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The organization of the North-Western District Center for AIDS Prevention and Control (AIDS Center) originates from the onset of the HIV epidemic in the Russian Federation. Over the 35 years of work, the staff of the AIDS Center has made an invaluable contribution to the development of HIV diagnostics, the introduction of new clinical and preventive technologies, patient counseling, and training of qualified personnel. The anniversary article highlights the main stages regarding establishment of the AIDS Center as a structural unit of the Saint Petersburg Pasteur Research Institute. The versatile naturally multidisciplinary functions and tasks related to the AIDS Center organization, its major Russia-wide and global achievements are considered. Special attention is paid to the long-term international cooperation, the results of diverse implemented programs and projects supported by the World Health Organization (WHO) as well as the Joint United Nations Programme on HIV/AIDS. The AIDS Center continues to cooperate with the main scientific facilities such as the Pavlov First Saint Petersburg State Medical University, Institute of Experimental Medicine, N.P. Bekhtereva Institute of the Human Brain of the Russian Academy of Sciences, etc. The ongoing joint research invariably contributes to assessing the epidemiology and clinical course of various viral infections and comorbid conditions. The knowledge acquired becomes regularly summarized and published in a series of monographs, journal articles being presented demonstrated at conferences of various levels. Currently, the AIDS Center is represented by several structural divisions continuing to conduct practical and scientific activities on investigating HIV and viral hepatitis.

The aim of the study was to determine the tropism of the human immunodeficiency virus in patients with virological failure of antiretroviral therapy (ART) from the Arkhangelsk Region based on the analysis of the env gene V3 loop nucleotide sequence.Materials and methods. We used blood plasma samples obtained from 76 HIV-infected persons from the Arkhangelsk Region with virological failure of antiretroviral therapy. The nucleotide sequences of the HIV env gene C2-V3-C3 region were studied by PCR followed by sequencing. The genotype of the studied strains was determined based on the analysis of their phylogenetic relations with reference sequences from the international GenBank database, as well as using specialized programs. To predict viral tropism, the Garrido rule and the online bioinformatic tool Geno2Pheno[coreceptor] were used. The Geno2Pheno[coreceptor] algorithm, determines the false positive rate (FPR) based on the analysis of the env gene V3 loop nucleotide sequence. Results and discussion. Significantly lower representation of R5X4/X4-tropic HIV variants in long-term infected persons with subsubtype A6 virus compared to subtype B virus has been shown. For all FPR cut-off algorithms, a significant correlation between subtype and HIV tropism was observed (p=0.0014 and p=0.013 for FPR 10 % and FPR 20 %, respectively). While among subtype B strains, at least 57 % were identified as R5X4/X4-tropic variants (for an FPR of 10 %), including two strains classified as X4-tropic; among HIV subsubtype A6 even at an FPR of 20 %, the frequency of R5X4/X4-tropic samples only slightly exceeded 22 %. It can be assumed that the dynamics of changes in HIV tropism depends on the virus subtype. Significant differences in the distribution of amino acid residues of the V3 region sequences in the examined group between R5-tropic and R5X4/X4-tropic strains of subsubtype A6 for positions 18 (χ2=7.616, p=0.0058), 21 (χ2=7.281, p=0.007), 24 (χ2=5.587, p=0.0181), and 34 (χ2=5.144, p=0.0233) have been demonstrated. Among the R5X4/X4-tropic strains of the A6 subsubtype, amino acid substitutions were registered at positions 6, 19, 21, 26, 29, 30, which were not found in the R5-tropic A6 strains. The high occurrence frequency of a number of mutations previously described as presumably associated with resistance to maraviroc and similar drugs may indicate a natural polymorphism characteristic of the A6 subsubtype, which does not correlate with resistance to CCR5 co-receptor antagonists.

The main histocompatibility complex — HLA system (Human Leukocyte Antigens) is among the most important genetic factors determining response of humans to infectious agents. The key role that HLA molecules play in immune response is to present the pathogen-derived peptides. Enormous molecular variability of HLA alleles in human populations have attracted close attention and became the basis for numerous studies aimed at evaluating the role of HLA genotypes for individual features of immune response to COVID-19, the new infection caused by SARS-CoV-2 β-coronavirus. Many studies have focused on search of specific alleles associated with both susceptibility and resistance to this disease. Separate HLA patterns were reported already. These patterns may be either universal to several populations, or rather peculiar, since distribution of HLA genes is different for various populations, depending on the living conditions, including specific protection from environmental pathogens. Therefore, it is evident that individual effects of HLA genotype upon occurrence and course of SARS-CoV-2 infection should be performed in comparison with the HLA distribution among the residents of appropriate region. The objective of this study was to compare the distribution of HLA-A*, B*, DRB1* allele groups, and to analyze the frequencies of HLA-AB-DRB1 haplotypes in subjects with COVID-19 (n = 138), compared with the control group presented by residents of the North-Western Russia (n = 1456). The most significant differences between COVID-19 patients compared with a group from control population were revealed for the groups of HLA-A* alleles: the frequencies of HLA-A*02 and HLA-A*26 were significantly reduced (39.86% versus 51.72%, χ2 = 7,58, and 4.35% versus 9.07%, χ2 = 4.17, respectively). At the same time, the frequency of HLA-A*29 was increased more than 2-fold (5.80% versus 2.47%, χ2 = 4.03). This finding suggests that the allele groups A*02 and A*26 are associated with reduced likelihood of the disease, while A*29, is an apparent factor predisposing for susceptibility to the disease. It was found that occurrence of definite HLA haplotypes, including the A*02 allele group, is less common in persons who have undergone COVID-19, and are ranged at the 4th, 7th and 10th positions in frequency, while in the population control group such HLA haplotypes took the 3rd, 4th, 7th and 8th places. Further evaluation of the HLA gene polymorphism will allow to understand the predetermined immunogenetic basis for susceptibility, as well as clinical severity of COVID-19.

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 agerelated 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.

Coronaviruses (CoVs) comprise a polymorphic group of respiratory viruses causing acute inflammatory diseases in domestic and agricultural animals (chicken, pig, buffalo, cat, dog). Until recently, this infection in humans was mainly observed during the autumn-winter period and characterized by a mild, often asymptomatic, course. The situation changed dramatically in 2003, when SARS outbreak caused by pathogenic CoV (SARS-CoV) was recorded in China. A decade later, a new CoV outbreak occurred in the form of the Middle East respiratory syndrome (MERS-CoV), whereas in December 2019, SARS-CoV-2 (COVID-19) cases were recorded, which transformed within the first months of 2020 into the pandemic. In all three cases, CoV disease led to severe bronchopulmonary lesions, varying from dry, debilitating cough to acute respiratory distress syndrome (ARDS). At the same time, multiple changes in innate immunity were noted most often manifested as a pronounced inflammatory reaction in the lower respiratory tract, featured by damaged type II pneumocytes, apoptosis, hyalinization of alveolar membranes, focal or generalized pulmonary edema. Destructive processes in the respiratory tract were accompanied by migration of monocytes/macrophages and granulocyte neutrophils to the inflammatory focus. Such events were accompanied by production of pro-inflammatory cytokines, which magnitude could ascend up to a cytokine storm. SARS-CoV is characterized by symptoms of secondary immunosuppression, manifested by the late onset of interferon production and activation of NLRP3 inflammasomes – the key inflammatory factor. The reason for such reaction may be accounted for by CoV arsenal containing extensive set of structural and non-structural proteins exerting pro-inflammatory and immunosuppressive properties. Delayed IFN production allowed CoV to replicate actively and freely, and when type I IFN synthesis was eventually triggered, its activity was detrimental and accompanied by an aggravated infection course. Thus, SARS can surely be referred to immune-dependent infections with a marked immunopathological component. The purpose of this review was to describe some mechanisms underlying formation of innate immune response to infection caused by pathogenic coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19).

Hepatitis B is an infectious viral disease in which damage or destruction of liver tissue occurs, and which can turn into a chronic form. In chronic hepatitis B (CHB), hepatocytes are replaced by connective tissue as they die, resulting in fibrosis, and then cirrhosis of the liver. Early diagnosis of liver fibrosis is an urgent task in the development of CHB. Already at this stage of the disease, the immune system is activated, which plays a leading role in liver damage in CHB. The main regulators of immune processes are cytokines, which mediate intercellular interactions. A separate group of cytokines are chemokines — proteins of cell migration. In CHB, they are responsible for infiltration of liver tissue by activated white blood cells. Cytokines and chemokines are active participants in fibrogenesis, so they can serve as biomarkers for the development of liver fibrosis, including in the early stages. The purpose of this study was to analyze the content of certain cytokines/chemokines in the peripheral blood of patients with CHB in order to search for potential biomarkers of the initial stages of liver fibrosis. The study included 30 patients with a confirmed diagnosis of CHB with stages of liver fibrosis F0-F1 on the Metavir scale, 36 patients with a diagnosis of chronic hepatitis C (F0-F1) and 37 conditionally healthy individuals as a control group. Concentrations of the following cytokines/chemokines were determined: IFNγ, TNFα, CCL2/MCP-1, CCL8/MCP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC by multiplex analysis using xMAP technology (Luminex, USA). As a result of the study, it was found that in patients with CHB, the plasma content of cytokine TNFα and chemokines CCL2/MCP-1, CXCL9/MIG and CXCL10/IP-10 was increased, and the chemokine CCL8/MCP-2 was reduced, which indicates the possibility of using these cytokines/chemokines as biomarkers of liver damage in CHB. In the examined group of patients with CHB, there was no dependence of the concentrations of cytokines and chemokines in the blood plasma on the viral load, which may be explained by its low level. For plasma cytokines in patients with CHB, correlations were found between TNFα and CCL2/MCP-1 and CCL8/MCP-2 chemokines , which was not observed in the control group. At the same time, in the control group, a correlation was found between the content of TNFα and the chemokine CXCL9/MIG, which was not detected in the group of patients. For both groups, a correlation was found between the content of CXCL9/MIG and CXCL10/IP-10 chemokines. Based on the study data, an algorithm has been developed that allows us to establish chronic hepatitis B or chronic hepatitis C as the cause of the initial form of fibrosis F0-F1 in terms of the content of cytokines IFNγ, CCL2/MCP-1 and CCL8/MCP-2 in blood plasma with a diagnostic efficiency of 89.4%.

In the WHO African region (AFR), measles is characterized by severe complications with a high risk of death due to malnutrition, vitamin А deficiency, concomitant infections. Measles viruses of genotype B (B1, B2, B3) are the endemic viruses in the African region (47 countries). The strategy for the elimination of measles in AFR was based on the combination of supplementary immunization programmes (SIAs) for children under 14 years of age and routine vaccination of at least 90% of children 9-15 months of age. It was recommended to repeat the SIAs every 3-5 years. The number of measles cases decreased by 83-97% during the first year due to the strategy. The recommended age of routine vaccination in AFR is 9 months — this is a way to reduce measles-caused infant mortality. However, the level of seroconversion is not sufficient (85%). To eliminate measles completely by 2020, it’s recommended the use of two-dose regimens — vaccination and revaccination. Vaccination coverage with a single dose of measles vaccine in the African region increased to 74% in 2015, but the high incidence of measles in the region persists. In 2013-2016 there are 103,161 cases of measles among children under 6 years of age in AFR ; 79% of which were not vaccinated (or had unknown vaccination status). In 2013, the measles vaccine program in several AFR countries was disrupted by the epidemic of Ebola. In countries where the epidemic has ended, the vaccination was recommended to be resumed for persons who may have missed routine immunization. There are problems in the implementation of measles elimination in AFR: insufficient equipment of medical centers and lack of qualified personnel, poor population awareness, poorly developed communication system, military conflicts.

Abstract. Present study defines clinical, hormonal and immunological factors allowing to predict outcomes of IVF cycles in patients with combined forms of infertility at their reproductive age. Indices of gonadotrophic ovarian stimulation in IVF cycles in patients of reproductive age with combined forms of infertility depend on their age and cytokine contents in follicular fluid. Effectiveness of gonadotropin-induced ovarian stimulation is inversely dependent on the patients’ age, its increase is related to increased contents of pro-inflammatory cytokines in follicular fluid and increased expression of CCR1, along with decreased expression of CCR3 chemokine receptors in endometrium. Effectiveness of gonadotropin-induced ovarian stimulation depends on concentration of cytokines in the follicular fluid, which is argued by presence of a significant direct correlation between the number of growing follicles, oocytes and local contents of IL-10, IL-15, eotaxin, MIP-1β, RANTES, TNFα, IFNγ, and GMCSF. Free testosterone levels show a positive correlation with numbers of oocytes obtained from the ovarian punctate, and CXCR2 and CCR3 expression in endometrium, as well as a negative correlation was found with IL-4 contents in follicular fluid. In patients with negative IVF cycle outcomes, levels of IL-13 in follicular fluid upon ovarian stimulation proved to be twofold higher than those in patients with successful pregnancy after IVF. Prognosis for pregnancy in a cycle of treatment in patients with combined forms of infertility of reproductive age is determined by a patients’ story, and a variety of clinical, hormonal and embryological factors which can increase predictive accuracy of the IVF outcomes. To determine a probability of successful pregnancy after IVF cycle, an appropriate prognostic index is recommended, with a sensitivity levels of 93% and specificity of 89%.

Background: Over 40 years of use demonstrates that complement 1 esterase inhibitor (C1-INH) concentrate is effective and well tolerated for acute edema attacks and prophylaxis in patients with hereditary angioedema. OCTA-C1-INH is a new stable, virus-inactivated, nanofiltrated concentrate of C1-INH derived from human plasma., Objective: We investigated the pharmacokinetics and safety profile of new C1-INH in people with hereditary angioedema during an attack-free period., Methods: In this prospective, multicenter, open-label, single-arm study, adults with hereditary angioedema type I/II received a single intravenous dose of 20 IU/kg C1-INH. Blood samples were taken ≤30 minutes before infusion, and 0, 0.25, 1, 2, 6, 12, 24, 48, 72, 120, 144, and 168 hours after infusion. The primary end point was assessing the pharmacokinetic parameters of C1-INH measured by C1-INH activity. Safety end points were also examined., Results: Twenty patients received a single dose of 20 IU/kg new C1-INH with a mean (standard deviation) total dose of 1457.3 (356.51) IU. Mean (standard deviation) area under the curve normalized by dose was 51.6 (17.9) h∙IU/mL/IU, maximum blood concentration was 1.14 (0.989) IU/mL, incremental recovery was 0.0466 (0.051) (IU∙kg)/(IU∙mL), half-life was 0.598 (0.716) hours, and time to maximum concentration was 0.598 (0.716) hours. No thromboembolic events were recorded. No treatment-emergent adverse events were rated as severe/serious., Conclusion: PK parameters of new C1-INH were in line with those reported for other C1-INH concentrates. New C1-INH demonstrated a favorable safety profile in patients with C1-INH deficiency. Further studies are warranted to determine the effectiveness and longer-term safety of new C1-INH., (© 2023 The Authors.)