This study examines the long-term effects of SARS-CoV-2 infection on immune status. Given the prolonged and profound immune dysregulation observed during acute SARS-CoV-2 infection, it remains to be determined whether these changes translate into subsequent immune system dysfunction in recovering individuals. In this sense, the aim of the study was to study the parameters of the immune system in patients who had undergone SARS-CoV-2 infection. 150 patients who underwent SARS-CoV-2 infection were examined according to 96 parameters using flow cytometry. A complete blood count was performed using a Medonic device (Sweden); ELISA method determined the levels of general and specific IgM, IgG, IgA, compliment fragments (JSC Vector-Best, Russia). The activity of the phagocytes was studied according to the generally accepted method. The study found that at least four phenotypes of immune system disorders are detected in patients. The first two phenotypes are related to the impairment of innate immune system factors and are associated with a decrease in the number of CD46+ and NK cells. It has been observed that a decrease in CD46+ persists for a long time in a significant number of recovered patients, highlighted by the impaired expression of this marker in various subpopulations of lymphocytes. The decrease in the level of natural killers was accompanied by a compensatory increase in the number of T lymphocytes, mainly due to T helpers and TNK lymphocytes, and the growth of total memory B cells. Two other identified phenotypes are characterized by damage to acquired immune response factors and are associated with damage to B cells and T cytotoxic cells. The relationship of such disorders with damage to hematopoiesis erythrocyte and platelet sprouts, which contribute to the appearance of hypoxia and possible violation of the blood coagulation system, has been shown. Therefore, the results obtained indicate a long-term pronounced damage to the immune system in postCOVID patients that requires immunocorrection of these disorders.

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.

Assessment of the state of the cells of the immune system in post-COVID patients currently remains little studied. The consequences of the influence of the virus itself, as well as drugs received by patients in the treatment of infection, on various body systems, including the immune system, contribute to disorders leading to post-COVID syndrome. The aim of the study was to study the level of cytotoxic T cells and features of immune system disorders in patients who had undergone SARS-CoV-2 infection. Materials and methods of research: 78 patients were examined 6 months after suffering COVID-19; studied 25 parameters of the blood system (general blood test), 50 parameters of the immune system, including T-lymphocytes, B-lymphocytes and their functional markers, NK, TNK cells, phagocytic part of the immune system, and humoral factors, including general and specific immunoglobulins and complement fragments. Results and discussion: when analyzing the results obtained, it was found that 44.8% of the examined individuals had a 1.7-fold decrease in the number of cytotoxic T-cells. This phenomenon was accompanied by a decrease in the level of T-lymphocytes in general, TNK-lymphocytes, some growth of T-helpers, an increase in the ratio of CD4/CD8 cells, levels of B-lymphocytes, due to B-total and B1, B2-lymphocytes of non-memory cells related to plasma cells (or otherwise the most actively producing immunoglobulins B cells). All these data indicate that in such patients, an immune response is formed to a greater extent according to the TH2 type (increased production of antibodies), and not according to the TH1 type (formation of cellular immune responses). In addition, in such patients, a violation of the TH1 response is observed and the likelihood of developing pathological processes associated with an inadequate response to viral antigens (including re-infection with the SARS-CoV-2 virus, exacerbations of chronic infections) increases. It is possible that the disorders we have identified in such patients may contribute to the occurrence or exacerbation of allergic and autoimmune processes in case of impaired functioning (hyperactivation) of the B-cell link of the immune system. All this requires further more detailed research, both in terms of further clinical observations of these patients, and the development of methods for correcting the identified disorders of the immune system.

To date, only minimal attention has been paid to assessment of immunity state in patients with post-COVID syndrome. Influence of the SARS-CoV-2 virus on various systems in the body, including the immune system, may contribute to the development of disorders causing different diseases. At the same time, the patients suffering from the COVID-19 complications, including hospitalization and isolation from their family members, experience severe psychological and social stress. In almost every fourth case, these factors lead to development of the s.c. post-COVID syndrome. The aim of the present study was to evaluate the numbers of NK cells, levels of cortisol and characteristics of immune system disorders in the patients who underwent SARS-CoV-2 infection. 78 patients were examined 6 months after suffering COVID-19. We have assessed 25 parameters of the blood system (general blood test), 50 parameters of immune system, i.e., counts of T lymphocytes, B lymphocytes and their functional markers, NK, T-NK cell subsets, phagocytic components of immune system, as well as factors of humoral immunity, including total and specific immunoglobulins and complement fragments. Our studies showed a sharp, three-fold decrease in the number of natural killers in more than 1/3 of the examined individuals. This decrease is accompanied by higher relative contents of T lymphocytes and T helper cells. The latter finding may be associated with a compensatory increase in T lymphocytes and dysregulation of the T cell link of immune system, thus requiring a more detailed study and, most likely, evaluation of the cytokine profile in such patients. Moreover, in some post-COVID patients, high levels of cortisol still persist, thus suggesting maintenance of chronic stress in these patients. Some changes in platelet counts are also important (increased levels of blood platelets and thrombocytocrit), which may promote later disorders of blood clotting system and development of thrombosis.

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.