021 Russian Research Anti-Plague Institute. All rights reserved.

FEATURES OF DEVELOPING SARS-CoV-2 NUCLEOCAPSID PROTEIN POPULATION-BASED SEROPREVALENCE DURING THE FIRST WAVE OF THE COVID-19 EPIDEMIC IN THE RUSSIAN FEDERATION

The novel coronavirus (SARS-CoV-2) pandemic, dubbed COVID-19, has become one of the most serious challenges for human populations in the vast majority of countries worldwide. Rapid spreading and increased mortality related to it required new approaches to manage epidemic processes on a global scale. One of such approaches was based on analyzing SARS-CoV-2 seroprevalence associated with COVID-19. Our aim was to summarize the results on assessing seroprevalence to the SARS-CoV-2 nucleocapsid antigen (Nc) in residents from 26 regions of the Russian Federation, carried out during the first wave of the COVID-19 epidemic. Materials and methods. Seroprevalence distribution was examined in 26 model regions of the Russian Federation according to the unified method developed by the Rospotrebnadzor with the participation of the Federal State Institution Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology. Such approach implied formation of a group of volunteer subjects in model geographic region who were tested by ELISA for anti-Nc serum antibody level in peripheral blood. Analyzed primary data obtained in separate regions were either accepted for publication or released. Results. The current paper finalizes the data obtained in all 26 regions of the Russian Federation. The total SARS-CoV-2 seroprevalence was 19.5 (10.0-25.6)% with the maximum and minimum value found in the Kaliningrad Region and the Republic of Crimea, respectively (50.2% vs. 4.3%). A pattern of age-related seroprevalence distribution indicates insignificant predominance of seroprevalence among subjects of 1-17 years old: 22.1 (13.1-31.8)%. Among COVID-19 convalescents positive for SARS-CoV Nc antibodies it reached 60.0 (40.0-73.3)%. The number of contact persons comprised 6285 subjects or 8.5% of total volunteer cohort, with the level of seroprevalence reaching up to 25.3 (17.95-35.8)%. A direct correlation was revealed between levels of seroprevalence in convalescent and contact volunteers. In addition, the reproductive number for SARS-CoV was calculated comprising 5.8 (4.3-8.5) suggesting that one convalescent subject can infect at least 4 healthy individuals. A high level of asymptomatic forms of COVID-19 among seropositive subjects was confirmed empirically comprising up to 93.6 (87.1-94.9)%. Conclusion. A single cross-sectional study performed during 2020 June-August timeframe allowed to assess pattern of sex- and age-related COVID-19 seroprevalence for general population in 26 Russian Federation regions. The data obtained may serve as a basis for the longitudinal cohort investigation with serial subject sampling. The timing and duration of study will be determined by dynamics of ongoing COVID-19 epidemic.

Epidemiological situation on COVID-19 in Irkutsk Region and forecast for its spread

Assessment of a particular territory by its epidemiological significance is very relevant in the light of widespread occurrence of new coronavirus infection, COVID-19, in the Russian Federation. Objective. Detection of the epidemiological features and revealing trends in the epidemic process of new coronavirus infection in the Irkutsk Region and forecasting of its spread. Materials and methods. An operational analysis of the epidemiological situation on COVID-19 in the Irkutsk Region as of August 16, 2020 was performed. Restrictive measures were substantiated based on the calculation of the infection spread rate (Rt). Results and discussion. Irkutsk Region remained one of the adverse territories as regards human COVID-19 incidence in the Siberian Federal District and the Russian Federation as of August 16, 2020. The gradual dynamics of the epidemic process was revealed: at the first stage of the epidemic development it was facilitated by the imported cases from affected countries and regions of the Russian Federation, and subsequently by local transmission. The incidence increase was registered 2 months later than in central regions of the Russian Federation. Currently there is a consistent downward trend. The increase in the cases prevailed among rotation workers staying for shift and seasonal activities in the administrative center and northern districts of the Irkutsk Region. The epidemic pattern was determined by gender, age and social characteristics. It is demonstrated that the risk of the new coronavirus infection is determined by the intensity of contacts in family foci, the spread of infection in medical organizations and a significant proportion of asymptomatic carriers. High lethality rates (0.7 %) and mortality rates (31.1 o/oooo) were established among persons over 65 years. The stationary time series observed since June for changing the Rt-indicator with fluctuations ranging from 0.92 to 1.01 requires maintaining control of restrictive measures with prompt management decisions making based on the evolving epidemiological situation in the Irkutsk Region and taking into account the assessment of its possible complication risks. © 2020 Russian Research Anti-Plague Institute. All rights reserved.

Experience in studying seroprevalence to SARS-CoV-2 virus in the population of the Irkutsk Region during COVID-19 outbreak

Objective of the seroepidemiological study was to determine the level and structure of herd immunity to SARS-CoV-2 among the population of the Irkutsk Region during the period of an increase in the incidence of COVID-19. Materials and methods. The content of antibodies to SARS-CoV-2 was determined by ELISA applying a reagent panel “ELISA anti-SARS-Cov-2 IgG” produced by the State Scientific Center of Applied Microbiology and Biotechnology (Obolensk). Results and discussion. The investigation has revealed that the herd immunity of the total population of Irkutsk Region amounted to 5.8 %. The greatest share of seropositive persons was among the children aged 14–17 (13.8 %) and 1–6 (11.8 %). It has been established that the risk of infection increases by 3.1 times in case of contact with COVID-19 patients. After exposure to COVID-19, antibodies were produced in 56.5 % of the cases. The share of asymptomatic forms among seropositive residents of the Irkutsk Region reached 81.2 %. Consequently, during the chosen period of increased COVID-19 incidence among the population of Irkutsk Region low level of seroprevalence was formed. A significant proportion of asymptomatic forms of infection characterize high intensity of the latently developing epidemic process. The results obtained can be used when organizing preventive measures, including vaccination, and for forecasting morbidity rates. © 2020 Russian Research Anti-Plague Institute. All rights reserved.