Granulocyte-macrophage colony-stimulating factor (GM-CSF) belongs to the group of growth cytokines (hematopoietins) that regulate proliferation and differentiation of myeloid lineage cells. Recently, a lot of new data have accumulated, indicating the presence of a number of previously unknown biological effects in GM-CSF and synthetic peptides of its active center, which open up new prospects for their wide clinical use.The review outlines current understanding of the structure, functions, and mechanisms of GM-CSF action and concerns the structure of its receptor. The GM-CSF producer cells are characterized, as well as target cells (effector cells) responding to this cytokine are also presented. The known mechanisms of intracellular signaling involved into the GM-CSF/receptor interaction are described. The main pleiotropic effects of this cytokine as a factor of hematopoiesis and an immunostimulating agent are characterized. The previously known and recently found immunobiological effects of this cytokine, its recombinant forms and synthetic analogues of its active center are discussed.Participation of GM-CSF in hematopoiesis and differentiation of myeloid cells, the effects of this cytokine on the functional activity of immunocompetent populations (lymphocytes, macrophages, neutrophils, dendritic cells) and tissue cells were characterized. The influence of GM-CSF on the development and course of infectious and inflammatory processes, its role in the creation of combined vaccines is reviewed. Clinical data on usage of GM-CSF and its recombinant forms in hematology, immunology, oncology, reproductive medicine and in the treatment of systemic autoimmune processes and infectious diseases are presented.The recently discovered immunobiological properties of synthetic peptides derived from active center of GM-CSF are summarized, indicating that they exhibit immunotropic and hematopoietic effects, as well as antimicrobial activity against Gram-negative and Gram-positive bacteria, viruses, and tissue repair (effect on the rate of wound healing), which is not typical to the whole GM-CSF molecule. We discuss the prospects for clinical applications of synthetic GM-CSF analogue (ZP2 peptide), and an opportunity of creating new cosmetics and pharmaceuticals with combined immunostimulating, antimicrobial and reparative properties on its basis.The review expands the view on potential usage of cytokine therapy in the treatment of various infectious and non-infectious diseases in humans, and is addressing a wide range of specialists working in the field of allergology and immunology, infectology and regenerative medicine.

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.

Treatment of chronic viral infections accompanied by permanent virus persistence in the target epitopes of the oral cavity, skin, urogenital tract is complicated by virtual lack of available drugs exerting combined systemic virulicidal and immunomodulatory effects. Here we demonstrate clinical and immunological efficacy of combined therapy in treatment of Epstein–Barr virus (EBV)-associated chronic infections. The aim of the study was to evaluate the clinical and immunological efficacy of combined etiopathogenetic therapy using the Acegram cosmetic product in patients with EBV-associated chronic infections. Materials and methods. There were enrolled 40 patients monitored before treatment as well as 20 patients followed up after combination therapy (cycle therapy consisted of oral valaciclovir (Valtrex) applied at dose of 500 μg twice a day for 10 days, glucosaminylmuramyldipeptide (Licopid) — 10 mg 2 twice a day for 10 days, topical irrigation for mucous membranes with granulocyte-macrophage colony-stimulating factor active center-derived peptide (Acegram-spray) 3 times a day for 10 days. If necessary, treatment courses were repeated 20 days after the onset. All patients were examined for the presence of EBV genomes in the oral fluid and blood using the qualitative and quantitative polymerase chain reaction (PCR) using the DNA technology test system (Russia) on a DT-Lite device prior treatment and 30, 60 days post-therapy time points. In addition, serum samples were analyzed for level of class G immunoglobulins specific to the EBV nuclear and capsid antigens by using enzyme immunoassay (test systems manufactured by CJSC Vector Best, Russia) as well as immune status (clinical methods, enu flow cytometry evaluation of the phagocytic activity of neutrophils, ELISA method). Results. Use of single or two course combination therapy in subjects with fully eradicated EBV carriage associated with reversed clinical symptoms was accompanied by recovered immune system status (T and B cells, T-helper cells, CD3+ CD25+ cells, phagocytosis parameters). A non-invasive approach proposed for controlling virus elimination in the oral fluid by using polymerase chain reaction method may serve as to objectively monitor therapeutic efficacy.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to global morbidity and mortality. Some patients fully recover from COVID-19, whereas around 45% subjects suffer from various persistent symptoms (fatigue, cognitive impairment, impaired thermoregulation, skin diseases, etc.) for at least four months after SARS-CoV-2 infection regardless of disease severity. Such persistent post-infection effects are known as long-COVID, post-acute effects of COVID-19, or post-COVID state. SARS-CoV-2 infection is accompanied by damage to the innate immune system. Considering the role of natural killer cells and the activation of the complement system in COVID-19 as well as the regulatory properties related to CD46 and its potential involvement in cell virus entry, we found necessary to study immune system parameters associated with impairment of these innate immune cues on various leukocyte subpopulations in post-COVID patients. We studied 92 immune system parameters, including: pan-leukocyte markers for gated lymphocytes, phenotyping of T cells, T-helper inducers, cytotoxic T-lymphocytes, NK- and TNK-cells, T-regulatory cells/suppressors, B-lymphocytes, including B-memory cells, activated helpers, early activation of lymphocytes, activated T-lymphocytes, and late lymphocyte activation markers. Levels of total IgM, IgG, IgA, specific IgM, IgG to coronavirus COVID-19, C1-inhibitor, C3a, and C5a complement components were measured by enzyme immunoassay using Multiscan FC Thermoscientific enzyme immunoassay analyzer (China) and Vector Best reagent kits (Russia). A complete blood count was conducted to study 25 parameters: leukocyte, erythrocyte, and platelet hematopoietic lineages as well as the quantitative and qualitative composition of hematopoietic lineages. Our study results showed that in some patients, six months after suffering from COVID-19, there was a decrease in the level of NK cells (48%) and CD46+pan-leukocyte marker cells (64.5%). A decrease in NK cell levels was accompanied by increased level of total T- and B-lymphocytes, and altered platelet and erythroid hematopoietic lineages. In patients with reduced CD46 expression on T-lymphocytes, both their total count and NK cell count were significantly reduced. Our data also suggest that CD46 might be potentially involved in development of SARS-CoV-2 infection and the post-COVID state. Thus, in 50–65% of patients who have experienced SARS-CoV-2 infection, damage to the innate immune system persists after six months being accompanied by impaired erythroid and platelet hematopoietic lineages. The data obtained indicate a need for using immunocorrective therapy in such patients.

SARS-CoV-2 virus can induce immune system disorders in post-COVID patients, which may persist for an extended period beyond the acute phase of the disease. Therefore, the search for immunocorrection approaches to address the detected disorders is a significant challenge in clinical immunology. This study aimed to investigate the impact of a synthetic peptide derived from the active center of GM-CSF on the immune system of patients with post-COVID immunopathological syndrome. A total of 21 patients who previously suffered with SARS-CoV-2 infection were included in the study. Flow cytometry was used to analyze various immune cell populations, including panleukocyte markers for gated lymphocytes (CD45⁺ and CD46⁺), T lymphocytes (CD3⁺), helper inducers (CD3⁺, CD4⁺), cytotoxic T lymphocytes (CD3⁺, CD8⁺), TNK cells (CD3⁺, CD56⁺), natural killer cells (CD3^-, CD56⁺), B lymphocytes (CD3^-, CD19⁺), activated helper cells (CD3⁺, CD4⁺, CD25⁺), and activated T lymphocytes (CD3⁺, HLA-DR). Moreover, IgA, IgM, IgG antibodies specific to SARS-CoV-2, phagocytosis and NBT activity of neutrophils, and complement fragments C1q, C3a, and C5a were assessed. The results demonstrated that topical application of the synthetic peptide derived from the active center of GM-CSF (Acegram-spray) upon mucous membranes significantly influenced the functional bactericidal activity of neutrophils (NBT-activity), increased the percentage of T helper cells, and elevated the C3a complement fragment. These findings indicate that the synthetic peptide primarily affects innate immunity factors. However, no significant differences were observed in other immune system parameters. Therefore, the development of therapeutic approaches for post-COVID patients with impaired immune systems may require a search for additional immunomodulators that target T, B, and NK cells. Further research is needed to explore the effects of various immunomodulators on the immune system of post-COVID patients.

Serological methods have become especially in demand during the SARS-CoV-2 pandemic, as they have high specificity, ease of implementation, good speed and relatively low cost.People with symptoms of COVID-19 were found to be statistically significantly more likely to test positive for IgM and IgG. The positivity coefficient was also significantly higher in the group of people with symptoms of coronavirus infection. The distribution of the density of positive ELISA results for all types of antibodies was multimodal in both groups of patients, with many peaks that differ both in density values and in time periods of their detection. When analyzing the multimodal distribution of the obtained seroprevalence results for the period from 06/01/2020 to 01/18/2022, it was found that in people at risk, peaks of increased density of positive for IgM results appeared earlier, which may reflect the initial spread of infection in asymptomatic patients. The smallest differences in the time of occurrence of peaks of high density of seropositive ELISA results between groups was determined for IgA — from 2 to 8 days. This may be due to the relatively short seroconversion time for this type of antibody. In general, using serological methods for diagnosing COVID-19, it is possible to assess the prevalence of coronavirus infection in different cohorts of the population, as well as to study in more detail the features of the immune response to SARS-CoV-2.