Glucosaminylmuramyl dipeptide efficacy in post-COVID-19 patient rehabilitation treatment.

The COVID-19 pandemic has altered people's lifestyles around the world. Prevention of recurrent episodes of the disease and mitigation of its consequences are especially associated with effective post-COVID-19 rehabilitation in patients. The aim of the study was to evaluate the effects of the drug Likopid (glucosaminylmuramyl dipeptide, GMDP) for post-COVID-19 rehabilitation in patients. Material and methods. Patients who recovered from mild to moderate COVID-19 (n=60, mean age 54+/- 11.7 years) were randomized into the observation group (n=30, 15 men and 15 women) who received 2 courses of Licopid (1 mg twice a day) and the comparison group (n=30, 15 men and 15 women). Analysis of the phenotypic and functional characteristics of the innate immune cellular factors was carried out before the start of immunomodulatory therapy, immediately after the end of the course, and also after 6 months observations. In order to assess the quality of life of all patients, we used the SF-36 Health Status Survey and the Hospital Anxiety and Depression Scale questionnaires. Results. During assessing the effect of immunomodulatory therapy on the parameters of innate immunity of patients at the stage of rehabilitation after COVID-19, an increase in the protective cytolytic activity of CD16+ and CD8+Gr+ cells, as well as a persistent increase in TLR2, TLR4 and TLR9 expression was found, which indicates the antigen recognition recovery and presentation at the level of the monocytic link of the immune system. The use of GMDP as an immunomodulatory agent resulted in an 8-fold reduction in the frequency and severity of respiratory infections due to an increase in the total monocyte count. As a result of assessing patients' quality of life against the background of the therapy, a positive dynamic in role functioning was revealed in patients. In the general assessment of their health status, an increase in physical and mental well-being was noted during 6 months of observation. The comparison group showed no improvement in the psychoemotional state. Discussion. The study demonstrated the effectiveness of GMDP immunomodulatory therapy in correcting immunological parameters for post-COVID-19 rehabilitation in patients. The data obtained are consistent with the previously discovered ability of GMDP to restore impaired functions of phagocytic cells and induce the expression of their surface activation markers, which in turn contributes to an adequate response to pathogens. Conclusion. The study revealed that the correction of immunological parameters with the use of GMDP in COVID-19 convalescents contributed not only to a decrease in the frequency and severity of respiratory infections, but also to an improvement in the psycho-emotional state of patients, and a decrease in anxiety and depression.Copyright © Eco-Vector, 2023. All rights reserved.

Glucosaminylmuramyl dipeptide efficacy in post-COVID-19 patient rehabilitation treatment.

The COVID-19 pandemic has altered people's lifestyles around the world. Prevention of recurrent episodes of the disease and mitigation of its consequences are especially associated with effective post-COVID-19 rehabilitation in patients. The aim of the study was to evaluate the effects of the drug Likopid (glucosaminylmuramyl dipeptide, GMDP) for post-COVID-19 rehabilitation in patients. Material and methods. Patients who recovered from mild to moderate COVID-19 (n=60, mean age 54+/- 11.7 years) were randomized into the observation group (n=30, 15 men and 15 women) who received 2 courses of Licopid (1 mg twice a day) and the comparison group (n=30, 15 men and 15 women). Analysis of the phenotypic and functional characteristics of the innate immune cellular factors was carried out before the start of immunomodulatory therapy, immediately after the end of the course, and also after 6 months observations. In order to assess the quality of life of all patients, we used the SF-36 Health Status Survey and the Hospital Anxiety and Depression Scale questionnaires. Results. During assessing the effect of immunomodulatory therapy on the parameters of innate immunity of patients at the stage of rehabilitation after COVID-19, an increase in the protective cytolytic activity of CD16+ and CD8+Gr+ cells, as well as a persistent increase in TLR2, TLR4 and TLR9 expression was found, which indicates the antigen recognition recovery and presentation at the level of the monocytic link of the immune system. The use of GMDP as an immunomodulatory agent resulted in an 8-fold reduction in the frequency and severity of respiratory infections due to an increase in the total monocyte count. As a result of assessing patients' quality of life against the background of the therapy, a positive dynamic in role functioning was revealed in patients. In the general assessment of their health status, an increase in physical and mental well-being was noted during 6 months of observation. The comparison group showed no improvement in the psychoemotional state. Discussion. The study demonstrated the effectiveness of GMDP immunomodulatory therapy in correcting immunological parameters for post-COVID-19 rehabilitation in patients. The data obtained are consistent with the previously discovered ability of GMDP to restore impaired functions of phagocytic cells and induce the expression of their surface activation markers, which in turn contributes to an adequate response to pathogens. Conclusion. The study revealed that the correction of immunological parameters with the use of GMDP in COVID-19 convalescents contributed not only to a decrease in the frequency and severity of respiratory infections, but also to an improvement in the psycho-emotional state of patients, and a decrease in anxiety and depression.Copyright © Eco-Vector, 2023. All rights reserved.

Clinical and immunological characteristics of the postcovid period in patients with moderate-severe COVID-19 who received therapy with the inclusion of an IL-6 receptor antagonist

Introduction. Significant progress in clinical research has led to a better understanding of the pathogenesis of COVID-19, contributing to its more effective therapy. The revealed key role of IL-6 in the development and intensification of the <<cytokine storm>>, which has received reliable pathophysiological and pharmacological justification, supports the use of therapeutic strategies aimed at IL-6 or its receptor. Nevertheless, the changes that occur in the immune system after COVID-19 are of interest for a better understanding of the mechanisms of the formation of postcovid syndrome in patients receiving therapy with the inclusion of IL-6 receptor antagonists, its pathogenesis and the search for targets for further therapeutic effects. The aim of the study - to study the clinical and immunological parameters of patients who underwent a moderate-severe variant of COVID-19 and received therapy with the inclusion of IL-6 receptor antagonist during treatment and 6 months after discharge/recovery. Material and methods. 30 hospitalized patients were examined with the diagnosis: COVID-19, moderate-severe form;complication: bilateral polysegmental pneumonia. The comparison group consisted of practically healthy donors (30 people). The dynamics of laboratory parameters (general clinical, biochemical and immunological) were evaluated against the background of therapy with IL-6 blockers at discharge, as well as 6 months after discharge from the hospital, in addition, the quality of life was assessed 6 months after the COVID-19. Results. Postcovid syndrome in patients who have undergone COVID-19 in a moderate-severe form manifests itself in a number of symptoms - decreased appetite, weakness, sleep disorders, depression, headache, shortness of breath, cough, tachycardia, dizziness. In addition, there is an exacerbation of chronic diseases that requires correction in planned therapy. 6 months after discharge from the hospital, there is an increase in CRP and fibrinogen levels, which most likely also reflects the deterioration of the course of concomitant pathology. There is an increase in the level of T-lymphocytes, as well as a decrease in the level of B-lymphocytes. Conclusion. Patients who had COVID-19 require dynamic follow-up. In patients with a moderate-severe form of COVID-19 who received complex therapy with the inclusion of monoclonal antibodies to IL-6 receptors, dexamethasone, antiviral therapy, anticoagulants, oxygen therapy, there are dysregulatory processes in the immune system that persist 6 months after recovery. Copyright © 2022 Meditsina Publishers. All rights reserved.

Features of postinfectious immunity formation in a patient with common variable immune deficiency and severe COVID-19 course: a description of a clinical case

Background. Common variable immune deficiency (CVID) is a complicating comorbid background of COVID-19. Post-infectious immunity formation to SARS-CoV-2 during a pandemic is of particular relevance for such patients. Aim of the study - to present the features of the development of postinfectious humoral immune response in a patient with CVID. Material and methods. Patient K., 49 years old, the diagnosis of CVID verified at the age of 33, has been receiving regular replacement therapy with intravenous immunoglobulins for the last 10 years. After intrafamily contact and infection with SARS-CoV-2 due to the progressive deterioration of the clinical course of COVID-19, he was admitted to a monoinfection hospital. Results. During the treatment of the severe clinical case of COVID-19 a patient with CVID proved to be effective therapy combining anti-cytokine drugs and additional courses of replacement therapy with intravenous immunoglobulins. 6 weeks later from the development of the clinic, the patient was detected specific antibodies to SARS-CoV-2 antigens - IgM (CP 4.73) and IgG (43 BAU), in 4 months the corresponding parameters were 3.55 (CP IgM) and 487 BAU (CP IgG). Comparative analysis of immunophenotyping of the patient's B lymphocytes before the disease, during periods of early and late convalescence showed the dynamics of changes in the number of naive B-lymphocytes, unswitched and switched B-memory cells, plasmablasts, B-reg and B-lymphocytes expressing intercellular cooperation molecules. Conclusion. In the patient with CVID the development of a specific humoral immune response to SARS-CoV-2 after a COVID-19 infection is accompanied by an increase in the proportion of B-memory cells, increased maturation of B-lymphocytes, coordinated dynamics of B-cell suppression and activation parameters. Copyright © 2022 Authors. All rights reserved.

MECHANISMS OF FORMATION OF HYBRID IMMUNITY IN PEOPLE WHO RECOVERED FROM COVID-19 AND WERE VACCINATED WITH SARS-CoV-2 PEPTIDE ANTIGENS

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.

Dynamics of immune status parameters in patients with COVID-19, receiving therapy with inclusion of an IL-6 receptor antagonist

Introduction. Timely prescribing of proactive cytokine storm therapy in patients with COVID-19 using targeted therapy is an important component of success in the treatment of this disease. However, the blockade of receptors to proinflammatory cytokines, in particular to IL-6, leads to shifts in immunoregulatory processes, the nature of which can determine the effectiveness of the therapy and the course of the postCOVID period of rehabilitation of the patient. The aim of the study - to study the dynamics of the parameters of innate and adaptive immunity in a patient with COVID-19 using an IL-6 receptor anatagonist. Material and methods. 30 hospitalized patients were examined with the diagnosis: COVID-19 coronavirus infection (confirmed), moderate form;complication: bilateral polysegmental pneumonia. The comparison group consisted of practically healthy donors (30 people). The dynamics of laboratory parameters (general clinical, biochemical and immunological) were evaluated against the background of therapy with IL-6 blockers. Results. The presence of lymphopenia in the patient, an increase in the level of CRP, LTK, fibrinogen, lactate, IL-6 require the use of proactive anti-cytokine therapy. The timely administration of these drugs (in particular, the IL-6 receptor inhibitor) has a positive effect on the course of the disease and the recovery of patients. In the immune system, after the introduction of monoclonal antibodies to IL-6 receptors, 2 weeks after administration, there is an increase in the maturation of T-lymphocytes, documented by an increase in the content of T-lymphocytes with helper function with a simultaneous decrease in the number of natural killers, B-lymphocytes and disimmunoglobulinemia of IgA, IgM and IgG classes. Conclusion. The use of monoclonal antibodies to IL-6 receptors in patients with a moderate form of COVID-19 leads to dysregulatory processes in the immune system with their gradual normalization by 2 weeks after administration.

POST-VACCINATION IMMUNITY PHENOTYPES UPON USAGE OF EpiVacCorona VACCINE IN THE PERSONS WHO SUFFERED COVID-19

The dominance of reliably immunized population is a fundamental factor in prevention of COVID-19 pandemia, with immune prophylaxis taking a dominant position. Due to lack of clear data on the intensity of specific immunity after a new coronavirus infection, consolidation of immunological memory by vaccination becomes the urgent task, in order to exclude the risk of re-involvement of previously ill patients into the epidemic process. Meanwhile, many questions related to vaccination of COVID-19 survivors do not get distinct answers. To study the features of immune response, using a vaccine based on SARS-CoV-2 peptide antigens (EpiVacCorona), we monitored 81 participants. The inclusion criteria were data confirming COVID-19 in the anamnesis (medical documentation), low levels or absence of antibodies to the SARS-CoV-2 nucleocapsid protein, and negative PCR tests for SARS-CoV-2. When assessing the data of post-vaccinal immunity checked 21 days after 1st dose of the vaccine, the patients were divided into 2 groups: those who did not respond, and those who developed the immune response. In order to identify possible reasons for different phenotypic patterns of humoral response to vaccination, a comparative analysis of B lymphocyte indexes was carried out in these groups. Absolute counts, subpopulation composition and activation potential of peripheral blood B lymphocytes were determined by flow cytofluorometry using appropriate labeled monoclonal antibodies purchased from Beсkman Coulter. Comparative analysis of B lymphocyte indexes on the day of first vaccination showed that the persons who did not respond to the vaccine had smaller counts of circulating B cells, i.e., both percentage and absolute cell numbers, than in comparison group, as well as changed ratio of B1-to-B2 subpopulations. After administration of the first vaccine dose (by day +21), in alternative variant of the antibody response to V1, the differences in the parameters of B cells were presented as a smaller percentage and absolute numbers of regulatory B lymphocytes in non-responding participants. Moreover, the contents of minor B cell subpopulations were decreased in the non-responding group than in the comparison group, thus affecting the values of the B1:B2 ratio. In general, the presented data demonstrate that the absence of secondary immune response to antigens of the SARS-CoV-2 peptide vaccine could be is associated with altered differentiation of B1 and B2 subpopulations, B regulatory lymphocytes, B memory cells.

Dynamics of specific humoral response in COVID-19 patients

Introduction. The pandemic caused by the SARS-CoV-2 virus is an important medical and social problem. It remains unclear the stability of the developed humoral immunity against the SARS-CoV-2 virus, the average duration of preservation of the titer of specific antibodies. The need to identify humoral mechanisms of immune defense in patients with COVID-19 determined the purpose of this study. The aim of the study – to evaluate the dynamics of changes in the content of specific IgG antibodies against various antigens of the SARS-CoV-2 virus and B-lymphocyte subpopulations throughout the year in people who have had COVID-19. Material and methods. The study included 90 patients who had undergone COVID-19 in various forms, subsequently divided into 2 groups: persons with asymptomatic and mild course (57 patients) and with moderate or severe course of the disease (33 patients). The dynamics of the concentration of specific antibodies to the SARS-CoV-2 virus was evaluated by enzyme immunoassay every 3 months for a year. The content of the total pool B-lymphocytes (naive B-lymphocytes, memory B-cells, regulatory B-lymphocytes) and various subpopulations was evaluated by flow cytofluorimetry. Results. When assessing the dynamics of IgG to the S-protein of the SARS-CoV-2 virus, their preservation was noted by the 12th month after recovery. In patients with severe and moderate COVID-19 forms, these indicators are significantly higher. More severe forms of COVID-19 are accompanied by significantly higher content level of memory B cells throughout the observation period. Conclusion. Moderate and severe forms of COVID-19 induce more persistent postinfectious humoral immunity, provided by an increase in memory B cells in comparison with lighter forms.