The state of autoreactivity of innate immunity dominates in the pathogenesis of immunoinflammatory rheumatic diseases,  inducing non-infectious “sterile” inflammation. The  distinctive properties of this inflammation include  multiorgan affection and  recurrent clinical  course.  The  extracellular and intracellular “danger signals”  called DAMPs, seem to be a key factor  in progression of the inflammatory events.  These  factors  are  released  by the  loose  fibrous  connective tissue  in  the  course  of main  substance disorganization, as well as regulated and  accidental local  cell  death. In  immune/inflammatory rheumatic diseases,  the  DAMP-induced  patterns of  regulated cell  death  include   autophagy, apoptosis, necroptosis, pyroptosis  and  netosis.  Membrane and  cytosolic  PRR  receptors, interacting with  DAMPs, promote these DAMP-induced forms of regulated cell death. At the same time,  the DAMP-induced modes  of regulated cell death  are often combined with simultaneous reaction of PRR  receptors to the pathogens that preexist in dead cells. TLR-DAMP interaction activates  similar  signaling  pathways, adaptive  molecules, transcription factors, forming  the  same  pro-inflammatory  inflammasomes as with  TLR-PAMP interaction. In  these  processes, the  antigen-presenting function of dendritic cells is expressed  to the  maximal extent.  Given  the  important role of infections as etiological factors  in immunoinflammatory rheumatic diseases,  these  processes  may be the key factor  inducing the phenomenon of antigenic cross-presentation. Interactions of DAMPs with PRR receptors of innate immunity cells cause the formation of a DAMP-mediated vicious circle. At the same time, increased levels of proinflammatory DAMPs, both  in situ and  in systemic  circulation, leads,  via the  PRR-DAMP interactions, to incresing  number of cells prone  to regulated cell death  and to even more  pronounced tissue  damage. In  turn,   these  processes   significantly   increase   the  levels  of  pro-inflammatory DAMPs in tissues,  thus causing  progression of “sterile” inflammation to immunoinflammatory rheumatic diseases.  The signaling  pathways, adaptive  molecules, transcription factors,  and  pro-inflammatory  inflammasomes have been identified in all types of regulated cell death  induced by PRR-DAMP interaction. The available research results  allow us to determine appropriate targets  which  may be subjected to pharmacological correction. In this respect, significant  progress  has been  made  in search  for medicinal tools  of regulating inflammation in SLE,  RA, Sjogren’s syndrome, SSD,  etc. Of sufficient  importance are both evaluation of serum DAMP levels as diagnostic and prognostic biomarkers, along with their  determination for assessing treatment efficiency  in immunoinflammatory rheumatic diseases.

Research data presented in the article are based, mainly, on the concept that thymus, together with bone marrow represent the central organ of immune system being the source of all T cell populations that, following their migration from thymus to periphery, participate in development of immune response to any antigens of viral, bacterial and tissue origin, and to any allergens. This difference is principal, as opposed to the bone marrow which produces other members of immune response, i.e., dendritic cells, macrophages, B cells. E.g., the bone marrow also generates the cells which migrate to thymus where they undergo differentiation to the T cells. Over last 50 years, a plethora of data was accumulated on the leading role of immune system  in pathogenesis of virtually all socially significant human diseases affecting the modern mankind, including infectious and malignant disorders, atherosclerosis, autoimmune and allergic diseases. Moreover, current studies show that the aberrant functions of different T cell populations play the leading role in pathogenesis of these diseases. These T cell disturbances in peripheral areas of different organs are proven to develop, mainly in the thymic area. Hence, thymus is a producing organ of T cells with altered functional activities which promote pathogenetic changes in these disorders. Currently, the entire set of immunotherapeutic approaches is aimed for correction of disturbances among the same T cells subpopulations at periphery, without taking into account thymic mechanisms which have induced these disturbances before their emigration from thymus. One should, therefore, develop novel methods and approaches to correct these alterations within thymic area.

The thymus is now considered a derivative of the immune system being, to greater extent, its central organ. Immunodeficiency states and immune dysregulation also depend on the quality of the thymus, which may be determined both genetically and by fetopathic approach as well as due to the possibility and mode of its intravital injuries, age-related involution over different periods of life. Not accidentally, there are various morphometric bipolar states of the thymus gland in the pediatric population (3-7%), whereas its size may be sufficiently larger or smaller than the reference variable values. In certain cases, the phenomenon of thymomegaly (for example, in newborns) is considered a result of genetic errors (neuro-endocrine-immune syndrome with thymomegaly) induced by the mutated Hox genes. This syndrome may also be associated with congenital heart disorders. Moreover, the excessive morbidity in respiratory infections (commonly, viral by their etiology) among young children with bipolar thymus conditions remains the subject of sharp discussions. Some works assessing immune status in the children subjected to forced thymectomy, e.g., during heart surgery, yielded quite controversial results, even in cases of subtotal removal of thymus gland.

Dialectically, the concepts of “morphology” and “organ function” could not be separated from one another. The morphometric transformations in organs (even transient ones) occuring within the range of > 95 and < 5 percentiles, should be almost always underlied by a certain pathomorphosis which require verification of their causes and origin. Even today, however, the assessment of thymus pathomorphology in the deceased children is not always critical, being often descriptive. This situation is, probably, associated with extreme complexity of thymic morphology assessment. The final point seems to be not set in the discussion about immunodeficiency states or immune dysregulation among children with bipolar thymus transformations. This is due to current absence of reliable immune-mediated biomarkers, the limited availability of genetic diagnostics in primary immunodeficiency conditions, and a decreased interest of clinical science in the issues of bipolar conditions of the thymus gland at the early age, in the absence of longitudinal observations in this category of patients, etc. In this article, the authors attempt to draw attention of researchers to this problem.

Thymic gland (thymus) represents a huge mystery for biology, medicine (primarily immunology), including pediatric issues. Complexity of the study is determined by the multiplicity of integral connections of thymus with other components of immune system, neuroendocrine, hematopoietic systems, connective tissue, different organs and cells which provide appropriate barrier function. Discerning the direct thymic function from this continuum, or determining specific role of molecular factors (neuropeptides, growth hormone, etc.) upon the immune physiology represents a problem which is not yet resolved. In this review article dedicated to the current state of the problem, we consider the morphological and functional relationships between thymus, neuroendocrine system and, in particular, with hormones of the somatotropic axis. These interactions may also manifest by clinical heterogeneity which may be associated with impaired morphogenesis (organogenesis) at a very early stage of embryogenesis; namely, under the influence of gene family that determine the fate of each segment of the embryo-Hox genes which control the expression of other, functionally interconnected genes. Previously, T lymphocytes produced by the thymus and brain neurons have been shown to express the same antigen (Thy antigen), which was considered a specific antigen of T lymphocytes. A common molecular language, mediated by the molecules of intercellular interaction, was revealed which is used for the signal exchange between the cells, tissues and organs regulating the three mentioned systems (nervous, endocrine and immune). The interest of pediatricians in this field is associated with definite concept of human ontogenesis, from birth to elderly age, with thymic gland playing the main role, since antenatal period to early childhood. The main line of reasoning in this research area is not only theoretical, but also important from practical point of view. Since any critical involution of the thymus is accompanied by reduced number of produced and exported cells, a hormone-based therapy may be an alternative strategy to restore the organ by increasing thymocyte proliferation, and exporting mature T cells to peripheral lymphoid organs. Great opportunities have been opened in clinical immunology due to development of effective epistemological methods, e.g., genetic knock-out, transgenic animal models with human stem cell transfer, transplantation of hematopoietic and immunopoietic cells in primary and secondary immunodeficiencies, immune cell malignancies, autoinflammatory diseases, and, finally, infections of the immune system.

Microalgae from the freshwater basins and seas are a valuable source of broad-spectrum biologically active substances that can affect the cells of immune system and their functional state. Cytokines are involved in all vital processes proceeding in the living cells (proliferation, maturation, differentiation, apoptosis/ necrosis). A study was performed in order to assess the effects of standard food formula for experimental animals supplemented with oil extract of microalgae from various systematic groups upon the levels of cytokines in blood serum, culture media conditioned by immunocytes, as well as kidney and liver tissues. The standard food was impregnated in oil extracts of microalgae (C. vulgaris, Coelastrella sp., A. platensis, C. closterium, and P. purpureum). In control series, the food was impregnated with pure vegetable oil. The animals were fed these foods for 12 days. Blood, spleen and thymus were taken to isolate immunocytes, kidneys and liver, and dimethyl sulfoxide extracts of the cells were produced. The conditioned media of splenocytes and thymocytes were obtained by adding concanavalin A (0 and 10 μg/ml) to the cultured cells. The levels of NO, IL-1β, IL-10, TNFα, and NO were determined in serum, conditioned media, and tissue extracts. In serum, the influence of microalgae on the levels of IL-1β and TNFα was revealed. Activation of immunocytes in experimental groups was followed by changes in IL-1β, TNFα and IL-10 production. Changes of cytokine and NO levels were revealed in liver and kidney extracts in experimental groups. Thus, microalgae extracts of various systematic groups affect the levels of cytokines in blood serum, cultural media conditioned by splenocytes and thymocytes, kidney and liver tissues.

Inflammatory process is at the heart of artificial (artificial) purulent-inflammatory diseases of soft tissues (APDST), which may lead to the development of phlegmon and abscesses at the site of invasion within a three-day period. The study of the cytokine status of rats with APDST allows us to evaluate the dynamics of inflammation markers and assess the peculiarities of the pathological course in artificial model of inflammation. The experiment was carried out on 126 white Wistar rats divided into 3 groups: (1) the main group (n = 57), where the laboratory model of APDST was used; (2) a comparison group (n = 58), in which the rats were injected with a mixture of opportunistic bacterial strains isolated from pure cultures of human oral fluid, i.e., S. epidermidis, S. mitis, S. salivarius at the titer of 9lg (CFU) per 1 ml injected together with a mixture of 2.5% hydrocortisone acetate emulsion (20 mg per 100 g of animal body weight), and dexamethasone solution at the dose of 0.5 mg; (3) control group (n = 11), where the animals were injected with 0.9% sodium chloride solution in a volume of 0.3 ml, together with a mixture of 2.5% hydrocortisone acetate emulsion at the rate of 20 mg per 100 g of body weight, and dexamethasone solution at the dose of 0.5 mg. Blood cells were studied using the Mindray DC-2800 Vet Auto Hematology Analyzer automated rat blood test system. The dynamics of pro-inflammatory cytokines: tumor necrosis factor (TNF), interleukin-1β (IL-1β), interleukin-6 (IL-6), antiinflammatory cytokines: interleukin-4 (IL-4), interleukin-10 (IL-10) was assessed by enzyme immunoassay. To predict the course of inflammation towards complications, or resolution of the inflammatory process, the ratio of pro-inflammatory to anti-inflammatory cytokines was used, with normal ratio considered an estimated average of the cytokine ratio for the control group. When analyzing results of this experimental study, the nature of cellular inflammatory response was assessed in dynamics, and its relationship with inflammation markers was determined. All animals of the main group developed soft tissue phlegmon within 3 to 7 days from the beginning of the experiment, and their mortality rate was 100%. In comparison group, the abscesses developed in 82.8% of cases on the day 12 to 15 from the start of the experiment, without any deaths observed. The ratio of pro- and anti-inflammatory cytokines in the main group increased 8-fold already by the end of the 1st day, the comparison group was characterized by the absence of significant differences from the control group. The highest levels of pro-inflammatory cytokines were recorded in the main experimental group on the days 12 to 15.

Despite advances of modern medical science, the consequences associated with management of complications in type 1 diabetes mellitus (DM1) in children and adolescents represent a serious problem. Common development of microvascular diabetic complications (retinopathy, neuropathy, kidney damage) still remains a sufficient obstacle for achieving high quality of life and social adaptation in the young patients, thus promoting studies of immune mechanisms involved in genesis of microvasculature damage under the conditions of dysmetabolic abnormalities associated with DM1. Our goal was to assess the role of altered cytokine balance in blood serum in development of microangiopathies in adolescents with DM1.

140 adolescent patients with type 1 diabetes aged 14-18 years were examined being divided in 2 groups: group I included the patients with glycated hemoglobin (HbA1c) level of > 9.0% (n = 65), and group II which included adolescents with HbA1C level of ≤ 9.0% (n = 75). Each group was divided into subgroups: Ia (n = 50) and IIa (n = 38) included adolescents with diabetic retinopathy, nephropathy or neuropathy, whereas groups Ib (n = 15) and IIb (n = 37) were without microvascular complications. The control group consisted of 36 adolescents with normal body weight, without carbohydrate metabolic disorders, and family history of diabetes mellitus. Determination of TNFα, IL-1β, VCAM-1, fractalkine levels in blood serum was performed by enzyme immunoassay using test systems “RayBiotech” (USA), “BIOSCIENCE” (USA).

Development of microangiopathies in adolescents with different glycemic control is associated with increased serum concentration of the factors involved in neoangiogenesis and vascular wall remodeling, i.e., TNFα, IL-1β, VCAM-1, compared with control group (p < 0.05), and a statistically significant decrease in fractalkine level in adolescent patients with either complicated, or uncomplicated DM1. The study allowed us to suggest that occurrence of microvascular complications in adolescents with DM1 is associated with impaired immune response tending for altered cytokine balance towards Th1 type, enhanced intercellular interactions, imbalance of bioregulatory molecules, contributing to development of inflammatory immunoregulatory state. The revealed patterns of laboratory markers, along with assessment of metabolic indices, will enable personalized approaches to early diagnostics of microvascular complications in adolescents with DM1 and prevent their further progression.

Varicocele is a varicose dilation of pampiniform plexus veins in testicular gland, considered a special case of phlebopathy. With varicocele, there is impaired venous outflow via the left renal vein from the veins of testicular pampiniform plexus. Increased hydrostatic pressure leads to failure of the wall tone of the testicular vein, valvular venous insufficiency with dilation of the local venous system. Vasodilation requires integrity of endothelial layer, and its damage resulting from hydrodynamic stress is a trigger for development of an inflammatory response and production of cytokines. Pro-inflammatory cytokines have a pronounced damaging effect on endothelial cells, leading to endothelial dysfunction and chronic inflammation. Angiogenesis is an important characteristic of inflammatory disorders. Both inflammation and its controlling mechanisms employ many common factors, including IL-1β, IL-6, IL-8, TNFα. The purposes of our study were: to determine the dynamics of the pro- and anti-inflammatory cytokine levels, and VEGF contents in blood serum of adolescents with left-sided varicocele in order to assess the severity of inflammatory reaction of the vessels in the pampiniform plexus as well as prognosis of angiogenesis and remodeling of the testicular veins. We examined 100 adolescents with left-sided varicocele II-III degree and 30 adolescents without varicocele, who made up the comparison group. All adolescents (14 to 17 years old) underwent determination of IL-1β, IL-6, IL-8, TNFα, IL-4, IL-10, VEGF levels in blood serum at a frequency of 1 year, depending on the degree of varicocele, terms after varicocelectomy.

Statistically higher levels of pro-inflammatory cytokines were found over different age periods in adolescents with varicocele, as well as increased levels of anti-inflammatory cytokines, which may suggest an inflammatory process in testicular veins associated with varicocele. Higher levels of pro-inflammatory cytokines were found in patients with grade III varicocele compared with patients with grade II condition, but without statistically significant differences. In adolescents prior to varicocelectomy, significantly higher levels of cytokines were determined, which persisted over the postoperative period. Based on these results, one may assume that, in phlebopathy, the inflammatory process persists until surgical correction, and adaptation to the changed blood flow after surgery does not take time. VEGF values remain approximately similar over the observation period, and, probably, the changes of the vessel walls occur due to inflammatory process, and not to activation of angiogenesis

In varicocele disorder, an inflammatory status is observed in the altered testicular venous plexus, being more pronounced in grade III varicocele and affected by subsequent surgical correction.

Diabetic retinopathy is a serious microvascular complication of diabetes mellitus with chemokines playing an important pathogenetic role. However, the studies of chemokines in lacrimal fluid of the patients with diabetic retinopathy and type 2 diabetes mellitus (T2DM) are rarely performed. The aim of the study was to analyze the content of chemokines in lacrimal fluid of patients suffering from diabetic retinopathy and T2DM. When determining the concentration of chemokines in the lacrimal fluid, two clinical groups were formed: the main group of 56 elderly patients suffering from diabetic retinopathy and T2DM, and a control group of 48 age-matched persons with T2DM, however, without diabetic retinopathy. The diagnosis of diabetic retinopathy was performed after comprehensive ophthalmological examination using various modern techniques and applying the criteria of the All-Russian Association of Ophthalmologists “Diabetes mellitus: diabetic retinopathy, diabetic macular edema”. The chemokine levels in the lacrimal fluid were determined in the morning on the MAGPIX device (USA). The changed contents of chemokines was shown in lacrimal fluid of patients with diabetic retinopathy and T2DM, in comparison with patients suffering from T2DM in absence of diabetic retinopathy. In elderly patients with diabetic retinopathy and T2DM, a decreased content of GROα/ CXCL1, RANTES/CCL5 and MIP-1α/CCL3 was revealed in lacrimal fluid, at a statistically significant difference as related to controls. At the same time, the content of GROα/CXCL1 chemokine in lacrimal fluid was decreased most significantly, (38.24±2.57 in the main group versus 13.61±1.74 pg/mL in the comparison group). The level of RANTES/CCL5 decreased to 0.92±0.16 pg/mL versus 1.69±0.18 pg/mL (p < 0.001); MIP-1α/CCL3, to 2.06±0.71pg/mL versus 3.79±0.64 pg/mL, respectively. However, the proportion of chemokines in the lacrimal fluid of patients with diabetic retinopathy and T2DM was significantly inceased in  all  cases.  This  finding  concerns  MCP-1/CCL2,  IP-10/CXCL10,  and  SDF1α/CXCL12.  The  content  of IP-10/CXCL10 in lacrimal fluid increased to maximal values of 38.24±2.57 pg/mL in the patients with diabetic retinopathy and T2DM compared with 13.61±1.74 pg/mL in patients with diabetes mellitus without diabetic retinopathy, MCP-1/CCL2 to 742.34±0.89 pg/mL compared to 633.72±0.64 pg/mL, respectively; SDF1α/ CXCL12, to 264.78±7.82 pg/mL compared to 213.49±6.08 pg/mL. In addition, the interrelations between studied chemokines in patients with diabetic retinopathy and type 2 diabetes mellitus are more pronounced than in comparison group as confirmed by large number of correlations in the main group. The results obtained expand the knowledge on the effects of chemokines in lacrimal fluid upon development of diabetic retinopathy.

Hereditary angioedema (HAE) is a genetically determined disease characterized by recurrent attacks of edema affecting the subcutaneous and/or submucosal layers of tissue, face, lips, neck, extremities of the body,  oral cavity,  intestine and/or larynx. In the latter case, the disease becomes life-threatening.    The majority of HAE cases are associated with decreased levels of C1 (C1-esterase inhibitor), there are also descriptions of HAE with dysfunctional C1 inhibitor and HAE with normal C1 inhibitor. In the first and second variants, mutations in the C1NH gene are the cause of the disease. HAE with normal quantitative  and functional levels of C1-inhibitor has the same clinical manifestations but with mutations in other genes, including F12, PLG, ANGPT1, KNG1, MYOF, and HS3ST6. Currently, mutations in the HS3ST6 gene remain poorly understood; only one missense mutation (p.Thr144Ser, rs746467957) associated with the development of HAE has been described.

The aim of our work was to study new mutations in the HS3ST6 gene and analyze in silico their prognostic nature and clinical significance for the development of hereditary angioedema.

The material was whole blood samples obtained from 13 patients with symptoms of hereditary angioedema without reduced levels and function of C1-INH.

Whole exome sequencing of patients, bioinformatic analysis of HS3ST6 gene mutations using a number of databases and Web resources to predict the effect of mutations on the protein and assess the conservatism of the positions of the mutations detected was involved in study methods.

Mutations in the HS3ST6 gene were identified in four patients, including two cases with two mutations simultaneously. Application of bioinformatic analysis allowed us to obtain new data on four missense mutations in the studied gene. Potential pathogenetic significance was determined for three of them. The mutation NC_000016.9:g.1962132G>A (p.A163V) is most likely to be involved in pathogenesis of HAE by indirect disruption of heparan sulfate O-sulfation directly within the protein. The NC_000016.9:g.1962024G>A mutation (p.P199L) appears to lead to the development of the disease through disruption of docking with SDC2 heparan sulfate. In the NC_000016.9:g.1962046C>T (p.A192T) mutation, destabilization of the 192 amino acid position next to PAPS, may contribute to disruption of heparan sulfate O-sulfation through disruption of protein functional activity and, therefore, catalysis transfer of sulfo group to heparan sulfate syndecan-2. Thus, in all three cases, the formation of HAE appears to be possible due to disruption of the O-sulfation steps of heparan sulfate syndecan-2.

Considering that in silico methods offer new opportunities to assess the pathogenetic significance of mutations, the application of bioinformatic analysis can contribute to a detailed investigation of the causes of hereditary angioedema. The present work convincingly demonstrates that rare mutations in the HS3ST6 gene may be involved in the pathogenesis of HAE and provoke edema due to increased bradykinin release.

The pathogenesis of severe coronavirus infection COVID-19 is associated with activation of immune system, cytokine storm, impaired blood clotting, microvascular thrombosis, organ ischemia and multiple organ dysfunction syndrome. The role of various lymphocyte subpopulations in COVID-19 is still debated. The aim of our study was to analyze the subpopulational profile of peripheral blood lymphocytes in COVID-19 patients as compared with healthy donors.

The study included 20 COVID-19 patients (11 males and 9 females,) and 26 healthy donors. Average age of the patients was 52 and 56 years, respectively. Clinical examinations were performed by standard laboratory methods. Peripheral blood lymphocytes were isolated in the Ficoll gradient. The cells were stained with antibodies to specific antigens of main lymphocyte populations, endothelial cells, and apoptotic cell markers. The analysis was performed by flow cytometry. The results showed that all patients had elevated C-reactive protein (14- to 35-fold), ferritin (1.2- to 13-fold), D-dimers (1.2- to 90-fold). 55% of men had a decrease in the absolute number of lymphocytes, in women this index was at the low normal limit. Cytometric analysis showed that, among peripheral blood lymphocytes, the proportion of functional cells expressing the CD45 marker ranged from 2 to 12% in 70% of patients, as compared with 80-99% among the donors. The proportion of CD45⁺ lymphocytes significantly correlated with the level of hemoglobin, but not with the levels of inflammatory biochemical markers. Among the functional lymphocytes of patients, there was a decrease in the proportion of CD3⁺, CD4⁺, CD8⁺T cells, increased proportion of natural killer CD56⁺ and the apoptotic (AnnexinV⁺) cell contents, but the proportion of CD19 and HLA-DR⁺B cells was not changed. Analysis of the lymphocyte (LC) subpopulations that did not express CD45 marker showed that this fraction contained different lymphocyte subsets with reduced expression of CD4, CD8, CD19, CD56 etc. in the blood of patients and donors. Higher percentage of endothelial cells expressing CD62P marker made the difference between patients and donors.

Laboratory determination of lymphocyte subsets in blood samples of COVID-19 patients does not reflect the real severity pattern of the disease, thus requiring studies of the CD45-expressing functional cell populations.

Assessment of viral load levels in various biological samples taken from the respiratory tract can be an indicator of an ongoing process of active viral replication and may be used to monitor severe respiratory viral infections. The study of the relationship between SARS-CoV-2 viral load and immunological laboratory parameters is an important step in the search for clinical markers of COVID-19.

The aim of this research was to quantify viral load in patients with COVID-19 and to identify the relation-ship between viral load and changes in the parameters of the cellular component of the immune system.

A laboratory examination was carried out on 74 patients diagnosed with COVID-19, they were divided into 3 groups based on the severity of the disease: mild, moderate, severe. Total viral load in clinical samples was determined by the number of SARS-CoV-2 RNA copies per 100 copies of the reference RNaseP gene.     A comprehensive assessment of the cellular component of the immune system was performed using flow cytometry and direct monoclonal antibodies, and the IL-6, and C-reactive protein concentrations were determined.

We revealed a relationship between the development of serious clinical conditions in the patients with COVID-19, and the levels of viral load. High levels of viral RNA in biological samples correlate with main indicators of the T cell component of the immune system associated with disease severity. In a subgroup of patients with an extremely high viral load, strong positive correlations were found between the relative numbers of cytotoxic lymphocytes (CD3⁺CD8⁺), activated T lymphocytes (CD3⁺HLA-DR⁺), as well as absolute and relative numbers of activated B lymphocytes and NK cells (CD3-CD25⁺).

Laboratory monitoring of the cellular component of the immune system, along with the assessment of viral loads, should improve  early assessment of clinical condition in the patients with COVID-19. Changes   in expression levels of activation markers on immune cells can be potentially viewed as indicators of recovery during COVID-19.

The studies on humoral immune response in the individuals who have undergone COVID-19 and vaccinated with anti-COVID vaccines allows us to assess the  development  of  “hybrid”  immunity,  which contributes to understanding the mechanisms of its formation from the effector phase to the step of immunological memory. We assessed the relative and absolute contents of B cell populations and subpopulations, development of humoral immunity in the patients who suffered with COVID-19 of varying severity being thereafter vaccinated with “KoviVak” and “Sputnik V”. The study involved volunteers (age 47.3±14.5 years) who beared COVID-19 asymptomatically (n = 32), at moderate severity (n = 21), or had severe form of the disease (n = 12), then being vaccinated with “KoviVak” and “Sputnik V” 6-9 months after their recovery. The groups of vaccinated persons consisted of those who beared severe disease being vaccinated with “KoviVak” (n = 6) or “Sputnik V” (n = 6); moderate cases, vaccinated with “KoviVak” (n = 10) and “Sputnik V” (n = 11); asymptomatic cases vaccinated with “KoviVak” (n = 10) and “Sputnik V” (n = 22). We have determined relative and absolute numbers of B lymphocytes (CD45⁺CD19⁺), B1 lymphocytes (CD45⁺CD5⁺CD19^-CD27^-), B2 lymphocytes (CD45⁺CD19⁺CD5^-CD27^-), total population of memory B cells (CD45⁺CD19⁺CD5^-CD27⁺), non-switched (CD45⁺CD19⁺IgD⁺CD27⁺), and switched (CD45⁺CD19⁺IgD^-CD27⁺) memory  B  cells;  mature  naive   B   lymphocytes   (CD45⁺CD19⁺CD27^-IgD⁺),   plasmoblasts   (CD45⁺CD19⁺ CD38⁺⁺⁺IgD^-CD27+),   as  well as presence of IgG to S(RBD)-SARS-CoV-2 protein.

We have found that the humoral immunity among survivors of COVID-19 of varying severity is expressed for up to nine months. The largest number of volunteers who raised antibodies to SARS-CoV-2 S-protein was registered in the group of seriously ill patients. As soon as 1 month after “Sputnik V” vaccination and until the end of the observation, all the examined subjects in this group became seropositive. 4-5 months after injection of this vaccine, specific immunoglobulins were present in all patients who had asymptomatic or average-severity infection. All volunteers who received “KoviVak” had antibodies to the COVID-19 viral S protein from the beginning to the end of the study. Vaccination, especially with “KoviVak”, contributed to the highest increase, both in relative and absolute numbers of memory B lymphocytes in asymptomatic patients. Less pronounced changes in the content of B lymphocytes in COVID-19 patients who had severe and moderate clinical course may be associated with higher levels of these cells prior to injection of the vaccines. A positive correlation was found between the number of memory B cells and presence of immunoglobulins to the S protein SARS-CoV-2 in all examined patients.

Despite all efforts of the world community, the COVID-19 pandemic remains one of the main epidemiological challenges of our time. Even with its widespread distribution, the infection may have certain local features due to social, geographic, and climatic factors. Objective: to study collective immunity to SARS-CoV-2 in the population of the Republic of Tajikistan.

A cross-sectional, randomized study of herd immunity was carried out according to a program developed by Rospotrebnadzor and the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The ethics committees of the corresponding entities approved the study: Tajik Ministry of Health and Social Protection; and the St. Petersburg Pasteur Institute (Russia). Based on questionnaire results, 4,022 people were selected, representing 0.15% (95% CI: 0.14-0.15) of the total population randomized by age and region. In subsequent laboratory analysis, 3682 people took part. The distribution and quantitative content of antibodies (Abs) to viral nucleocapsid (N Ag) and receptor binding domain (RBD Ag) were determined by ELISA. When questioned, a history of SARS-CoV-2 vaccination was indicated by 69.7% (95% CI: 68.2-71.2) of the volunteer cohort. Vector vaccines were most frequently used (50.6%; 95% CI: 48.7-52.5), with whole-virion inactivated preparations in second place (23.0%: 95% CI: 21.4-26.6) and mRNA vaccines in third place (21.0%; 95% CI:19.4-22.6).

The cohort (n = 3682) featured 27.5% men and 72.5% women. The overall seroprevalence was 98.5% (95% CI: 97.7-99.2) in men and 99.4% (95% CI: 99.0-99.6) in women (differences statistically insignificant). Overall seroprevalence in the cohort was 99.2% (95% CI: 98.8-99.4) and ranged from 97.2 to 100% in certain subgroups. Asymptomatic seropositivity in the whole cohort was 98.4% (95% CI: 97.6-99.1). As a result of a mandatory vaccination program introduced in Tajikistan under a COVID-19 Emergency Project, the level of herd immunity among vaccinated individuals reached 99.5% (95% CI: 99.1-99.7), which is similar to the level reached in the cohort as a whole.

The epidemic situation that developed in Tajikistan by mid-March 2022 was characterized by an almost absolute level of herd immunity, as evidenced by an absence of detected overt COVID-19 cases since the end of February (2022).

Reports on antibody titers following CoronaVac administration are still scarce, particularly when it comes to the post-vaccination effectiveness of CoronaVac in the Indonesian population. The purpose of  this study is to determine the efficacy of COVID-19 vaccination by comparing the IgG levels against the S1 subunit of SARS-CoV-2 RBD after the first and second vaccinations. The researchers collected venous blood samples from participants after they received the CoronaVac 600 SU/0.5 mL vaccine at two different intervals (14 days and 28 days). Blood was drawn twice (after the first and second vaccinations) and tested for antibodies (positive antibody detection value of 50 AU/mL). Paired data were analyzed by using either the Wilcoxon test (numerical) or the McNemar test (categorical). The median IgG1 levels in the 14-day interval between vaccine doses were 64.40 AU/mL and IgG2 levels were 886.10 AU/mL. Meanwhile, the median IgG1 level was 146.10, and IgG2 level was 688.00.AU/mL in the group with a 28-day interval between vaccine doses. After the first vaccination, 60.00 % of study subjects had positive IgG levels, which increased to 98.57% after the second vaccination. Following the full-dose vaccination, all participants had higher antibody levels, and considered significant. The effect was stronger in the group that received the vaccine at 14-day intervals. CoronaVac has also been shown to increase the prevalence of detectable antibody positivity in study participants.