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The aim of our work was to assess the occurrence of serological and molecular-biological markers of HIV, HBV and HCV among medical workers from St. Petersburg. Materials and methods. The study material included 171 blood plasma samples from medical workers from St. Petersburg. The ELISA method was used to qualitatively determine HIV antigen/antibodies (Ag/Ab), HBsAg, antibodies to HBs and HBcore proteins (anti-HBs IgG, anti-HBcore total), and anti-HCV IgG. HIV RNA, HCV RNA and HBV DNA were detected by PCR. For all identified HBV samples, sequencing and subsequent analysis of the nucleotide sequences of the Pre-S1/Pre-S2/S region were performed. Results and discussion. The surveyed group was ranked by age into the following subgroups: 21–35 years (28.07 %), 36–50 years (26.90 %), 51–65 years (31 %) and over 66 years (13.45 %). Serological markers of HBV were detected in 91 (53.22 %) subjects, HCV – in 2 (1.17 %). No markers of HIV were detected. At the same time, markers for HBV and HCV were found in 1 (0.58 %) person. HBV DNA was detected in 4 (2.34 %) medical workers; HCV RNA and HIV were not detected. Significant differences in the prevalence and distribution of the analyzed serological markers between age groups were determined. All HBV isolates belong to genotype D, subgenotypes D1 (50 %) and D2 (50 %). High variability of the Pre-S1/Pre-S2/S region of HBV in the examined group has been shown. The results obtained indicate a relatively low prevalence of HBV and HCV in the examined group. Monitoring of the prevalence of blood-borne infections among medical workers remains an urgent task, primarily in relation to HBV.

Chronic hepatitis C (CHC) represents a significant public health concern. In the majority of cases, the infection progresses to a chronic form, which is characterised by the development of fibrosis and cirrhosis of the liver. A plethora of cytokines and chemokines are generated as a consequence of inflammatory processes within the liver. These can exert a dual effect, both protective and damaging, particularly in relation to the death of hepatocytes and the progression of liver fibrosis. Furthermore, a number of growth factors have been identified as playing a role in the pathogenesis of CHC. The objective of the study was a comprehensive evaluation of a wide range of cytokines, chemokines and growth factors in the blood plasma of patients with CHC at varying stages of liver fibrosis. The study cohort comprised 63 patients diagnosed with CHC, who were divided into three groups according to the stage of liver fibrosis. The control group comprised healthy individuals (n = 32). Concentrations of the following cytokines were determined in plasma: Interleukins and some cytokines (IL-1α, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A, IL-17-E/IL-25, IL-17F, IL-18, IL-27, IFNα, IFNγ, TNFα, TNFβ); chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine) and growth factors (EGF, FGF-2, Flt-3L, G-CSF, M-CSF, PDGF-AA, PDGF-AB/BB, TGF-α, VEGF-A) by multiplex analysis based on xMAP technology. Nonparametric statistics methods were used for statistical analysis. As a result of the study, increased concentrations of cytokines IL-12 (p40), IL-15, IL-17E/IL-25, IL-27, IFNγ, TNFα, chemokines CXCL9/MIG and CXCL-10/IP-10 and growth factors FGF-2 and M-CSF were found at all stages of liver fibrosis. Elevated concentrations of cytokines IL-1α, IL-1β, IL-2, IL-6, IL-9, IL-10, IL-17F, IFNα, TNFβ, chemokines CCL2/MCP-1, CCL11/Eotaxin, CCL22/MDC and growth factors G-CSF, TGF-α, Flt-3L were found in severe liver fibrosis/cirrhosis. Correlation analysis revealed a relationship of high significance between the severity of liver fibrosis and the content of cytokines IL-6, IFNγ, TNFα, IL-7, chemokines CCL2/MCP-1, CCL11/Eotaxin, CXCL9/MIG, CXCL10/IP-10, CXCL1/GROα, growth factors TGF-α, PDGF-AA, PDGF-AB/BB. Thus, a certain profile of cytokines characteristic for CHC was revealed, cytokines, chemokines and growth factors significant for liver fibrosis in CHC were found.

A hepatitis B virus (HBV) infection can progress to chronic hepatitis, leading to liver fibrosis, cirrhosis, and hepatocellular carcinoma. CX3CL1/Fractalkine plays a crucial role in recruiting immune cells that are responsible for protecting against HBV infection. The aim of this study was to measure CX3CL1/Fractalkine concentrations in the blood plasma of individuals infected with HBV and to evaluate the role of this chemokine in the development of liver tissue fibrosis. Our study included patients infected with HBV, patients infected with HCV, autoimmune hepatitis, and healthy donors. We analyzed the CX3CL1/Fractalkine concentrations in blood plasma using the xMAP technology. Our results showed that HBV-infected patients had lower concentrations of CX3CL1/Fractalkine. Furthermore, in HBV-infected patients with severe fibrosis/cirrhosis, we observed significantly lower concentrations of CX3CL1/Fractalkine compared to those with no/mild fibrosis. Our study revealed that CX3CL1/Fractalkine concentrations are significantly associated with the stage of fibrosis in HBV infection. We demonstrated that lowered CX3CL1/Fractalkine concentrations might have prognostic value for predicting fibrosis development in liver tissue. Our findings suggest that decreased concentrations of CX3CL1/Fractalkine are associated with an increased risk of progressive liver fibrosis, indicating the potential of this chemokine as a prognostic biomarker for the development of liver fibrosis.

Natural killer cells (NK cells) exert cytotoxicity towards target cells in several ways, including the expression of apoptosis-mediating ligands (TRAIL, FasL). In addition, NK cells themselves may be susceptible to apoptosis due to the expression of TRAIL receptors. These receptors include TRAIL-R1 (DR4), TRAIL-R2 (DR5), capable of inducing apoptosis, and TRAIL-R3 (DcR1), TRAIL-R4 (DcR2), the so-called “decoy receptors”, which lack an intracellular domain initiating activation of caspases. Of particular interest is the interaction of uterine NK cells with cells of fetal origin, trophoblasts, which are potential targets for natural killer cells to carry out cytotoxicity. The aim of this work was to evaluate the expression of proapoptotic receptors and their ligands as well as CD107a expression by NK cells in a model of interaction with trophoblast cells. To evaluate NK cells, we used cells of the NK-92 line; cells of the JEG-3 line were used as target cells. The cytokines IL-1β, IL-15, IL-18, TNFα, IL-10, TGFβ and conditioned media (CM) of the first and third trimester chorionic villi explants were used as inducers. We established that cytokines changed the expression of apoptotic receptors by NK cells: in the presence of TNFα, the amount and intensity of Fas expression increased, while in the presence of TGFβ, the amount and intensity of expression of the DR5 receptor decreased. Soluble chorionic villi factors alter the expression of TRAIL and FasL by NK-92 cells, which can reflect the suppression of the TRAIL-dependent mechanism of apoptosis in the first trimester and stimulating the Fas-dependent mechanism in the third trimester. In the presence of trophoblast cells, the expression of TRAIL and DcR1 by NK cells was reduced compared to intact cells, indicating an inhibitory effect of trophoblast cells on NK cell cytotoxicity. In the presence of chorionic villi CM and trophoblast cells, a reduced number of NK-92 cells expressing DR4 and DR5 was found. Therefore, soluble factors secreted by chorionic villi cells regulate the resistance of NK cells to death by binding TRAIL, likely maintaining their activity at a certain level in case of contact with trophoblast cells.

Introduction. The vertical route of hepatitis B virus (HBV) transmission is a significant problem in African countries, which is characterized by late diagnosis of the disease and high mortality. The high prevalence of hepatocellular carcinoma (HCC) in Africa may be due to variability in the HBV preCore/Core region, mutations in which contribute to disease progression. Molecular genetic characterization of strains circulating among pregnant women may reflect the overall mutational profile of the pathogen in the population. The objective of this study was to analyze the variability of the HBV preCore/Core region circulating among pregnant women in the Republic of Guinea. Materials and methods. The study material included 480 plasma samples obtained from HBV-positive pregnant women from the Republic of Guinea. For all samples, the nucleotide sequences of the preCore/Core region of the HBV genome were sequenced and analyzed. Results. Amino acid variability in the preCore region was determined in 211 (43.96%), and in the Core region in 473 (98.54%) patients. 12 polymorphic sites of the preCore region were identified in which amino acid substitutions occurred, including 8, 2 and 5 positions identified for genotypes E, A and D, respectively. In the Core region, 67 substitution positions were identified, including 46 in samples of genotype E, 23 in HBV genotype A and 26 in genotype D. It was shown that the distribution of substitutions in the preCore and Core regions in HBV genotypes E, A and D differs significantly with a predominance in mutations among HBV genotype E — p 0.0001. Individual characteristic mutations have been identified for each genotype. The most common clinically significant mutations in the preCore/Core region in the study group were identified, including pc-H5D (27,08%), pc-W28* (35,21%), c-E64D (33,54%), c-L116I/V/G (91,46 %), c-T146N (73,13%). The double mutation A1762T/G1764A in the basal core promoter was shown in 74 samples of HBV genotype E, which accounted for 15.42% of the total group and 16.59% of patients with HBV genotype E. Conclusion. The frequency of clinically significant preCore/Core mutations among pregnant women in the Republic of Guinea was determined. The data obtained reflect their prevalence in the general population and can be used to predict the progression of chronic HBV among the region's population.

The aim of this study was to assess the prevalence of occult hepatitis B infection among blood donors in St. Petersburg, as well as to characterize the identified virus isolates. The study material was represented by 2800 blood plasma samples collected in 2019 from blood donors living in St. Petersburg. The ELISA study for HBV marker rate consisted of HBsAg, anti-HBs IgG, anti-HBcore IgG. HBV DNA was analyzed by nested PCR with real-time hybridization-fluorescence detection on three targets allowing to determine virus DNA at low viral load, including HBsAg-negative chronic hepatitis B. Hepatitis B serological markers were detected in 69.43% of those surveyed, HBsAg was found in 0.43% of individuals, and all of which donated blood first time. A significant excess of the anti-HBcore IgG antibodies occurrence among primary donors (15.1%) compared with repeated/regular donors (7.48%) was shown. The prevalence of virus DNA in the group was 3.14%, including 2.71% of cases in HBsAg-negative CHB. Based on phylogenetic analysis of 88 isolates, HBV subgenotypes were determined in the following order: D1 and D2, 40.91% each, D3 and A2, 9.09% each. While determining the serological subtype in detected isolates, the serotype ayw3 (52.27%) vs ayw2 (46.59%) and adw2 (10.23%) prevailed. Drug resistance mutations, including compensatory ones, were detected in six examined patients (6.82%). In all genotype D isolates, multiple amino acid substitutions were identified in the RT, SHB, MHB, LHB, and Core regions; mutations in the preCore region were detected in 21.59% samples. In the MHR of the HBV genotype D genome, twenty-six positions were identified in which amino acid substitutions occurred, and all isolates showed modifications at positions 113, 114, 131, 134, 159, 161, 168, in 76 — at position 122, in 68 — at position 127, in 36 — at position 118, in 24 — at position 128. In HBV A2 isolates, mutations T113S, S143T, Y161F were identified. Nine isolates in the preCore region showed a polymorphism including a stop codon W28*W; in five isolates the W28S substitution was shown in the same position, and the W28*S variant was found in one more sample. The high incidence of HBsAg-negative CHB cases among blood donors, as well as the predominance of HBV isolates that simultaneously carry mutations resulting in diagnostic failure of HBsAg tests and prophylactic failure of immunoglobulin or vaccines and virus reactivation, mutations that contribute to disease progression obviously pose a threat to health and require to be further examined.

Human immunodeficiency virus (HIV) continues to be a global health challenge, with over 38 million people infected by the end of 2022. HIV-1, the predominant strain, primarily targets and depletes CD4+ T cells, leading to immunodeficiency and subsequent vulnerability to opportunistic infections. Despite the progress made in antiretroviral therapy (ART), drug resistance and treatment-related toxicity necessitate novel therapeutic strategies. This review delves into the intricate interplay between HIV-1 and host cellular proteins throughout the viral life cycle, highlighting key host factors that facilitate viral entry, replication, integration, and immune evasion. A focus is placed on actual findings regarding the preintegration complex, nuclear import, and the role of cellular cofactors such as FEZ1, BICD2, and NPC components in viral transport and genome integration. Additionally, the mechanisms of immune evasion via HIV-1 proteins Nef and Vpu, and their interaction with host MHC molecules and interferon signaling pathways, are explored. By examining these host–virus interactions, this review underscores the importance of host-targeted therapies in complementing ART, with a particular emphasis on the potential of genetic research and host protein stability in developing innovative treatments for HIV/AIDS.

According to recent data, there are currently 170 to 200 million people infected with HCV worldwide, and the number of new cases annually is approximately 40,000. Thus, the overall prevalence of the pathogen in the world is about 1.8–3%. The dynamic monitoring of circulating viral variants in specific groups that reflect the situation in the wider population, including potential pathogen spread, is of high importance for predicting the epidemiologic situation. Pregnant women are such a group. The Republic of Guinea is one of the poorest countries in the world, in which medicine receives little finance from the state. Among other conditions, HCV infection is not monitored in the country. This work used blood plasma from pregnant women living in the Republic of Guinea and their partners (1810 and 481). ELISA diagnostic kits were used to detect serologic markers, and PCR diagnostic kits were used to detect molecular biologic markers. Sanger sequencing, followed by phylogenetic analysis, was used for genotyping. The present study shows that HCV antibodies were detected in 3.2% of the pregnant women examined and in 3.33% of their male partners. HCV RNA was detected in 0.5% of cases in women and in all anti-HCV-positive male partners (3.33%). HCV RNA was more common in the men than in the pregnant women (χ2 = 25.6, df 1, p < 0.0001, RR = 6.69 with 95% CI: 2.97–15.04). The HCV viral load was determined for all the RNA-HCV-positive samples. The HCV viral load exceeded 1000 IU/mL in all nine women and only in two cases in men. The HCV genes NS5A and NS5B and the NS3 gene fragment were sequenced for 11 samples. Subtype 2q was determined for three isolates and 2j for another three isolates. Another five isolates could not be confidently assigned a subtype because different results were obtained with different methods of analyzing the three viral regions. It can be assumed that these isolates belong to new viral subtypes or to recombinant forms between genotype 2 subtypes. No drug resistance mutations were identified, but a large number of natural polymorphisms in the analyzed genomic regions of the HCV isolates were shown. These results may serve as baseline data for the future planning of a nationwide estimate of the prevalence of bloodborne infections among pregnant women.

According to the WHO data, the number of infected people exceeded 765.2 million people during the COVID-19 pandemic. The severity of patient’s condition is determined by immune system hyperactivation. Activation of T- and B-lymphocyte subsets plays a prominent role in the control of infectious process. A content of small circular DNA molecules — T-cell receptor excision circles (TREC — T-cell receptor excision circles) and B-cell (“kappa”) excision rings (KREC — Kappa-deleting recombination excision circles) — in the peripheral blood can be used as a marker of the functionally active T and B cells maturation. The purpose of this work is to quantify peripheral blood TREC and KREC level in patients with the new coronavirus infection COVID-19 of varying severity.Materials and methods.The material consisted of 1028 blood samples from patients with a confirmed diagnosis of COVID-19, as well as 717 blood samples from apparently healthy volunteers. The content of TREC and KREC DNA fragments in the total DNA fraction was assessed by quantitative Real-time PCR using the “TREC/KREC-AMP PS” test system (St. Petersburg Pasteur Institute, Russia). Blood cell phenotyping was carried out using flow cytometry.Results.TREC/KREC levels were significantly reduced in COVID-19 patients (p 0.0001 at 95% CI). A significant direct correlation was established between the levels of peripheral blood TREC molecules and level of CD45+CD3+CD19–T cells (r = 0.59, p 0.0001), as well as between KREC level and count of CD45+CD3–CD19+B cells (r = 0.66, p 0.0001). The level of TREC molecules in patients with severe vs. moderate infection was significantly reduced in patients aged 30–39 years old (p = 0.0404) and 40–49 years old (p = 0.0356). The negative correlation between severity of COVID-19 clinical manifestations and TREC level in the blood of patients in 30–49 year age group indicates about an opportunity of using this analyte as a diagnostic and prognostic laboratory marker of patient’s condition. A simple PCR analysis algorithm makes it relevant to use the described method for assessing a state of immunity in coronavirus patients in the context of systemic negative impact of the SARS-CoV-2 virus on human organism.

T-cell immune response is extremely important in protecting human body from diverse viral infections. It is known that it can ensure viral clearance and complete recovery in patients with humoral immunodeficiency. COVID-19 patients were found to have T-cell response primarily directed against SARS-CoV-2 structural S, M, N, E proteins, with nucleocapsid protein being most conserved. To assess patients immunity against coronavirus infection and evaluate an effectiveness of vaccine candidates, it is necessary to develop an optimal diagnostic antigen to evaluate arising T-cell response against SARS-CoV-2 antigenic determinants. A diagnostic test to determine host specific susceptibility to SARS-CoV-2 infection should target conserved regions of global SARS-CoV-2 variants. The study was aimed to develop a structure of an antigen bearing conserved and immunogenic sequences derived from SARS-CoV-2 structural proteins and to obtain an Escherichia coli producer strain containing a recombinant protein to be subsequently used for assessing antiviral T-cell immunity. Developing of the antigen was performed in silico: TepiTool and NetMHCIIpan were used to predict and identify high affinity epitopes spanning SARS-CoV-2 E, M, N, S proteins and MHC II binding. Several variants of recombinant antigen proteins were constructed, from which one was selected based on its physicochemical properties: isoelectric point, hydrophobicity index and aliphatic index, as well as 3D representation built by using the I-TASSER. The sequence was synthesized and cloned into the pET24a(+) vector. The resulting plasmid pCorD_PS was transformed into E. coli DH5 followed by Rosetta (DE3). The strain-producer of the recombinant E. coli protein CorD_PS was assessed for the presence and stability of IPTG-induced antigen protein expression and elimination of recombinant coronavirus antigen-bearing plasmid. Based on the study data, an antigen was developed consisting of conserved regions from SARS-CoV-2 S, M, N, E proteins. A 53 kDa recombinant protein was predicted to be stable in aqueous solutions with isoelectric point of 9.56 potentially allowing to simplify protein purification from E. coli cells. Plasmid DNA pCorD_PS (6695 bp) encoding final recombinant coronavirus antigen cloned into pET24a(+) vector was obtained. A stable, productive E. coli CorD_PS strain was obtained. The obtained strain-producer resulting in recombinant E. coli CorD_PS antigen is stable allowing to move on to design antigen purification technique and further develop SARS-CoV-2-specific diagnostic test system.

Background. The course of the COVID-19 epidemic process depends on population immunity which prevents pathogen spread. Aim: to study an evolution of SARS-CoV-2 humoral immunity in the Belarusian population rela- tive to COVID-19 pandemic dynamics. Materials and methods. The work was carried out according to a methodology for assessing herd immunity developed by Rospotrebnadzor (Russia) and the Belarusian Ministry of Health involving the St. Petersburg Pasteur Institute (SPPI) by taking into account the WHO recommendations. The study was approved by the Bioethics Committee of Belarus and the SPPI Bioethics Committee. Participant selection was carried out by ques- tionnaire using a cloud (internet server) service. To monitor herd immunity, a cohort of 4661 subjects (involved at all stages of seromonitoring) was formed from the total volunteer group. Study subjects were randomized into groups based on age (117, 1829, 3039, 4049, 5059, 6069, 70+ years), geographic region, and occupation. For the detection of antibodies (Abs) against SARS-CoV-2 nucleocapsid (Nc) and S glycoprotein receptor-binding domain (RBD), rel- evant assay systems were used according to the manufacturers instructions. A four-stage study was conducted according to a unified scheme. Results. At stage 1 (pandemic month 15), herd immunity was mainly accounted for by Nc+RBD+ Ab status alone. By stage 2 (4 months later), its specific proportion decreased by 1.2-fold, whereas percentage of subjects solely bearing RBD-specific Abs increased by 1.7-fold. At stages 3 and 4 (9 and 19 months after the onset) vs. stage 2, percent- age of subjects with RBD+Nc decreased by 3.5%; the proportion of persons with Nc+RBD Abs increased by 1.5-fold. The most important contributor in herd immunity turned out to be due to population vaccination, with coverage reaching 70% by stage 4. Among vaccines, compared with whole-virion, inactivated BIBP-CorV vaccine the Sputnik V and Sputnik Light vector were used most often. Conclusion. The evolution of herd SARS-CoV-2 humoral immunity included a series of changes in circulating Ab levels (Nc, RBD). The hybrid immunity formed helped to reduce the incidence of COVID-19 to sporadic level.

The aim of the work was to estimate the prevalence of HIV, HBV and HCV markers among pregnant women and their male partners in the Republic of Guinea.Materials and methods. The material of the study was blood plasma samples from 140 pregnant women living in Kindia prefecture and N’Zerekore prefecture, as well as 60 male partners who reported sexual contact with HIV-infected persons. The samples were examined for the presence of serological (HBsAg, HBeAg, antibodies anti-HBs IgG, anti-HBcore IgG, anti-HBe IgG, anti-HCV IgG, Ag/Ab-HIV) and molecular (HBV DNA, HCV RNA, HIV RNA) markers.Results and discussion. The age of the examined pregnant women ranged from 13 to 55 years and was on average (26.29±9.67) years. The age of men varied from 15 to 60 years, on average – (29.05±11.99) years. When assessing the prevalence of serological markers, antibodies to HCV were detected in 2.14 % cases in women and in 3.33 % cases in men. Antibodies to HIV were found in 6.43 % and 6.67 % women and men, respectively. Serological markers associated with HBV were detected in 80.71 % (HBsAg – 13.57 %) of women and 81.67 % (15 %) of men. In the pregnant women, HCV RNA was not detected, HIV RNA was revealed in 1 case, HBV DNA was identified in 26 cases (18.57 %), including 5 % HBsAg-negative hepatitis B cases. In the men group, HCV RNA and HIV RNA were detected in 3.33 % and 6.67 % cases, respectively. HBV DNA was determined in 16.67 % of men, including latent hepatitis B in one person. A significantly higher incidence of HIV in men compared to women is shown (χ2=3.907 at p

The aim of the work is to assess the prevalence of hepatitis B virus drug resistance mutations and immune escape mutations in pregnant women in the Republic of Guinea. Materials and methods. Blood plasma samples obtained from 480 pregnant women from different regions of the Republic of Guinea with laboratory-confirmed viral hepatitis B were studied. Nucleotide sequences for genotype identification and mutation detection were obtained using nested-PCR followed by Sanger sequencing, based on overlapping pairs of primers spanning the complete genome of the virus. Results and discussion. In the examined group, the viral genotype E was the most prevalent (92.92%) compared with subgenotypes A1 (1.67%), A3 (1.46%), D1 (0.63%), D2 (1.04%) and D3 (2.29%). Among the examined HBV-infected pregnant women, 188 (39.17%) had undetectable HBsAg. Drug resistance mutations were detected in 33 individuals, which amounted to 6.88%. The following mutations were found: S78T (27.27%), L80I (24.24%), S202I (15.15%), M204I/V (42.42%). The presence of polymorphic variants not described as drug resistant has also been shown in positions associated with the development of drug resistance to tenofovir, lamivudine, telbivudine and entecavir (L80F, S202I, M204R). When analyzing the MHR and the region of a determinant, mutations were detected in 318 (66.25%) of pregnant women. In 172 of them, which amounted to 54.09%, multiple mutations were found. The amino acid substitutions in 13 positions associated with HBsAg-negative hepatitis B and/or potentially affecting HBsAg antigenicity were identified. Conclusion. The high prevalence of immune escape and drug resistance mutations potentially associated with false-negative result of HBsAg screening, prophylaxis failure, and virological failure of therapy that has been identified among treatment naive pregnant women imposes a serious problem.

Traumatic brain injury (TBI) results in a significant inflammatory burden that increase the production of inflammatory mediators and biomarkers. The immune system plays a key role in the pathogenesis of traumatic brain injury. Neuroinflammatory mediators released from resident glia (activated microglia and astrocytes) inside the brain recruit immune cells where cytokines are small soluble proteins that confer instructions and mediate communication among immune and non-immune cells. Interleukin-6 (IL-6) is a proinflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. The purpose of the current study was to assessment of cerebrospinal fluid (CSF) interleukin-6 (IL-6) and MBP levels in patients with TBI. Samples of cerebrospinal fluid of 85 patients with TBI were examined. Concentrations IL-6 were measured via xMAP multiplexing technology. The control was the course of CSF in patients with concussion. An increased content was found in all patients with traumatic brain injury: 19.59 pg/mL in the group with mild traumatic brain injury; 103.6 pg/mL in the group with moderate traumatic brain injury; and 2225 pg/mL in the group with severe traumatic brain injury load versus 2.58 pg/mL in the control group. A direct correlation was found with the presence of basic myelin proteins in the cerebrospinal fluid, which indicates the degree of damage and neurodegeneration processes. Identification of the features of IL-6 content in patients with brain injury may indicate its important role in the course of disease. It also requires additional more detailed study, including comparison with IL-6 content in peripheral blood.

In this article, we explore the role of macrophage-derived chemokine (MDC/CCL22) in COVID-19 immunity. The study included plasma samples of 289 patients with PCR-verified COVID-19 from specialized hospitals. The blood samples were collected at admission, approximately 7 days after the start of infection. Genetic testing of the virus was performed in nasopharyngeal swabs to determine the viral strain for each patient. We also included blood plasma of 69 convalescent patients who had recovered from COVID-19 more than a month prior to the study. Additionally, 51 healthy donors were included in the study as controls. The concentrations of MDC/CCL22 and other cytokines and chemokines were measured with multiplex analysis using Luminex MagPix Technology. The results showed that COVID-19 patients had significantly lower MDC levels in their plasma, regardless of the SARS-CoV-2 strain, compared to healthy donors. This finding suggests that MDC/CCL22 depletion may play a role in COVID-19 immunity. Furthermore, convalescent patients still showed decreased concentrations of MDC/CCL22 more than a month after infection, indicating that this depletion may persist even after recovery. We propose two mechanisms that can explain the reasons leading to MDC/CCL22 depletion. The first is binding and inactivation of this chemokine with SARS-CoV-2 peptides, making it not only undetectable for commercial kits, but also less functionally active. Another mechanism is the dysfunction of its effector cells (e.g., DCs and macrophages). Lymphopenia following COVID-19 can potentially be explained by the absence of MDC/CCL22. This may lead to a shift towards hyperactivation in the inflammatory response, potentially explaining the severity of COVID-19. This research sheds light on the importance of MDC/CCL22 in COVID-19 immunity and highlights the need for further investigation into its role in the disease. Understanding the mechanisms behind MDC/CCL22 depletion could provide new insights into the pathogenesis of COVID-19 and inform the development of potential treatments.

The ongoing coronavirus disease (COVID-19) pandemic over the past three years has caused close attention to the problem of herd immunity, which is understood as: "resistance to the spread of a contagious disease within a population or herd". Collective immunity is formed both as a result of infection (natural spread of the pathogen in a population of susceptible individuals) and as a result of the use of specific vaccines. During the COVID-19 pandemic, both mechanisms for the formation of collective immunity were realized. In the first wave, there was a natural formation of collective immunity to the virus following recoveries from COVID-19 caused by pandemic spread of SARS-CoV-2. Starting from December 2020, the widespread use of specific vaccines against SARS-CoV-2 began in the USA, Great Britain, China, Russia, and a number of other countries. This launched the process of post-vaccination collective immunity formation; its features have depended on the vaccine types implemented. Currently, in those countries where vaccination and revaccination of recovered patients is widely carried out, immunity is "hybrid" in nature. Several commonalities should be noted in the pandemic experience: a somewhat regular, periodic (wavelike) nature of the COVID-19 epidemic process; changes in pathogen genetics in variants in all countries; and expansive mass vaccination programs in many populations. From these, we can draw some conclusions about the general trend for all countries in the formation of collective immunity during the pandemic: At the beginning of the pandemic in 2020, overall population seroprevalence did not exceed 20%. Other findings were: the highest seroprevalence rates were noted in the children's age group; pronounced regional differences were revealed; and the highest indicators were noted among medical workers. Collective immunity developed as a result of infection or illness, and in the majority of seropositive volunteers, it was represented by antibodies to both antigens. At the height of the pandemic in the summer of 2021, population seroprevalence reached 50%. This was due to both a significant number of convalescents and the start of mass vaccination campaigns. In all countries, specific differences in seroprevalence (by age, region, profession) leveled out, leading to more uniformity. During this period, the formation of "hybrid" immunity is clearly prominent, and the proportion of individuals with antibodies to RBD alone increased (due to vaccination with vector vaccines). Later, mass vaccination, as well as involvement of most of the population in the epidemic process due to the emergence of the highly contagious Omicron strain, raised the level of collective immunity to 80-90%. This led to a sharp decrease in COVID-19 incidence in the second half of 2022 in all countries participating in the study. In the later stages of the pandemic (2022-2023), almost 90% of seropositive volunteers had hybrid immunity, reflected as antibodies to both antigens (Nc, RBD).

C1 inhibitor of serine proteases (C1-INH) performs a regulatory function in the complement system and vascular permeability. Deficiency of C1-INH leads to various forms of angioedema, including hereditary angioedema (HAE). The cause of HAE is a genetically determined violation of the synthesis of C1-INH. A decrease in the level of C1-INH to 50% relative to the norm leads to an increase in the production of bradykinin, which is the basis for the diagnosis of HAE. The development of affordable ELISA for the quantitative determination of C1-INH is a popular direction for clinicians. During the development of a new kit for quantitative determination of C1-INH, two mouse monoclonal antibodies (mAb) with different epitope specificities were obtained. On their basis, a sandwich-type ELISA was developed. The specificity of the obtained mAb's was confirmed using the medical device “Berinert”. To prepare calibrators, C1-INH was affinity purified from human blood plasma using a sorbent with immobilized mAbs. The identity of the C1-INH protein was confirmed by PAGE electrophoresis, immunoblotting, and mass spectrometry on MALDI-TOF/TOF UltrafleXtreme mass spectrometer. To assess the quality indicators of developed reagents kit, studies were carried out in accordance with GOST R 51352-2013 and TU 21.20.23-041-01967164-2022. Values of quality indicators: accuracy — 93.53%; measurement linearity interval — 22.00-176.07 ng/mL. Using the developed ELISA test system, we examined 28 blood sera from healthy donors and 7 blood sera from patients with confirmed HAE. In the same samples, the content of C1-INH was determined by turbidimetric method, using the "Diagnostic reagents for in vitro immunochemical studies of specific blood proteins. Model: C1-esterase inhibitor (C1 EsteraseInhibitor)" (Aptec, Belgium). The correlation coefficient was 0.94 (p < 0.05). It was found that the diagnostic sensitivity and specificity of the developed ELISA is 100%. As a result of the study, an original ELISA test system for the quantitative determination of C1-INH was developed "Reagent kit for enzyme-linked immunosorbent assay of human C1-inhibitor (C1-inh PS)".

The chemokine receptor CXCR3 and its ligands (MIG/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11) play a central role in the generation of cellular inflammation, both in the protective responses to invading pathogens, and in different pathological conditions associated with autoimmunity. It is worth noting that CXCR3 is highly expressed on innate and adaptive lymphocytes, as well as on various cell subsets that are localized in non-immune organs and tissues. Our review focuses exclusively on CXCR3-expressing T cells, including Th1, Th17.1, Tfh17, Tfh17.1, CXCR3+ Treg cells, and Tc1 CD8+ T cells. Currently, numerous studies have highlighted the role of CXCR3-dependent interactions in the coordination of inflammation in the peripheral tissues, both to increase recruitment of CD4+ and CD8+ T cells that upregulate inflammation, and also for recruitment of CXCR3+ T regulatory cells to dampen overexuberant responses. Understanding the role of CXCR3 and its ligands might help to apply them as new and effective therapeutic targets in a wide range of diseases.

Recent studies have demonstrated the relationship between vitamin D deficiency, infection severity and mortality from COVID-19. This study aimed to analyze the vitamin D metabolites and cytokine expression levels of COVID-19 patients who were hospitalized with bolus cholecalciferol supplementation. Materials and methods: This study represents the next stage of the open-label randomized pilot conducted by the Almazov National Medical Research Centre. A total of 44 hospitalized patients, comparable in demographic, clinical, laboratory and instrumental baseline characteristics, with moderate/severe COVID-19 were included. All patients had similar doses of concomitant corticosteroid therapy. Twenty-two patients received 50,000 IU cholecalciferol on the first and eighth days of hospitalization. The serum 25(OH)D, 1,25(OH)2D and 28 plasma cytokines were estimated for each group initially and on the ninth day of hospitalization. Results: Initially, there were no differences in the 1,25(OH)2D and cytokine levels in patients with vitamin D deficiency and normal 25(OH)D. Bolus cholecalciferol therapy at a total dose of 100,000 IU led to an increase in 25(OH)D levels in hospitalized patients with COVID-19, while the levels of the active metabolite (1,25(OH)2D) did not show significant differences between the groups or in its increased level over time, regardless of cholecalciferol supplementation. Furthermore, cholecalciferol supplementation at a total dose of 100,000 IU did not affect the majority of the cytokines estimated on the ninth day of hospitalization, except for the pro-inflammatory marker IL-1b, the concentration of which was lower in the group of patients without vitamin D supplementation. Conclusions: The 25(OH)D level was positively associated with an anti-inflammatory immune response, but cholecalciferol supplementation at a total dose of 100,000 IU did not affect the active-form vitamin D or cytokine expression levels. This fact may be explained by the impact of corticosteroid therapy, and it requires further investigation in a post-COVID-19 context.

The widespread use of the oral poliovaccine from Sabin strains (tOPV) radically reduced poliomyelitis incidence worldwide. However, OPV became a source of neurovirulent vaccine-derived polioviruses (VDPVs). Currently, circulating type 2 VDPVs (cVDPV2) are the leading cause of poliomyelitis. The novel OPV type 2 vaccine (nOPV2), based on genetically modified Sabin strain with increased genetic stability and reduced risk of cVDPV formation, has been used to combat cVDPV2 outbreaks, including one in Tajikistan in 2021. In order to identify the importation of cVDPV2 and nOPV2-derivates, stool samples from 12,127 healthy migrant children under 5 years of age arriving from Tajikistan were examined in Russia (March 2021–April 2022). Viruses were isolated in cell culture and identified via intratype differentiation RT-PCR, VP1 and whole-genome sequencing. cVDPV2 isolates closely related with the Tajikistan one were isolated from two children, and nOPV2-derived viruses were detected in specimens from 106 children from 37 regions of Russia. The duration of nOPV2 excretion ranged from 24 to 124 days post-vaccination. nOPV2 isolates contained 27 mutations per genome (0.36%) on average, with no critical genetic changes, which confirms the genetic stability of nOPV2 during field use. The possibility of epidemiologically significant poliovirus introduction into polio-free countries has been confirmed. The screening of special populations, including migrants, is required to maintain epidemiological well-being.

Introduction. The World Health Organization estimates that as of 2019, more than 296 million people were living with chronic hepatitis B virus (HBV) infection. The prevalence of HBsAg-negative, occult form of the disease in blood donors varies depending on the region of the world and the sensitivity of the methods of analysis used. Considering that the genetic diversity of viruses demonstrates space and time variations and taking into account that the genetic profile of isolates in key groups, which may turn into a source of the pathogen spread, is important for forecasting of the epidemiological situation, the attention should be given to identification of HBV genotypes currently circulating among regular blood donors in regions of the Russian Federation. The aim of this work was molecular and genetic characterization of HBV genomes identified in HBsAg-negative blood donors in the Ural Federal District. Materials and methods. The study material was 1400 plasma samples obtained from HBsAg-negative blood donors in Ural Federal District. The study included the testing for HBsAg, anti-HBs IgG and anti-HBcore IgG antibodies, HBV DNA. For all identified HBV DNA containing samples, sequencing and analysis of the nucleotide sequences of the complete HBV genomes were performed. Results. The prevalence of HBV DNA was 4.93%, including 4 (0.28%) cases of false occult hepatitis B. Among anti-HBcore IgG-positive samples, HBV DNA was found in 18.08% of cases, while in persons with detected HBV DNA the anti-HBcore IgG positivity rate was 46.38%. In 8.69% of the isolates, anti-HBs IgG antibodies and viral DNA were detected simultaneously in the absence of anti-HBcore IgG. Based on phylogenetic analysis, HBV subgenotypes distribution in HBsAg-negative blood donors was as follows: D3 53.62%, D2 21.74%, D1 18.84%, C2 5.8%. The high variability in the S, C, P regions of the virus genome in the examined group was shown. In all cases of HBsAg-negative chronic HBV infection identified in blood donors, viral sequences contained at least one amino acid substitution in positions, mutations in which are associated with immune escape. In 3 (4.35%) cases mutations in reverse transcriptase region of P gene that are associated with resistance to the following drugs were identified: lamivudine, telbivudine, entecavir. Mutations in the preCore/Core regions that contribute to the progression of liver disease were also identified. Conclusion. Occult HBsAg-negative chronic HBV infection poses a threat of HBV transmission through transfusion of blood and its components due to the extremely low viral load, which does not allow the virus to be detected using routinely used diagnostic kits. The situation can be exacerbated by the abundance and diversity of virus amino acid substitutions that we have identified, including immune escape mutations, drug resistance mutations, and mutations that contribute to the progression of the disease.

The Vietnam Ministry of Health (MOH) has intensified efforts in its aim to eliminate AIDS by 2030. Expanding the program for prevention of mother-to-child transmission (PMTCT) is a significant step towards achieving this goal. However, there are still HIV-exposed children who do not have access to PMTCT services, and some who have participated in the program but still contracted HIV. This study focused on assessing the prevalence and profile of HIV mutations among children under 18 months of age who had recently tested positive for HIV, while gaining insights into the implementation of early infant diagnostic (EID) tests. Between 2017 and 2021, 3.43% of 5854 collected dry blood spot (DBS) specimens from Vietnam’s Central and Southern regions showed positive EID results. This study identified a high prevalence of resistance mutations in children, totaling 62.9% (95% CI: 53.5–72.3). The highest prevalence of mutations was observed for NNRTIs, with 57.1% (95% CI: 47.5–66.8). Common mutations included Y181C and K103N (NNRTI resistance), M184I/V (NRTI resistance), and no major mutations for PI. The percentage of children with any resistance mutation was significantly higher among those who received PMTCT interventions (69.2%; 95% CI: 50.5–92.6%) compared with those without PMTCT (45.0%; 95% CI: 26.7–71.1%) with χ2 = 6.06, p = 0.0138, and OR = 2.75 (95% CI: 1.13–6.74). Mutation profiles revealed that polymorphic mutations could be present regardless of whether PMTCT interventions were implemented or not. However, non-polymorphic drug resistance mutations were predominantly observed in children who received PMTCT measures. Regarding PMTCT program characteristics, this study highlights the issue of late access to HIV testing for both mothers and their infected children. Statistical differences were observed between PMTCT and non-PMTCT children. The proportion of late detection of HIV infection and breastfeeding rates were significantly higher among non-PMTCT children (p < 0.05). Comparative analysis between children with low viral load (≤200 copies/mL) and high viral load (>200 copies/mL) showed significant differences between the mothers’ current ART regimens (p = 0.029) and the ARV prophylaxis regimen for children (p = 0.016). These findings emphasize the need for comprehensive surveillance to assess the effectiveness of the PMTCT program, including potential transmission of HIV drug-resistance mutations from mothers to children in Vietnam.

Confirming detected SARS-CoV-2-specific antibodies is necessary to reveal immune response in COVID-19 convalescent subjects as well as to conduct population studies by screening for specific antibodies to assess rate of COVID-19 prevalence. With this purpose St. Petersburg Pasteur Institute was the first in Russia to develop the ELISA kit for the quantitative determination of human IgG to the SARS-CoV-2 nucleocapsid (N-CoV-2-IgG PS). Arbitrary units (AU/ml) were used to assess the level of antibodies. The data shown in AU/ml were recalculated later to the international units (BAU/ml) in accordance with established the First WHO International Standard for anti-SARS-CoV-2 human Immunoglobulin. Comparing the data of the N-CoV-2-IgG PS calibration curve with those of the First WHO International Standard for anti-SARS-CoV-2 human Immunoglobulin revealed a complete inter-assay association (r = 0.999, R2 = 0.997) allowing to find that 1BAU/ml = 5.97 AU/ml. The aim of the study was to characterize the SARS-CoV-2 protein N Human IgG Quantitative ELISA Kit (N-CoV-2-IgG PS), compare quantitative and qualitative data of ELISA kits, assess a correlation between the binding antibodies to SARS-CoV-2 N proteins and the neutralizing antibodies against SARS-CoV-2. The data of correlation analysis of the 83 COVID-19 convalescent blood plasma samples a significant relationship between the antibodies quantitative values and titers SARS-CoV-2-specific antibody (r = 0.8436, R2 = 0.7802) as well as a moderate relationship between antibody concentration and positivity index (r = 0.6648, R2 = 0.3307), assessed by Chaddock scale. Comparing concentration of N-protein binding antibodies with neutralizing antibody titers level uncovered data consistency obtained by quantitative and virus microneutralization assays (r = 0.7310, R2 = 0.6527) used in parallel to analyze 80 blood plasma samples obtained from COVID-19 patients and convalescents. AUC under the ROC curve comprised 0.701 (P 0.0001) evidencing about a satisfactory informative value for N-CoV-2-IgG PS compared with microneutralization assay. In addition, the efficacy of the N-CoV-2-IgG PS was 95%, while the positive and negative prognostic value was 97% and 87%, respectively. The data obtained confirmed a correlation between N-protein binding antibody level and neutralizing antibody titer. Checking inter-assay agreement evidenced about acceptance for informativeness and efficacy of using N-CoV-2-IgG PS, thereby confirming an opportunity to apply the Kit to screen for SARS-CoV-2 N protein-specific IgG antibody level and assess seroprevalence in diverse population cohorts.

Introduction. As is currently known, the epidemic process in the Kaliningrad Region was mainly associated with the spread of the recombinant form of HIV-1 (CRF03_AB); however, regular HIV importations from other countries and continents has created favorable conditions for emergence and spread of various recombinant forms of the virus. The most complete information on the diversity of recombinant forms in the region is also necessary to understand the structure of drug resistance (DR). The aim of the study was to explore the HIV-1 genetic diversity in the Kaliningrad Region. Materials and methods. We studied 162 blood plasma samples obtained from patients from the Kaliningrad Region, both with confirmed virological failure of antiretroviral therapy (ART) and with newly diagnosed HIV infection. For reverse transcription and amplification of HIV genome fragments, diagnostic AmpliSense HIVResist-Seq. Results and discussion. The various recombinants between subtypes A and B (74%) were predominant in study group: recombinant was between CRF03_AB and subtype A (33.95%) and CRF03_AB-like (13.58%) were the most common. Among the pure subtypes of the virus, subtype A6 (16.67%). The circulation of subtypes B (3.70%) and G (1.23%) was also noted. Ninety-six patients (59.26%) were identified with at least one mutation associated with antiretroviral (ARV) drug resistance. Conclusion. The observed diversity of subtypes and recombinant forms of the virus implies that the new recombinants are actively emerging in the studied region, both between existing recombinant forms and pure subtypes, as well as between pure subtypes.

Primary immunodeficiencies (PID) are a heterogeneous group of hereditary diseases that lead to impaired immune defense. Often, the diagnosis cannot be made without identifying mutations that lead to the development of the disease. For many PIDs, there is no clear understanding of the etiology, pathogenesis, and genes involved. There is an obvious need to identify candidate genes potentially capable of leading to the development of PIDs.Hereditary angioedema (HAE) is a rare genetically determined disease, accompanied by recurrent edema of soft tissues and submucosal membranes, posing a threat to the life of patients. Diagnosis is based on the clinical presentation, family history, laboratory values of C1-esterase inhibitor, complement component 4, complement component 1q, antibodies to C1 and genetic testing for a number of mutations in the genes SERPING1, F12, PLG, ANGPT1, KNG1, MYOF, HS3ST6. However, pathogenesis may involve other genes in which the negative effect of mutations has not yet been studied. HAE is a non-monogenic disease that may involve an extensive network of genes. It seems important to determine the groups of the most probable candidate genes presumably involved in the development of pathology.Aim – to identify, using bioinformatics analysis, candidate genes for the development/pathogenesis of HAE and to reveal their biological context.The analysis was based on a group of genes, mutations in which are significantly associated with HAE: SERPING1, F12, PLG, ANGPT1, KNG1, MYOF, HS3ST6. To analised genetic and protein–protein networks and identify the biological context of the selected candidate genes, a number of web resources were used: HumanNetv3, GeneMania, FUMA GWAS in the GENE2FUNC mode.One hundred potential candidate genes in which mutations can be associated with HAE have been identified. The biological context of the identified genes was determined. The data of the biological context, genetic and protein-protein interactions made it possible to exclude a number of genes from the list of the most likely participants in pathogenesis and divide the remaining ones into groups with a greater or lesser potential for involvement. The group of the most likely HAO candidate genes includes PLAT, HRG, SERPINA1, SERPINF2, MASP2, GRB14, C1QBP, DOK2, KLKB1, F11, TEK, KLK10, KRT1, APOH, CPB2, F2.The results obtained can provide significant assistance in the study of the HAE molecular mechanism, as well as in the diagnosis and prognosis of the disease course. The identified candidate genes have the potential to serve as diagnostic biomarkers for patients with unexplained angioedema.The use of bioinformatic methods makes it possible to determine the list of candidate genes that are presumably involved in the disease pathogenesis or aggravate its course, and to obtain up-to-date information about the biological context of the identified genes. Understanding the genetic underpinnings and pathophysiology of PID may help define new diagnostic and therapeutic targets.

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.

Current review presents a brief overview of the immune system dysregulation during acute COVID-19 and illustrates the main alterations in peripheral blood CD4+ T-cell (Th) subsets as well as related target cells. Effects of dendritic cell dysfunction induced by SARS-CoV-2 exhibited decreased expression of cell-surface HLA-DR, CCR7 as well as co-stimulatory molecules CD80 and CD86, suggesting reduced antigen presentation, migratory and activation capacities of peripheral blood dendritic cells. SARS-CoV-2-specific Th cells could be detected as early as days 24 post-symptom onset, whereas the prolonged lack of SARS-CoV-2-specific Th cells was associated with severe and/or poor COVID-19 outcome. Firstly, in acute COVID-19 the frequency of Th1 cell was comparable with control levels, but several studies have reported about upregulated inhibitory immune checkpoint receptors and exhaustion-associated molecules (TIM3, PD-1, BTLA, TIGIT etc.) on circulating CD8+ T-cells and NK-cells, whereas the macrophage count was increased in bronchoalveolar lavage (BAL) samples. Next, type 2 immune responses are mediated mainly by Th2 cells, and several studies have revealed a skewing towards dominance of Th2 cell subset in peripheral blood samples from patients with acute COVID-19. Furthermore, the decrease of circulating main Th2 target cells basophiles and eosinophils were associated with severe COVID-19, whereas the lung tissue was enriched with mast cells and relevant mediators released during degranulation. Moreover, the frequency of peripheral blood Th17 cells was closely linked to COVID-19 severity, so that low level of Th17 cells was observed in patients with severe COVID-19, but in BAL the relative number of Th17 cells as well as the concentrations of relevant effector cytokines were dramatically increased. It was shown that severe COVID-19 patients vs. healthy control had higher relative numbers of neutrophils if compared, and the majority of patients with COVID-19 had increased frequency and absolute number of immature neutrophils with altered ROS production. Finally, the frequency of Tfh cells was decreased during acute COVID-19 infection. Elevated count of activated Tfh were found as well as the alterations in Tfh cell subsets characterized by decreased regulatory Tfh1 cell and increased pro-inflammatory Tfh2 as well as Tfh17 cell subsets were revealed. Descriptions of peripheral blood B cells during an acute SARS-CoV-2 infection werev reported as relative B cell lymphopenia with decreased frequency of nave and memory B cell subsets, as well as increased level of CD27hiCD38hiCD24 plasma cell precursors and atypical CD21low B cells. Thus, the emerging evidence suggests that functional alterations occur in all Th cell subsets being linked with loss-of-functions of main Th cell subsets target cells. Furthermore, recovered individuals could suffer from long-term immune dysregulation and other persistent symptoms lasting for many months even after SARS-CoV-2 elimination, a condition referred to as post-acute COVID-19 syndrome.

The relevance of the current epidemic situation of a new coronavirus infection is determined by new strains of the virus and the registration of cases of re-infection in COVID-19 survivors earlier. In this regard, the questions about the expediency and nature of vaccination of those who have been ill attract close attention, moreover it has affected the formation of the concept of “hybrid immunity”. The aim of this study was to analyze changes in the parameters of the immune system, reflecting their regulatory and functional potential, in response to the introduction of the peptide vaccine EpiVacCorona to persons who have suffered from the new coronavirus infection. To study the features of the formation of hybrid immunity, a retrospective analysis of the observation of 43 study participants was carried out. The inclusion criteria were data confirming COVID-19 in mild and moderate forms of the course in the period from six months to a year ago, a low level or absence of antibodies to the nucleocapsid protein SARS-CoV-2, a negative PCR result for the presence of the SARS-CoV-2 virus, the absence of comorbid pathology. The subpopulation composition, regulatory and functional potential of the immune system were determined by flow cytofluorimetry using a set of monoclonal antibodies corresponding to the goals. 21 days after the administration of a single dose of EpiVacCorona, antibodies to the vaccine peptide antigens were registered in all study participants at the highest coefficient of positivity values for the SARS-CoV-2-IgG-Vector test system used. In addition, there was a fourfold increase in the number of specific IgG to the N protein. A specific immune response to recombinant SARS-CoV-2 antigens was accompanied by a decrease in the circulation of the number of monocytes expressing TLR4, T helper cells expressing the interaction coreceptor with antigen-presenting cells, unconnected B memory with an increase in the number of B lymphocytes expressing the CD40 T-B coreceptor interaction molecule. The remaining differences in the functioning of the immune system identified in patients with COVID-19 before the vaccination in comparison with the control data have not changed. The differences consist in a decrease in the proportion of monocytes expressing HLA-DR, an increase in the expression of interaction molecules on T and B lymphocytes, an increase in the number of Treg, B1 cells, activated B lymphocytes with a decrease in the proportion of suppressor Breg and B memory. The totality of the presented data demonstrates that the COVID-19 infection that preceded vaccination in mild and moderate clinical course contributes to the formation of immunological memory, which made it possible to form a secondary immune response even to a single injection of peptide antigens of the virus.

Introduction. The problem of transfusion safety in relation to parenteral viral hepatitis still remains relevant. Viral hepatitis B (HB) remains the most common viral infection transmitted through transfusion procedures. One of the natural phases of chronic hepatitis B (CHB) is occult hepatitis B infection (OBI), characterized by an undetectable HBsAg (regardless of the other serological markers content) in the presence of hepatitis B virus (HBV) DNA in the liver tissue and an extremely low, up to undetectable, level of viral load in the blood. In the Republic of Guinea, as in most countries on the continent, the prevention of HBV transmission through transfusion is still based on HBsAg serological testing of donors only. In this connection, OBI remains as a potential threat to blood transfusion safety. Detection of HBV DNA is a reliable preventive measure against transmission of the virus from donors with HBsAg-negative HBV infection, especially in highly endemic regions. In this regard, the study was conducted to substantiate recommendations for improving blood safety against the background of significant HBV prevalence in the Republic of Guinea. The aim of the work was the evaluation of serological and molecular markers of HBV infection in blood donors in the Republic of Guinea. Material and methods. We examined 250 blood samples obtained from donors living in Conakry, Republic of Guinea. Samples were tested for the presence of serological (surface antigen, HBsAg; antibodies (ABs) to surface (anti-HBs IgG) and core (anti-HBc IgG) antigens) and molecular (DNA) markers of HBV infection. Results and discussion. The overall detection rate of hepatitis B markers was 83.2%; HBsAg was detected in 16.4% of all individuals. The high incidence of HBsAg in men (19.55%) compared to women (8.45%) was shown, the relative risk of HBV infection with the formation of HBsAg-positive chronic hepatitis B in males was also significantly higher. The prevalence of the HBV DNA in the study group was 30.4%, the OBI cases accounted for 15.6%. The prevalence of this form of the disease was shown in donors aged 30–49 years (24.78%), in the group of people younger than 30 years, the incidence was lower (8.73%), and at the age of over 50 years, OBI was not detected. Based on the phylogenetic analysis of 76 virus isolates, it was shown that genotype E prevails in the examined group (85.53%). Cases of pathogen DNA detection occurred in HBsAg-negative blood donors in the presence of anti-HBs IgG (n = 4), as well as in the simultaneous presence of ABs anti-HBs IgG and anti-HBc IgG (n = 7). The viral load exceeded 200 IU/ml in OBI samples. Escape mutations were detected by sequencing in each OBI sample, contributing to the virus escaping from diagnostic based on screening for HBsAg. Conclusion. Assessment of the prevalence viral hepatitis B markers in blood donors, determination of genotypes and clinically significant mutations of virus variants are necessary to ensure safe medical manipulations, control and prevention of the spread of this infectious agent.

Background. Humoral immunity requires interaction between B cell and T follicular helper cells (Tfh) to produce effective immune response, but the data regarding a role of B cells and Tfh in SARS-CoV-2 defense are still sparse. Methods. Blood samples from patients with acute COVID-19 (n = 64), convalescents patients who had specific IgG to SARS-CoV-2 N-protein (n = 55), and healthy donors with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 44) were analyses by multicolor flow cytometry. Results. Patients with acute COVID-19 showed decreased levels of memory B cells subsets and increased proportion plasma cell precursors compared to HC and COVID-19 convalescent patients, whereas for the latter the elevated numbers of virgin naïve, Bm2′ and “Bm3+Bm4” was found if compared with HC. During acute COVID-19 CXCR3+CCR6− Tfh1-like cells were decreased and the levels of CXCR3−CCR6+ Tfh17-like were increased then in HC and convalescent patients. Finally, COVID-19 convalescent patients had increased levels of Tfh2-, Tfh17- and DP Tfh-like cells while comparing their amount with HC. Conclusions. Our data indicate that COVID-19 can impact the humoral immunity in the long-term.

Introduction: The COVID-19 pandemic has become a serious challenge for humanity almost everywhere globally. Despite active vaccination around the world, the incidence proportion in different countries varies significantly as of May 2022. The reason may be a combination of demographic, immunological, and epidemiological factors. The purpose of this study was to analyze possible relationships between COVID-19 incidence proportion in the population and the types of SARS-CoV-2 vaccines used in different countries globally, taking into account demographic and epidemiological factors. Materials and methods: An initial database was created of demographic and immunoepidemiological information about the COVID-19 situation in 104 countries collected from published official sources and repository data. The baseline included, for each country, population size and density; SARS-CoV-2 testing coverage; vaccination coverage; incidence proportion; and a list of vaccines that were used, including their relative share among all vaccinations. Subsequently, the initial data set was stratified by population and vaccination coverage. The final data set was subjected to statistical processing both in general and taking into account population testing coverage. Results: After formation of the final data set (including 53 countries), it turned out that reported COVID-19 case numbers correlated most strongly with testing coverage and the proportions of vaccine types used, specifically, mRNA (V1); vector (V2); peptide/protein (V3); and whole-virion/inactivated (V4). Due to the fact that an inverse correlation was found between ‘reported COVID-19 case numbers’ with V2, V3, and V4, these three vaccine types were also combined into one analytic group, ‘non-mRNA group’ vaccines (Vnmg). When the relationship between vaccine type and incidence proportion was examined, minimum incidence proportion was noted at V1:Vnmg ratios (%:%) from 0:100 to 30:70. Maximum incidence proportion was seen with V1:Vnmg from 80:20 to 100:0. On the other hand, we have shown that the number of reported COVID-19 cases in different countries largely depends on testing coverage. To offset this factor, countries with low and extremely high levels of testing were excluded from the data set; it was then confirmed that the largest number of reported COVID-19 cases occurred in countries with a dominance of V1 vaccines. The fewest reported cases were seen in countries with a dominance of Vnmg vaccines. Conclusion: In this paper, we have shown for the first time that the level of reported COVID-19 incidence proportion depends not only on SARS-CoV-2 testing and vaccination coverage, which is quite logical, but probably also on the vaccine types used. With the same vaccination level and testing coverage, those countries that predominantly use vector and whole-virion vaccines feature incidence proportion that is significantly lower than countries that predominantly use mRNA vaccines.

According to the latest data released by UNAIDS, the global number of people living with HIV (PLHIV) in 2021 was 38.4 million, with 1.5 million new HIV infections. In different countries, a significant proportion of these cases occur in the adult fertile population aged 15–49 years. According to UNAIDS, Vietnam had a national HIV prevalence of 0.3% of the total population at the end of 2019, with approximately 230,000 PLHIV. The most effective way to prevent mother-to-child transmission of HIV is ART to reduce maternal viral load. HIV-infected pregnant women should undergo monthly monitoring, especially before the expected date of delivery. The aim of our work was to analyze subtypic structure and drug-resistant variants of HIV in pregnant women in Ho Chi Minh City. The study material was blood plasma samples from HIV-infected pregnant women: 31 women showed virological failure of ART, and 30 women had not previously received therapy. HIV-1 genotyping and mutation detection were performed based on analysis of the nucleotide sequences of the pol gene region. More than 98% of sequences genotyped as HIV-1 sub-subtype CRF01_AE. When assessing the occurrence of drug resistance mutations, genetic resistance to any drug was detected in 74.41% (95% CI: 62.71–85.54%) of patients. These included resistance mutations to protease inhibitors in 60.66% (95% CI: 47.31–72.93%) of patients, to NRTIs in 8.20% (95% CI: 2.72–18.10%), and to NNRTIs in 44.26% (95% CI: 31.55–57.52%). Mutations associated with NRTI (2) and NNRTI (8) resistance as well as PI mutations (12), including minor ones, were identified. The high prevalence of drug resistance mutations found in this study among pregnant women, both in therapeutically naive individuals and in patients with virological failure of ART, indicates that currently used regimens in Vietnam are insufficient to prevent vertical HIV infection.

Introduction. Vaccination contributed to reduce the incidence of acute hepatitis B in the territories of the North-West Russia. The urgency of this problem remains due to the high incidence of chronic hepatitis B. This accounted for the need to develop a hepatitis B elimination program in the district discussed that was approved in 2013 by the head of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing. Objective is to characterize the results of the program for the elimination of acute hepatitis B virus implemented in the North-Western Federal District. Materials and methods. The 2010–2020 incidence rate of acute and chronic hepatitis B virus (HBV) infection in the regions of the North-West Russia was carried out. To determine HBV genotypes and subgenotypes, 160 blood plasma samples from patients with acute hepatitis B were studied using molecular genetic methods (PCR, sequencing). The prevalence of latent hepatitis B in various population groups was assessed. The 2016–2020 hepatitis B vaccination coverage and relevant serological monitoring in adults was carried out. Results. While implementing the program, it was found that the incidence rate of acute hepatitis B in the district decreased by 4.5-fold, revealing in 2020 no cases of the disease in 5 regions, with incidence rate in the 6 subfederal units being lower than 1.0 per 100,000 population. Moreover, the incidence rate for chronic hepatitis B decreased by 2.6 times. The 2020 vaccination coverage of children under 17 and adults in all territories comprised more than 95% and 90%, respectively. In addition, it was shown the circulation of genotypes D and A of hepatitis B virus is dominated by genotype D (91.8%), subgenotype D2 (47.8%). The prevalence of latent hepatitis B among migrants was 6.5%, pregnant women — 4.9%, hemodialysis patients — 1.7%. Conclusion. Implementation of the program on elimination of acute viral hepatitis B in the territory of the North-West Russia contributed to raise in the vaccination coverage in adult population and lowered incidence rate of acute and chronic HBV infection.

Sarcoidosis is a polysystemic inflammatory disease of unknown etiology, morphologically related to the group of granulomatosis, with heterogeneous clinical manifestations and outcomes. Immune cells, in particular T helper cells, are attracted to lung tissue and/or other organs by chemokine gradients and play an important role in the granuloma formation. T helper cells migrate from peripheral blood to the tissues due to expression of CXCR3 chemokine receptor on their surface. It interacts, e.g., with CXCL9/MIG, CXCL10/IP- 10, and CXCL11/I-TAC. Our study was aimed for determining the levels of CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC chemokines in peripheral blood of the patients with sarcoidosis, depending on the features of their clinical course before administration of immunosuppressive therapy. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 52). In 37% (19/52), they exhibited acute clinical manifestations, and 63% (33/52) had chronic sarcoidosis. The control group included peripheral blood samples from healthy volunteers (n = 22). The chemokine concentrations (pg/ml) were determined by multiplex analysis using xMAP technology (Luminex), and Milliplex MAP test system (Millipore, USA). In the patients with sarcoidosis, significantly higher levels of chemokines were shown relative to healthy volunteers: CXCL9, 4013.00 pg/ml vs 1142.00 pg/ml (p < 0.001); CXCL10, 565.90 pg/ml vs 196.60 pg/ml (p < 0.001); CXCL11, 230.20 pg/ml vs 121.10 pg/ml (p = 0.018). Plasma concentrations of CXCL9 and CXCL10 were significantly increased both in blood samples from patients with acute and chronic sarcoidosis compared to healthy volunteers, p < 0.001. The level of CXCL11 chemokine was significantly increased only in the patients with chronic sarcoidosis, compared to the healthy volunteers: respectively, 251.50 pg/ml and 121.10 pg/ml (p = 0.044). The levels of this chemokine correlated with the activity of angiotensin-converting enzyme (ACE), with r = 0.374; p = 0.042. The ACE level in sarcoidosis is considered a clinical and laboratory index of the disease activity. In acute sarcoidosis, the level of CXCL11 chemokine was not significantly higher than in healthy individuals, whereas the CXCL9 chemokine content was significantly increased and correlated with ACE activity (r = 0.762; p = 0.037). The level of CXCL9 chemokine was significantly decreased in patients with signs of fibrosis as compared with fibrosis-free patients (1839.88 pg/ml vs 4375.52 pg/ml, p = 0.035). Significantly higher levels of CXCL9 were detected in cases of systemic sarcoidosis, i.e. 6036.84 pg/ml, as compared with 1927.44 pg/ml in the patients without these signs (p = 0.018). Evaluation of clinical and laboratory diagnostic characteristics for plasma chemokine levels in sarcoidosis patients allowed to assess their sensitivity and specificity. The respective values were as follows: in acute sarcoidosis: for CXCL9, 84% and 95%; for CXCL10, 84% and 95%; for CXCL11, 74% and 59%. In chronic sarcoidosis, the respective values for CXCL9 were 82% and 72%; for CXCL10, 91% and 77%; for CXCL11, 79% and 55%, respectively. Thus, the determination of plasma CXCL9, CXCL10, and CXCL11 chemokines in sarcoidosis allows of understanding their role in development of the disease, e.g., recruitment of T helper cells from peripheral blood to the lung tissue, and granuloma formation. Clinical and immunological comparisons of CXCL9 levels in the peripheral blood of patients and characteristics of the clinical course of sarcoidosis indicate to the role of this diagnostic parameter for assessing the disease activity, signs of lung fibrosis, and systemic manifestations in this disease.

Antinuclear antibodies (ANAs) represent a spectrum of autoantibodies targeted for various nuclear and cytoplasmic components of the cells. Indirect immunofluorescence assay (IIF) is the main detection method for “antinuclear factor”. A positive ANA test is usually reported as a titer and a pattern of fluorescence. The ANA patterns refers to the distribution of staining produced by antibodies that react with antigens located in nucleus and cytoplasm of HEp-2 cells. To standardize nomenclature and descriptions of the various fluorescence patterns of antinuclear factor (ANF), the Initiative of the International Consensus on ANA Patterns (ICAP) group was developed in 2014. The aim of ICAP is to promote consensus regarding nomenclature of ANA patterns, a microphotograph database, as well as classification depending on the employee skills. Information on the main characteristics, as well as specific clinical associations of the patterns is available at www.ANApatterns.org. In ANA classification trees, the patterns are indicated by the #AC (anticell pattern) alphanumeric code, being divided into nuclear, cytoplasmic and mitotic groups. Depending on the clinical significance and/or ease of recognition, this nomenclature focuses on the differences between the patterns described by specialists at competent and expert levels. Of the nuclear types, the most significant are homogeneous, speckled, dense fine-speckled, centromere, nucleolar, nuclear dots. The cytoplasmic types may be discerned into fibrillar, speckled, mitochondrial, Golgi, rods and rings. On leaders, behalf of the ICAP translation team is headed by the Full Member of Russian Academy of Sciences, Professor A.A. Totolian, under the auspices of the Russian Research Society of Immunologists. In this article, we present the Russianlanguage adaptation of the ICAP nomenclature, in order to ensure unification and standardization of ANA detection results in the patients with autoimmune diseases.

Sarcoidosis is an inflammatory disease of unknown etiology with damage to the lungs and other organs characterized by development of necrosis-free epithelioid cell granulomas. Granulomatous inflammation characterized by the activation of different immune systems cells, in particular T lymphocytes, and the cytokines production. Our study was aimed at investigating the characteristics of the cytokine profile of blood plasma in patients with sarcoidosis. We studied peripheral blood plasma samples of patients with sarcoidosis (n = 52). The control blood samples were taken from healthy volunteers (n = 22). The level of 46 cytokines (pg/ml) was determined, as follows: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL- 6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A, IFNα2, IFNγ, TNFα, TNFβ, IL- 1ra, IL-10, EGF, FGF-2, Flt3 Ligand, G-CSF, GM-CSF, PDGF-AA, PDGF-AB / BB, TGFα, VEGF-A, sCD40L, CCL2, CCL3, CCL4, CCL5, CCL7, CCL11, CCL17, CCL20, CCL22, CXCL1, CXCL8, CXCL9, CXCL10, CXCL11, CXCL13, CX3CL1. Significantly higher levels of interleukins and some proinflammatory cytokines were found in the patients with sarcoidosis, i.e., IL-3, 0.70 vs 0.20, p = 0.003; IL-4, 14.37 vs 3.15, p = 0.009; IL-5, 1.06 vs 0.89, p < 0.001; IL-12 (p70), 1.27 vs 0.56, p = 0.028; IL-17A, 1.48 vs 0.43, p < 0.001; IFNα2, 41.79 vs 25.04, p = 0.003; IFNγ, 4.13 vs 1.14, p < 0.001; TNFα, 21.67 vs 6.70, p < 0.001; anti-inflammatory cytokine IL-10, 1.03 vs 0.45, p = 0.019; growth factors: FGF-2, 40.08 vs 30.58, p = 0.008, G-CSF, 24.18 vs 8.21, p = 0.006, and VEGF-A, 42.52 vs 26.76, p = 0.048; chemokines: CCL3, 3.86 vs 1.33, p < 0,001; CCL17, 78.24 vs 26.24, p < 0.001; CCL20, 7.19 vs 5.64, p = 0.021; CCL22, 660.60 vs 405.00, p < 0,001; CXCL9, 4013 vs 1142, p < 0,001; CXCL10, 565.90 vs 196.60, p < 0.001; CXCL11, 230.20 vs 121.10, p = 0.018; CX3CL1, 56.99 vs 5.16, p < 0.001. Peripheral blood chemokine CCL11 levels were significantly lower in patients compared to the group of healthy volunteers: 77.58 vs 124.70, p = 0.022. The features of the cytokine profile in patients with sarcoidosis may indicate their important role in the processes of formation and outcomes of granulomas. These issues require an additional detailed study, comparison with phenotypes, differential course and outcomes of the disease.

Introduction. In late 2019 - early 2020, an outbreak of infection caused by a novel strain of beta coronavirus SARS-CoV-2 was reported. The World Health Organization defined the disease as coronavirus disease 2019 (COVID-19). In the Tyumen Region, the first case of COVID-19 was diagnosed on 31/1/2020. The source of infection was a female student who came from Jinan, Shandong province (China). The number and rate of cases were steadily increasing from the 16th week through 28th week in 2020. The highest rate was 36.87 cases per 100 thousand people. Afterwards, the cumulative incidence kept increasing gradually, but not as quickly.The purpose of the seroepidemiological study was to measure the level and to identify the structure of herd immunity against the SARS-CoV-2 virus among the population of the Tyumen Region during the rapid spread of the COVID-19 outbreak.Materials and methods. Volunteers for participation in the study were selected through questionnaire surveys and random sampling. The exclusion criterion was an active COVID-19 infection at the time of the survey. A total of 2,758 individuals were tested for SARS-CoV-2 specific antibodies. The age of the surveyed volunteers ranged from 1 year to 70 years and older.Results of the study. During the active phase of the COVID-19 incidence, the population of the Tyumen Region showed moderate (24.5%) seroprevalence of SARS-CoV-2. At the same time, the tests revealed a high (97.8%) rate of asymptomatic infection cases in seropositive individuals who had never been diagnosed with COVID-19 and did not have history of positive PCR test results or acute respiratory infection symptoms on the day of testing. The maximum level of herd immunity was identified in children aged 1-6 years (34.7%), which was significantly higher compared to the average level of seroprevalence in the entire cohort. In recovered COVID-19 patients, antibodies were detected in 68.2%. In individuals with positive PCR test results, antibodies were detected in 64%. Conclusion. The results of the assessment of the level of herd immunity against the SARS-CoV-2 virus are crucial for prediction of the development trend of the epidemic and for planning specific and non-specific COVID-19 prevention measures.

Here we review means of immunomodulatory therapy for coronavirus infection caused by SARS-CoV-2 (COVID-19). It has been appreciated that highly limited arsenal of relatively effective means and methods of prevention and treatment of the COVID-19 pandemic is available. The goal of our study was to analyze some therapeutic approaches based on available publications for COVID-19 treatment viewed from acting via innate immunity system. Convalescent plasma serotherapy represents one of the means with verified therapeutic efficacy that was accompanied with decreased viral load and relief of the disease symptoms. The drawback of serotherapy results from limited number of potential plasma donors and profound variety in amount of SARS-CoV-2-specific antibodies found in donor plasma. Another approach to COVID-19 therapy is based on using monoclonal antibodies engineered to target specific virus antigenic determinants, most often surface spike antigen. Antibodies blocking such antigen are able to prevent virus entrance into target cells and development of overt infection. On the other hand, there are monoclonal antibodies abrogating production or binding of excessive amounts of pro-inflammatory cytokines, such as IL-6, TNFα, etc., some of which (tocilizumab) have been already tested in COVID-19 therapy, whereas the remaining preparations are being currently investigated and tested. A certain breakthrough in COVID-19 therapy was provided by the well-known drugs chloroquine and dihydrochloroquine, which have proven to be effective as antiviral, anti-inflammatory and immunomodulatory means. Finally, a new multicomponent immunomodulatory preparation Cytovir-3 has been proposed already passed clinical trials and recommended for use in prevention and treatment of influenza and SARS and might have found its own niche in preventing COVID-19, as SARS-CoV-2 also belongs to the group of acute respiratory viruses. Thus, the arsenal of means for COVID-19 prevention and treatment contains the drugs for immunomodulatory therapy and prevention of immune-related disorders developing in response to invasion pathogenic viruses and lowering a risk of possible damage. Hence, correct and scientifically justified use of such remedies will increase overall effectiveness of fight against the coronavirus pandemic.

Low-affinity Fcγ-receptors that recognize the Fc portion of immunoglobulin (Ig) molecules, usually being in antigen-bound state, thus representing a link between innate and adaptive immunity. They play a significant role in inflammatory and infectious diseases. Among them, a separate FcγRII family (CD32) is discerned, which is characterized by transmission of intracellular signal independently of the common γ-chain, they have one α-chain containing two extracellular immunoglobulin-like domains. FcγRII receptors are present in almost all cells of the innate immune system: monocytes and macrophages, neutrophils, eosinophils, dendritic cells, as well as on B-lymphocytes and platelets. They perform two main functions: target recognition, facilitation of phagocytosis and destruction of antibody-opsonized cells by monocytes/ macrophages (including pathogenic cells). In parallel, the phagocytes are activated via the cytokine synthesis stimulation. The FcγRIIA (CD32a) and FcγRIIC (CD32c) activating receptors, like as FcγRIIB (CD32b) inhibiting receptors are present among the members of the FcγRII family. The low-affinity FcγRII receptors bind to IgG, with immune complexes being their natural ligands. High levels of immune complexes are usually found in both chronic viral infections and autoimmune diseases. There are shown polymorphic variants of the CD32a gene, which can affect the receptor function, and, thereby, causing susceptibility for different infections, influence the development of autoimmune diseases and primary immunodeficiencies. Activation of the CD32a receptor induces the production of pro-inflammatory cytokines, including TNFα and interferons, that are involved into inflammation in systemic lupus erythematosus, Kawasaki disease, Graves’ disease and rheumatoid arthritis. It has been shown that antibacterial activity of platelets is carried out via the CD32a receptor. The study of CD32a expression in people The CD32a receptor is considered a biomarker of cells that are a reservoir of HIV infection. At the present time, however, many questions remain regarding the mechanisms of CD32a expression of on HIV-infected cells and the role of CD32a in the formation of an HIV reservoir and/or development of appropriate resistance. In addition to HIV infection, the significance of FcγR receptors is shown in other infectious diseases, for example, with influenza and dengue virus infections. Better understanding of the CD32a structure and function will help to assess its role in immunopathogenesis of different conditions. This review focuses on the role of CD32a in development of the normal immune response in normal state and various diseases.

Purpose: The aim of this research is to develop an accurate and interpretable aggregated score not only for hospitalization outcome prediction (death/discharge) but also for the daily assessment of the COVID-19 patient's condition.Patients and Methods: In this single-center cohort study, real-world data collected within the first two waves of the COVID-19 pandemic was used (27.04.2020–03.08.2020 and 01.11.2020–19.01.2021, respectively). The first wave data (1,349 cases) was used as a training set for the score development, while the second wave data (1,453 cases) was used as a validation set. No overlapping cases were presented in the study. For all the available patients' features, we tested their association with an outcome. Significant features were taken for further analysis, and their partial sensitivity, specificity, and promptness were estimated. Sensitivity and specificity were further combined into a feature informativeness index. The developed score was derived as a weighted sum of nine features that showed the best trade-off between informativeness and promptness.Results: Based on the training cohort (median age ± median absolute deviation 58 ± 13.3, females 55.7%), the following resulting score was derived: APTT (4 points), CRP (3 points), D-dimer (4 points), glucose (4 points), hemoglobin (3 points), lymphocytes (3 points), total protein (6 points), urea (5 points), and WBC (4 points). Internal and temporal validation based on the second wave cohort (age 60 ± 14.8, females 51.8%) showed that a sensitivity and a specificity over 90% may be achieved with an expected prediction range of more than 7 days. Moreover, we demonstrated high robustness of the score to the varying peculiarities of the pandemic.Conclusions: An extensive application of the score during the pandemic showed its potential for optimization of patient management as well as improvement of medical staff attentiveness in a high workload stress. The transparent structure of the score, as well as tractable cutoff bounds, simplified its implementation into clinical practice. High cumulative informativeness of the nine score components suggests that these are the indicators that need to be monitored regularly during the follow-up of a patient with COVID-19.

Healthcare workers are much more likely to be infected with HIV and hepatitis viruses compared to the general population. Although healthcare workers are more aware of HIV and hepatitis viruses, several countries in Africa lack a comprehensive grasp of disease routes and transmission risks. The aim of this study was to assess the prevalence of the serological and molecular biological markers of HIV and viral hepatitis among healthcare workers in the Republic of Guinea. The study material was 74 blood serum samples collected from healthcare workers who received additional training at the Institute of Applied Biological Research of Guinea (IRBAG, Kindia, Republic of Guinea). The markers examined included HBsAg, HBeAg, anti-HBs IgG, anti-HBcore IgG, anti-HCV qualitative determination, anti-HEV IgM and IgG, anti-HAV IgM and IgG, and anti-HIV. For viral DNA and RNA detection, nucleic acids were extracted from blood serum, and viral presence was inferred using real-time PCR with hybridization fluorescence detection. A high prevalence of viral hepatitis B markers was shown, and significantly fewer cases of viral hepatitis C and HIV were detected. Almost all examined medical workers had anti-HAV IgG antibodies, but no antibodies to hepatitis E virus. Apparently, the identified markers depend on the general prevalence of certain pathogens in the region and are associated with the traditions and characteristics of the country’s residents.

Multiple sclerosis is chronic demyelinating disease of the central nervous system with autoimmune inflammation and accretive neurodegeneration. One of the characteristics of autoimmune inflammation in multiple sclerosis is a polyspecific intrathecal humoral immune response against neurotropic viruses (Measles, Rubella and varicella Zoster) called MRZ-reaction. This immune response is based on polyclonal activation of mature B lymphocytes in the central nervous system and intrathecal synthesis of antibodies to anamnestic antigens unrelated to viral replication in the central nervous system as well as serum antibody release. Immunoglobulins produced against neurotropic viruses are an integral part of the oligoclonal antibody pool in the cerebrospinal fluid. Because immunoglobulins can penetrate the blood brain barrier, not only serum and cerebrospinal fluid specific antibody indices are calculated, but also blood-brain barrier antibody permeability (Qalbumin, QIgG) are taken into account to assess their intrathecal synthesis. The aim of the study was to assess the informative value of the intrathecal antibodies against neurotropic viruses (MRZ-reaction) in multiple sclerosis. There were enrolled 60 patients divided into 2 groups: group 1 — 35 patients diagnosed with multiple sclerosis, group 2 — 25 patients with inflammatory and non-inflammatory disоrders of the central nervous system. Paired cerebrospinal fluid and serum samples were collected from all patients to measure level of oligoclonal IgG, immunoglobulin free kappa and lambda light chains, IgG index and specific antibodies indices, followed by assessing magnitude of MRZ-reaction. We found that the MRZ-reaction was the most specific test to diagnose multiple sclerosis. Intrathecally produced antibodies against neurotropic viruses were detected in 3 of 35 multiple sclerosis patients with lacking oligoclonal IgG antibodies. In addition, a relationship between MRZ-reaction and degree of EDSS disability was found in MS patients: peak EDSS score was reported in patients with intrathecally synthesized antibodies against 3 viral agents, whereas the minimum EDSS score — among MRZ-negative patients. Thus, assessing MRZ-reaction seems rational for confirming MS diagnosis in case of other negative laboratory tests (oligoclonal immunoglobulins and free kappa/lambda light chains in cerebrospinal fluid) allowing to improves diagnostic accuracy and evaluation of MS severity.

Allergen-specific diagnostics is carried out on the basis of the data collection from the patient’s family and personal history, skin test results, provocative tests and laboratory research methods. Methods for determining specific IgE antibodies (sIgE) play a key role in confirming the diagnosis and identifying the pathogenetic mechanism of an immediate-type hypersensitivity to an allergen. The purpose of the study was to evaluate the results of determining sIgE for allergens of cat epithelium, house dust mite D. farinae and birch pollen in the blood serum of patients suffering from respiratory allergy, by comparing two methods of ImmunoCAP Phadia and 3gAllergy Immulite, as well as determining whether the results of these test systems are in concordance with the results of skin tests in the patients. The serum samples were obtained from patients of St. Petersburg adult outpatient clinics, who suffered from respiratory allergies (n = 50). The samples were analyzed in parallel in two laboratories, with each of the laboratories using single test systems. The retrospective skin test results were obtained from twenty six of the fifty selected patients. The inter-method comparison was conducted by determining the concordance of positive and negative results, correlation and regression analysis of sIgE results for each allergen and ROC-analysis to compare the diagnostic specificity and sensitivity of test systems in relation to the results of skin tests. This study showed that, in terms of agreement and contingency of the results, the Immulite test system had a close relationship with the Phadia test system. Both analysis of classes and quantitative sIgE analysis showed a good positive correlation from 0.79 to 0.99 (p < 0.0001) between the two test systems for all three allergens. High accuracy of coincidence in terms of sensitivity, area under the ROC curves (AUC) and cut-off threshold in both test systems was obtained for the D. farinae allergen. For allergens of cat epithelium and birch pollen, some differences between test systems were observed, i.e., sensitivity and AUC values were significantly higher in Immulite than in Phadia assay for both allergens.Thus, the inter-method comparison gave almost equivalent binary and quantitative results of the determination of sIgE antibodies to cat, tick and birch allergens. Comparison of in vitro test results, and their correlation with skin tests showed that the cat and birch in vitro antibody testing with Immulite assay was more closely connected with skin test results, than Phadia assay system.

Chemokines are a special family of cytokines whose main function is to control cell migration; they are key players in the innate and adaptive immune responses. Directed chemotaxis of specific leukocyte subpopulations is necessary not only to maintain homeostasis, but also in development of some immunopathological conditions such as cancer, inflammation, infection, allergies and autoimmune disorders. Chemokines are pleiotropic molecules that are involved in physiological and pathophysiological processes. For example, the CXCR3 chemokine receptor is expressed on various cells: activated T and B lymphocytes, natural killers, eosinophils and neutrophils, dendritic cells, fibroblasts, endothelial and epithelial cells. Hence, CXCR3 and its ligands have a wide range of functional activity. CXCR3 ligands are the IFNγ-induced chemokines: CXCL9, CXCL10, CXCL11, and platelet-derived chemokines: CXCL4, CXCL4L1. All the CXCR3 ligands share common angiostatic properties due to lack of the Glu-Leu-Arg (ELR) motif. IFNγ-induced ligands of the CXCR3 are proinflammatory chemokines, they mainly recruit activated T cells and exert an effect on T cell polarization. Due to wide spectrum of biological activity, the ligands of CXCR3 receptor are involved in pathogenesis of various disorders, such as inflammation, infection, cancer, allergies and autoimmune disorders. In this review, we discuss the role of CXCR3 ligands in immunopathogenesis of various diseases, including the results of our studies in chronic hepatitis C, rheumatoid arthritis and pulmonary tuberculosis. Moreover, we have also discussed the potential laboratory diagnostic applicability of the chemokines in various diseases. This review illustrates a universal role of IFNγ-induced chemokines as mediators of immune responses in various diseases. The studies of CXCR3 ligands, their isoforms and receptors, interactions between themselves and with their receptors can provide a significant contribution to our understanding of the chemokine network. Understanding the system of IFNγ-dependent chemokines may have clinical implications, both for diagnostic tasks, and for therapeutic purposes.

Sarcoidosis is a disorder of unknown etiology characterized by development of necrosis-free epithelioid cell granulomas in various tissues. There are two main phenotypes of pulmonary sarcoidosis (PS): Lofgren’s syndrome (LS) is an acute form with favorable outcome, while non-Lofgren’s syndrome (nLS) is a chronic type of disease that can lead to pulmonary fibrosis in 20% of cases.Our study was aimed at investigating changes in the main cell-surface differentiation antigens on peripheral blood regulatory T cells (Tregs) from the patients with first diagnosed PS without treatment (LS, n = 11) and nLS (n = 46) compared to healthy volunteers (HC, n = 26).These indexes might be used as immunological markers for predicting severity of this disorder. Flow cytometry analysis of peripheral blood cell samples demonstrated that the nLS patients had decreased relative numbers of CD3+ cells vs healthy controls, as well as diminished CD3+CD4+ cells vs HC and LS patients. Furthermore, the relative and absolute Treg numbers were also decreased in nLS group vs HC (2.83% (2.47; 3.36) vs 3.33% (2.79; 3.84), p = 0.021), and 37 (29; 52) cells vs 50 (42; 65), p = 0.004, respectively) per one microliter of peripheral blood. Relative number of CD39-positive Тregs in chronic vs acute sarcoidosis patients was associated with 51.02% (38.20; 61.62) vs 48.64% (41.46; 63.72) that was significantly (p < 0.001 and p = 0.007, respectively) higher than in HC (39.52% (11.55; 46.34). We have found that “naïve” (CD45R0-CD62L+) Тregs did not significantly differ in percentage of CD39- and CD73-positive cells in all the groups tested. Moreover, CD45R0+CD62L+ Тregs in LS and nLS patients contained significantly more CD39-positive cells (69.66% (61.92; 79.34) and 67.62% (61.92; 79.34), respectively, compared to 47.55% (15.74; 65.32) in HC (p < 0.001 and p = 0.004, respectively). In case of CD45R0 + CD62LTregs able to exit from the circulation and migrate to the site of inflammation, an increased percentage of CD39-positive subset was noted only in patients with chronic sarcoidosis and HC (61.79% (55.12; 73.09) and 57.27% (16.03; 66.98), p = 0.006). Enhanced CD39 expression on Tregs seems to be related to chronic immune response, so that antigen elimination becomes impossible due to Treg overactivation, as shown in patients with sarcoidosis and some other chronic autoimmune and infectious disorders.

Background. The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic cells, and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding the role of CD8+ T cells in the acute phase of COVID-19 and post-COVID-19 syndrome are still limited. Methods.. Peripheral blood samples collected from patients with acute COVID-19 (n = 71), convalescent subjects bearing serum SARS-CoV-2 N-protein-specific IgG antibodies (n = 51), and healthy volunteers with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 46) were analyzed using 10-color flow cytometry. Results. Patients with acute COVID-19 vs. HC and COVID-19 convalescents showed decreased absolute numbers of CD8+ T cells, whereas the frequency of CM and TEMRA CD8+ T cells in acute COVID-19 vs. HC was elevated. COVID-19 convalescents vs. HC had increased naïve and CM cells, whereas TEMRA cells were decreased compared to HC. Cell-surface CD57 was highly expressed by the majority of CD8+ T cells subsets during acute COVID-19, but convalescents had increased CD57 on ‘naïve’, CM, EM4, and pE1 2–3 months post-symptom onset. CXCR5 expression was altered in acute and convalescent COVID-19 subjects, whereas the frequencies of CXCR3+ and CCR4+ cells were decreased in both patient groups vs. HC. COVID-19 convalescents had increased CCR6-expressing CD8+ T cells. Moreover, CXCR3+CCR6- Tc1 cells were decreased in patients with acute COVID-19 and COVID-19 convalescents, whereas Tc2 and Tc17 levels were increased compared to HC. Finally, IL-27 negatively correlated with the CCR6+ cells in acute COVID-19 patients. Conclusions. We described an abnormal CD8+ T cell profile in COVID-19 convalescents, which resulted in lower frequencies of effector subsets (TEMRA and Tc1), higher senescent state (upregulated CD57 on ‘naïve’ and memory cells), and higher frequencies of CD8+ T cell subsets expressing lung tissue and mucosal tissue homing molecules (Tc2, Tc17, and Tc17.1). Thus, our data indicate that COVID-19 can impact the long-term CD8+ T cell immune response.

Highly active antiretroviral therapy (HAART) is currently a combination of three (less frequently four) antiretroviral drugs; these target pathways involved in various stages of HIV replication in the body. Treatment failure is a problem facing doctors and patients using HAART. The most common cause of therapeutic failure is the development of HIV drug resistance. The emergence of resistance is associated with processes involving mutation occurring in the viral genome under the influence of evolutionary factors. Sequencing reactions were performed using the AmpliSens HIV Resist-Seq. Assembly of consensus sequences from fragments obtained during sequencing was carried out using Unipro UGENE softwar. Isolate genotyping was performed using the MEGA-X software with the Neighbor-joining algorithm. According to the analysis, 72.05% of patients had at least one significant mutation associated with drug resistance for the corresponding viral subtype. HIV-1 A6 remains the predominant HIV-1 genetic variant in Russia’s Northwestern Federal District. Among samples with drug resistance mutations, in all cases, mutations associated with pharmacological resistance to two or three drug groups were found. Given the high incidence of resistance mutations in patients on ineffective ART, surveillance of HIV-1 drug resistance, in both ART-receiving and ART-naive individuals, appears necessary. A lack of vigilance and control measures may lead to the spread of primary ART-resistant HIV strains.

Introduction: Primary immunodeficiencies (PID) are a group of rare genetic disorders with a multitude of clinical symptoms. Characterization of epidemiological and clinical data via national registries has proven to be a valuable tool of studying these diseases.Materials and Methods: The Russian PID registry was set up in 2017, by the National Association of Experts in PID (NAEPID). It is a secure, internet-based database that includes detailed clinical, laboratory, and therapeutic data on PID patients of all ages.Results: The registry contained information on 2,728 patients (60% males, 40% females), from all Federal Districts of the Russian Federation. 1,851/2,728 (68%) were alive, 1,426/1,851 (77%) were children and 425/1,851 (23%) were adults. PID was diagnosed before the age of 18 in 2,192 patients (88%). Antibody defects (699; 26%) and syndromic PID (591; 22%) were the most common groups of PID. The minimum overall PID prevalence in the Russian population was 1.3:100,000 people; the estimated PID birth rate is 5.7 per 100,000 live births. The number of newly diagnosed patients per year increased dramatically, reaching the maximum of 331 patients in 2018. The overall mortality rate was 9.8%. Genetic testing has been performed in 1,740 patients and genetic defects were identified in 1,344 of them (77.2%). The median diagnostic delay was 2 years; this varied from 4 months to 11 years, depending on the PID category. The shortest time to diagnosis was noted in the combined PIDs—in WAS, DGS, and CGD. The longest delay was observed in AT, NBS, and in the most prevalent adult PID: HAE and CVID. Of the patients, 1,622 had symptomatic treatment information: 843 (52%) received IG treatment, mainly IVIG (96%), and 414 (25%) patients were treated with biological drugs. HSCT has been performed in 342/2,728 (16%) patients, of whom 67% are currently alive, 17% deceased, and 16% lost to follow-up. Three patients underwent gene therapy for WAS; all are currently alive.Conclusions: Here, we describe our first analysis of the epidemiological features of PID in Russia, allowing us to highlight the main challenges around PID diagnosis and treatment.

The work presents data on forty-one patients with chronic hepatitis C (HCV, genotype 1), at different liver fibrosis stages. The studies were performed in the course of interferon-containing treatment regimens, i.e., pegylated interferon combined with ribavirin and pegylated interferon; ribavirin together with NS3/4A inhibitor of HCV serine protease. Concentrations of cytokines/chemokines (TNFα, CCL2/MCP-1, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/ITAC) were measured in blood plasma samples, using xMAP multiplex analysis. Flow cytometry studies were also performed in order to reveal cells with CCR6 and CXCR3 receptors in lymphocyte populations. The obtained results were analyzed using a statistical program package R. Results: 36 out of 41 patients achieved virological response, while 5 patients did not respond to the therapy. The responders were split into two groups, as follows: (1) liver fibrosis-free; (2) patients with fibrosis stages 1, 2 and 3. In the group of fibrosis-free patients, the decrease of CXCL11/ITAC concentration and the increase of TNFαwere observed, as well as increase of CTL CXCR3+ content by the 12th week of therapy and an increase of NK CXCR3+ by the end of treatment. In addition, this group exhibited a decrease in the CXCR3+ B lymphocyte contents at this timepoint. Concentrations of CCL2/MCP-1 during treatment were increased in the patients with different stages of liver fibrosis, as compared to baseline. By the end of therapy, an increase in the relative content of NK CXCR3+and TNK CCR6+ was also detected. The study confirmed a potential role of cytokines/chemokines TNFα, CCL2/MCP-1 and CXCL11/ITAC in activation of the cell-mediated immunity and elimination of the hepatitis C virus from the body. The results indicate that activation of T cellmediated immunity in both groups of the patients and reduction of B cells with CXCR3 receptor in the patients of first group is a positive prognostic factor showing efficiency of interferon therapy. Two of studied cytokines/ chemokines (TNFαand CCL20/MIP3α) differed in the groups of responders and non-responders at the start of therapy. Statistical evaluation of pre-treatment results has shown a tendency for differing concentration of TNFα, and CCL20/MIP3αamounts were significantly different for the patients of these groups. The plasma concentrations of CCL20/MIP3αin non-responders were > 4-fold higher than in responders to the therapy. Hence, the present study allowed us to propose the chemokine CCL20/MIP3α as a potential predictor of treatment outcomes in HCV infection.

Introduction. Since the detection of the first COVID-19 patient, 2 years have passed, during which more than 287,862,000 people have fallen ill globally, of which about 1.9% died. The implementation of SARS-CoV-2 control programs required efforts from almost all countries. An important direction in the fight against COVID-19 has been the formation of herd immunity, the main tool for managing the pandemic. Study goal. The aim of the study was to assess the seroprevalence of antibodies (Abs) to SARS-CoV-2 nucleocapsid (Nc) and receptor binding domain (RBD) in the St. Petersburg population during the COVID-19 pandemic. Materials and methods. A longitudinal cohort randomized monitoring study of Ab seroprevalence (SARS-CoV-2 Nc, RBD) was organized and conducted according to a unified methodology developed by Rospotrebnadzor with the participation of the St. Petersburg Pasteur Institute. For this purpose, a cohort was formed of 1000 volunteers who participated in all five stages of seromonitoring. The cohort was divided into seven age groups: 1–17; 18–29; 30–39; 40–49; 50–59; 60–69; 70; and older (70+) years. Seropositivity levels (Nc, RBD) were assessed by quantitative and qualitative enzyme immunoassays. During the second year of monitoring, some volunteers were vaccinated with the GamCOVIDVac (84%) or EpiVacCorona (11.6%) vaccines approved in Russia. Statistical processing was carried out using Excel 2010. Confidence intervals for shares and percentages (95% CI) were calculated using the method of A. Wald and J. Wolfowitz with adjustment (A. Agresti, B.A. Coull). The statistical significance of differences was calculated by z-test, using the appropriate online calculator (p < 0.05) unless indicated. Results. There was a trend toward an increase in Nc seropositivity in stages 1–3 of seromonitoring, with a decrease in stages 4–5 among children and adults. The share of RBD seropositive steadily increased during all five stages of seromonitoring. The most frequent finding was low anti-RBD Abs levels (22.6–220 BAU/mL). High Ab levels were recorded statistically significantly less frequently. Asymptomatic forms were observed in 84–88% of SARS-CoV-2 seropositive volunteers. By the fifth stage of monitoring, this indicator significantly decreased to 69.8% (95% CI: 66.1–73.4). The monitoring revealed a statistically significant increase in anti-RBD Abs alongside a statistically significant decrease in the proportion of Nc seropositives. This dynamic was especially characteristic of persons vaccinated with GamCOVIDVac. Conclusion. Prior to the use of specific vaccines, a seroprevalence of anti-Nc Abs was noted. After the introduction of the GamCOVIDVac vaccine in adults, a decrease in the level of anti-Nc Abs was noted due to an increase in the proportion of RBD seropositive persons.