{"title":"Production of some cytokines as a reflection of various immunoregulatory mechanisms in post-covid myocarditis","authors":"Oxana V. Moskaletc","doi":"10.15789/2220-7619-pos-16582","DOIUrl":"https://doi.org/10.15789/2220-7619-pos-16582","url":null,"abstract":"Currently, the problem of persistent myocardial damage in patients who have had COVID-19 has become one of the most pressing in the practice of cardiologists. The main mechanisms of the pathogenesis of post-COVID myocarditis are associated with a violation of immunoregulation caused by long-term persistence of the virus in the heart muscle and the launch of autoimmune processes that can lead to myocardial remodeling, the formation of myocardiosclerosis and the development of heart failure or arrhythmia. The purpose of this study was to assess the dynamics of the production of certain cytokines (IFNg, IL-4, IL-17А), which may indirectly reflect the activation of various immune response pathways in patients with post-COVID myocarditis, depending on the duration of the disease and the degree of heart failure. The study included 32 patients with post-COVID myocarditis, 36 patients with myocardial cardiosclerosis, and 10 apparently healthy individuals. It was found that in all patients with post-COVID myocarditis, the content of IFNg, IL-4, IL-17А in the blood serum was higher than in patients with myocardial cardiosclerosis (p 0.001; p 0.05; p 0.01, respectively) and conditionally healthy individuals (p 0.001; p 0.01; p 0.001, respectively). Compared with the group of patients with no or moderate severity of symptoms of heart failure (functional class 0–II), those with more severe heart failure (functional class III) had a higher level of interferon gamma (p 0.05). When comparing the results obtained with similar indicators in patients with myocardial cardiosclerosis who have the same degree of heart failure, no statistically significant differences were obtained. The maximum content of IFNg in post-COVID myocarditis was observed in the 2nd week of the disease (p 0.001 compared with the control group); then its level gradually decreased and by the end of the 2nd month there were no longer any significant differences. The opposite trend was observed in relation to the content of IL-4 and IL-17А: in the first two weeks, no statistically significant differences were detected with the control group, but then their content increased quite quickly (p 0.001 compared with the control group by the end of the first month of the disease) and continued to remain the same high until the end of the 2nd month. Thus, monitoring the content of IFNg, IL-4, IL-17А in blood serum can to some extent provide an idea of the sequence of development of the immune response in post-COVID myocarditis. An increase in IFNg levels in the early stages of the disease is probably associated with an increase in the manifestations of heart failure. Th17-mediated mechanisms may be involved in the process of myocardial remodeling resulting in myocardial cardiosclerosis.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. A. Shkuratova, A. E. Khlyntseva, O. V. Kalmantaeva, N. N. Kartsev, A. L. Muzurov, V. V. Firstova
{"title":"Humoral immune response to shiga toxin 2 (Stx2) in children with escherichiosis with hemolytic-uremic syndrome","authors":"M. A. Shkuratova, A. E. Khlyntseva, O. V. Kalmantaeva, N. N. Kartsev, A. L. Muzurov, V. V. Firstova","doi":"10.15789/2220-7619-hir-16859","DOIUrl":"https://doi.org/10.15789/2220-7619-hir-16859","url":null,"abstract":"Shiga toxin-producing Escherichia coli (STEC) causes acute intestinal infections and also causes acute renal failure, especially in children. Shiga toxins (Stx) occupy a central place in the pathogenesis of hemolytic uremic syndrome (HUS) in Escherichiosis. The presented work analyzes the effectiveness of laboratory diagnostics of enterohemorrhagic escherichiosis in patients at the stage of manifestation of HUS and/or acute renal failure using microbiological, immunological research methods and PCR analysis. The study used clinical material from 30 patients in the pediatric intensive care unit of the St. Vladimir Children’s City Clinical Hospital in Moscow with symptoms of HUS aged from 8 months to 5 years. Blood sera from 20 healthy donors were used as control. As a result of PCR analysis, stx2 DNA was detected in 23.3% of cases. Bacteriological research made it possible to sow a pure culture of Escherichia coli O157:H7 in only 3.3% of cases. Since the development of HUS begins in patients with acute intestinal infection caused by Shiga toxin-producing microorganisms starting from the 5th day of the disease, when antibiotic therapy is already carried out, the bacteria can be completely destroyed, which makes it difficult to identify them by bacteriological methods, as well as to detect genes encoding Shiga toxin in PCR analysis. Typically, patients with HUS are admitted to the intensive care unit 5–7 days after the onset of the disease, when class G immunoglobulins specific to the pathogen are already beginning to circulate in the blood. In this regard, the use of immunological tests can be effective to confirm the diagnosis of STEC infection. In our studies, enzyme immunoassay allowed us to detect antibodies to Stx2A in 63.3% and to Stx2B in 43.3% of patients. Using immunoblotting, antibodies to Stx2A were detected in all sera obtained from patients and in 66.7% of cases to Stx2B. Immunoblot analysis was characterized by higher sensitivity for detecting antibodies to Stx2, however, due to the presence of an immunological layer among healthy people, it is preferable to use ELISA analysis. In healthy donors with antibodies to Stx2, the antibody titer was significantly lower than in patients. Laboratory confirmation of the diagnosis of STEC infection is difficult when conducting microbiological and molecular genetic studies, which is confirmed in this work. The effectiveness of laboratory diagnostics can be expanded by performing an ELISA aimed at detecting antibodies to Stx2A.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"22 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Korotaeva, E. Samoilova, D. A. Chepurnova, N. V. Pogosova, D. T. Kuchiev, F. N. Paleev
{"title":"IL-6 and IL-18 cytokine traps in COVID-19","authors":"A. Korotaeva, E. Samoilova, D. A. Chepurnova, N. V. Pogosova, D. T. Kuchiev, F. N. Paleev","doi":"10.15789/2220-7619-iai-16651","DOIUrl":"https://doi.org/10.15789/2220-7619-iai-16651","url":null,"abstract":"Cytokines are mediators of immunity that regulate inflammation. Intensity of inflammatory process is strongly dependent on the cytokine type and duration of its effect. Interleukin 6 (IL-6) and interleukin 18 (IL-18) play an important role in the initiation and progression of inflammation. Cytokines regulate the inflammatory process in different ways by inducing or inhibiting inflammatory reactions. Functional activity of cytokines is limited by trap molecules whose levels determine initiation of protective or pathological effects of interleukins. Soluble glycoprotein sgp130 functions as a trap for IL-6, while IL-18 is controlled by IL-18 binding protein (IL-18BP). High IL-6 and IL-18 levels were recorded in COVID-19 patients, being associated with unfavorable outcome of the disease. Our objective was to compare sgp130 and IL-18BP levels in patients with different degrees of COVID-19. Retrospective study included 74 COVID-19 patients (40 men and 34 women) aged 63±14 years. The patients were assigned to groups according to severity of lung damage. Group 1 included patients without lung damage; group 2, patients with moderate pneumonia ( 50% lung damage); group 3, patients with severe pneumonia ( 50% lung damage). Plasma levels of cytokines and their trap molecules were determined by quantitative immunoenzyme assay. IL-6 and IL-18 plasma concentrations increased with COVID-19 severity. Ambiguous changes were recorded for their traps. Plasma levels of sgp130 were lower in patients with moderate pneumonia than in patients without lung damage. In patients with severe pneumonia sgp130 plasma concentrations were higher than those in patients with mild pneumonia, being similar to those in patients without lung damage. In contrast to sgp130, IL-18BP levels decreased with COVID-19 severity. Thus, an increase in IL-6 and IL-18 levels parallel to COVID-19 severity is accompanied by ambiguous changes in the levels of their trap molecules. The ratio between the levels of IL-6 and IL-18 and their traps reflects the degree of COVID-19 severity.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"2 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna D. Sheynova, O. A. Podosokorskaya, E. O. Gubernatorova
{"title":"The effect of the probiotic bacteria Akkermansia Muciniphila in intestinal homeostasis and dss-induced inflammation in mice","authors":"Anna D. Sheynova, O. A. Podosokorskaya, E. O. Gubernatorova","doi":"10.15789/2220-7619-teo-16882","DOIUrl":"https://doi.org/10.15789/2220-7619-teo-16882","url":null,"abstract":"Akkermansia muciniphila is a Gram-negative anaerobic bacterium, a component of the normal human intestinal microbiota. A decrease in the presence of this bacterium is associated with pathologies, including metabolic disorders, intestinal inflammation and colorectal cancer. A. muciniphila is a probiotic approved for patients with diabetes and obesity. In recent years, A. muciniphila was studied in the control of intestinal inflammation and colorectal cancer. The exact mechanisms of A. muciniphila action remain unclear, while the use of different administration protocols shows different effects in mouse models of colitis and colorectal cancer. We reported that A. muciniphila has distinct effects on intestinal mucin production depending on viable or pasteurized form of bacteria. Another factor affecting the outcome of the A. muciniphila administration is the number of bacteria. To address how the dose of bacteria may affect the severity of acute intestinal inflammation wild-type mice were subjected to daily oral injections with 10⁸ CFU or 109 CFU of viable A. muciniphila for two weeks; the control group was injected with PBS. After that, groups were subjected to the induction of acute colitis by adding 7% DSS to drinking water for five days. 8 days after the onset of colitis induction, a morphometric assessment of the colitis severity was performed. Mice given a high dose of A. muciniphila (109 CFU) were found to be protected from developing severe colitis. RT-PCR analysis of colon samples from mice receiving a high dose of bacteria showed an increase in the gene expression of antimicrobial peptides, IL-17A, IL-17F. Interestingly, the protective effect of A. muciniphila was observed only in a high dose group, but not in a low dose group. Our data suggest that A. muciniphila provides the protective effect in colitis and highlight the importance of selecting the dose of the bacterium for proper interpretation.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative assessment of interferon activity in influenza and COVID-19","authors":"T. Ospelnikova, O. A. Svitich, F. I. Ershov","doi":"10.15789/2220-7619-cao-16821","DOIUrl":"https://doi.org/10.15789/2220-7619-cao-16821","url":null,"abstract":"Among respiratory viruses, the most serious complications are caused by influenza A and B viruses, as well as coronaviruses. Most studies determined the absolute content of interferons (IFNs) of different types in blood serum. However, serum IFN protein concentrations do not always reflect the level of antiviral protection. The purpose of this study was a comparative assessment of interferon status in patients with ARVI: influenza and the acute stage of COVID-19. Materials and methods. We used biomaterial in the form of whole blood samples from 113 patients with influenza and 110 patients in the acute phase of moderate COVID-19. The body’s antiviral defense during ARVI was assessed by determining the activity of type I and II interferons produced by blood leukocytes using the “Interferon status” method in a cell-virus system simulated in vitro. Results. This work reveals a statistically significant decrease in the biological activity of interferons produced by blood leukocytes in influenza and a deficiency of IFN activity in COVID-19, compared with reference values, and also shows possible prospects for the treatment of these nosologies with such immunoactive drugs as IFN inducers (cycloferon, Kagocel) and immunomodulators (ingavirin, multicomponent vaccine Immunovac-VP-4). Conclusion. The results of IFN activity are necessary to assess the antiviral potential of the body, especially with COVID-19, given the “novelty” of the infection, the severity and variety of its clinical manifestations. Today it is known that the SARS-CoV-2 virus is capable of penetrating not only into the epithelial cells of the upper respiratory tract, epithelial cells of the stomach and intestines, but also into the cells of the esophagus, heart, adrenal glands, bladder, brain, as well as into the vascular endothelium and macrophages. Coronavirus SARS-CoV-2 inhibits the expression of cellular genes, including innate immune genes, and has a negative effect on the IFN system. The use of IFN inducers and immunomodulators for influenza and COVID-19 has shown immunological feasibility and clinical promise.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Byazrova, M. Sukhova, A. Mikhailov, A. F. Romanova, G. M. Yusubaliyeva, A. Filatov
{"title":"Plasmablast response during acute SARS-CoV-2 infection","authors":"M. Byazrova, M. Sukhova, A. Mikhailov, A. F. Romanova, G. M. Yusubaliyeva, A. Filatov","doi":"10.15789/2220-7619-prd-16670","DOIUrl":"https://doi.org/10.15789/2220-7619-prd-16670","url":null,"abstract":"Plasmablasts are a population of short-lived B cells that appear in the circulation shortly after vaccination and during acute infection. Plasmablasts are formed from resting B lymphocytes, from which they differ in their ability to secrete antibodies, making them similar to plasma cells. Plasmablasts are terminally differentiated cells that can form at various nodes and branches of the B cell response. The plasmablast response is an indicator of the success of vaccination and also helps in predicting antibody levels after recovery or vaccination. However, the definition and classification of plasmablasts faces great experimental and theoretical difficulties. The aim of the work was to determine the characteristics of the plasmablast response during acute SARS-CoV-2 infection. The study included patients (n = 28) with a severe form of COVID-19. Blood sampling was carried out once on the 10–18th day from the moment of hospitalization. B cells were isolated by immunomagnetic separation. Cells were phenotyped using flow cytometry. Secretion of IgM and IgG was determined by ELISpot method. B cell subsets were isolated using a cell sorter. Patients with COVID-19 had an approximately fourfold increase in total plasmablast levels compared to healthy donors. An even more pronounced excess over the negative control was observed for RBD-specific plasmablasts. In terms of their composition, plasmablasts were one third IgM⁺ cells. This distribution between B-cell BCR receptor isotypes was consistent with the primary nature of the immune response in COVID-19. Approximately a third of plasmablasts carried the CD138 antigen. CD138 marker is characteristic of the late stage of plasmablast maturation and is also found on plasma cells. The CD27+CD38⁺ population was divided according to the expression of the CD138 antigen. Using the ELISpot method, we have shown that a significant portion of circulating plasmablasts are antibody-secreting cells. Among circulating plasmablasts, both early and late plasmablasts can be distinguished, which are characterized by the absence of a surface BCR, but which carry the CD138 antigen. Determining how plasmablasts relate to other B cell populations is of paramount importance for the development of new treatments for COVID-19 and for the creation of promising vaccines against SARS-CoV-2 infection.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"11 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The avidity of virus-specific antibodies obtained from in vitro stimulated memory b cells does not change one month after booster with Sputnik V or Comirnaty","authors":"E. Astakhova","doi":"10.15789/2220-7619-tao-16938","DOIUrl":"https://doi.org/10.15789/2220-7619-tao-16938","url":null,"abstract":"The protective properties of long-term immunological memory after vaccination against COVID-19 are characterized by the neutralizing activity of serum antibodies and antibodies secreted by memory B cells upon repeated encounter with the antigen. Somatic hypermutations occurring in the immunoglobulin genes of memory B cells are one of the mechanisms for increasing the affinity of antibodies. At the moment, the effect of booster vaccination against COVID-19 with vector vaccines, on the maturation of memory B cells remains poorly understood. The purpose of this work was to determine how COVID-19 booster affects the affinity of RBD-specific IgG antibodies secreted by memory B cells. B lymphocytes were isolated from peripheral mononuclear blood cells of volunteers who had been revaccinated against COVID-19 with Sputnik V or Comirnaty. B cells were stimulated in vitro with CD40L expressed on the surface of A549 feeder cells and IL-21. Supernatants were concentrated 8-fold using centrifugal concentrators. In the obtained supernatants from stimulated memory B cells, the level of IgG antibodies specific to wild-type RBD was determined by enzyme-linked immunosorbent assay (ELISA). To determine the avidity index, ELISA with 7M urea was provided. It was shown that despite a general increase in the amount of antigen-specific IgG antibodies obtained from stimulated memory B cells, there was no change in the avidity of these antibodies one month after booster in both groups of donors. The obtained results contribute to the understanding of the mechanisms of memory B cell maturation after booster vaccinations against COVID-19 and may be useful for deciding on the strategy of booster vaccination.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"18 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Maslennikova, I. V. Nekrasova, Erjavec M. Starčič, M. Kuznetsova
{"title":"The influence of neutrophils and their exoproducts on biofilm biomass, bacterial viability and conjugative transfer into Escherichia Coli","authors":"I. Maslennikova, I. V. Nekrasova, Erjavec M. Starčič, M. Kuznetsova","doi":"10.15789/2220-7619-tio-16691","DOIUrl":"https://doi.org/10.15789/2220-7619-tio-16691","url":null,"abstract":"The purpose of this study was to investigate the effect of neutrophils and their antimicrobial factors, hydrogen peroxide and defensin α, on the biofilm biomass, the viability of bacteria in the biofilm and the efficiency of conjugative transfer of the pOX38:Cm plasmid from the E. coli N4i pOX38:Cm strain into different E. coli strains (commensal К12 TG1 and uropathogenic DL82, R32 and R45). The biofilm of the recipient E. coli TG1 with the donor E. coli N4i pOX38:Cm increased when 10⁵ cells/ml of neutrophils were added compared to the control, while the biofilm biomass of the uropathogenic E. coli recipient strains DL82/E. coli R45 with the donor E. coli N4i pOX38:Cm decreased when 10⁶/10⁴–10⁶ cells/ml of neutrophils were added, respectively. The survival of recipient E. coli TG1 cells and transconjugants in the biofilm was, compared to the control, higher when 10⁴, 10⁵, 10⁶ cells/ml of neutrophils were added. The addition of 0.1 mM H₂O₂ increased biofilm formation of E. coli DL82 and E. coli R45, and addition of 0.5 mM H₂O₂ reduced biofilm formation of E. coli DL82, while 0.5 mM or 2.5 mM reduced the E. coli R45 bacterial biofilm biomass in the conjugative mixture. The frequency of the pOX38:Cm conjugative transfer was lower in the presence of 2.5 mM H₂O₂ in the N4i pOX38:Cm × DL82 biofilm, and also in the presence of 0.5 and 2.5 mM H₂O₂ in the N4i pOX38:Cm × R45 biofilm, compared to the control. The frequency of pOX38:Cm conjugation from the donor E. coli N4i pOX38:Cm into E. coli DL82 decreased, when 5 or 25 ng/ml defensin α were added and the conjugation frequency in the mating mixture N4i pOX38:Cm×R45 decreased, when 5 ng/ml were added, while, when 25 ng/ml of defensin α were added it increased.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Blyakher, I. Fedorova, S. I. Koteleva, I. Kapustin, E. Tulskaya, Z. K. Ramazanova, E. E. Odintsov, S. V. Sandalova, L. Novikova, S. Bochkareva
{"title":"Algorithm for assessing the level of T cell immune response against SARS-CoV-2 and the results of its application in unvaccinated and vaccinated people who have been infected with COVID-19","authors":"M. Blyakher, I. Fedorova, S. I. Koteleva, I. Kapustin, E. Tulskaya, Z. K. Ramazanova, E. E. Odintsov, S. V. Sandalova, L. Novikova, S. Bochkareva","doi":"10.15789/2220-7619-afa-16736","DOIUrl":"https://doi.org/10.15789/2220-7619-afa-16736","url":null,"abstract":"Antigen (AG)-specific T cell activity was compared in two groups of patients: those who underwent COVID-19 in 2021 during the circulation of the SARS-CoV-2 delta virus strain (43 individuals); and those who underwent COVID-19 in 2022 (Omicron strain, 23 individuals). The diagnosis was confirmed by PCR analysis of nasopharyngeal and oropharyngeal swabs. The 23 individuals following COVID-19 caused by SARS-CoV-2 (omicron) were part of a cohort of 41 volunteers who were examined multiple times during 2021–2023: during vaccination, after vaccination, before revaccination, and subsequently after illness (6–8 times in total). Due to this, it was possible to compare the indices of specific humoral and cellular immunity in the same patients 1–2 months before and after breakthrough infection. Detection of AG-specific T cells and assessment of their activity by AG-stimulated IFNγ production was carried out by our own previously developed method (Patent RU № 2780369 C1). For stimulation of memory T effectors in vitro, the same antigens were used to determine the concentration of antibodies against SARS-CoV-2 by ELISA method. A total of about 300 blood samples from healthy subjects and patients after COVID-19 were analyzed. Each sample was tested against 3 SARS-CoV-2 antigens and in 2 stimulation modes. A qualitative assessment algorithm for AG-specific T cell activity has been proposed that can be used to monitor the state of cellular immunity in a population in which SARS-CoV-2 virus continues to circulate and to create insights into what level of T cell activation is sufficient to prevent or reduce the severity of SARS-CoV-2 infection. Unvaccinated COVID-19 (SARS-CoV-2, Delta) survivors lacked AG-specific T cells to RBD SARS-CoV-2, but T cell specificity to full-length S glycoprotein at the same level, qualitatively assessed as low in 52% of the group, persisted for up to six months. In previously unvaccinated COVID-19 vaccinees, this duration of persistence of AG-specific T cells in circulating blood was achieved only after revaccination. Hybrid immunity, which we traced as a result of vaccination after COVID-19 (Delta strain) or as a breakthrough infection (SARS-CoV-2, Omicron), is characterized by the highest indices of memory T cell activity (43–46% of the group — normal activity of AG-specific cells, 30–43% — high activity) to all used antigens and the longest duration of preservation of indices at this level. Further investigation of the level of antiviral immunity after COVID-19 may be important for predicting the outcome of new waves of SARS-CoV-2 infection.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"3 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivan M. Rashchupkin, I. Meledina, M. Kotova, O. Zheltova
{"title":"PD-1 AND Tim-3 Expression on different subpopulations of monocytes in chronic often recurrent herpesvirus infection","authors":"Ivan M. Rashchupkin, I. Meledina, M. Kotova, O. Zheltova","doi":"10.15789/2220-7619-pat-16807","DOIUrl":"https://doi.org/10.15789/2220-7619-pat-16807","url":null,"abstract":"More than half of the world’s population is infected with the herpes simplex virus. In most cases, infection is not accompanied by symptoms, but in some people the disease occurs as a chronic infection with frequent and severe relapses. One of the most likely reasons for this may be a dysregulation of the immune system. In recent years, the role of checkpoint molecules, in particular PD-1 and Tim-3, in the regulation of the immune response and the functions of immunocompetent cells has been actively studied. Activation of PD-1 and Tim-3 on T cells has previously been shown to suppress the immune response. PD-1 and Tim-3 are also expressed on other immune cells, in particular monocytes. However, the expression of these molecules on monocytes during chronic viral infections has not been previously studied. The study was aimed at assessing the level of PD-1 and Tim-3 expression on various populations of monocytes in patients with chronic often recurrent herpesvirus infection. Twenty-six patients were recruited into the study. All patients received antiviral and immunomodulatory therapy in the immunological department. The number of classical, intermediate, and non-classical monocytes and the expression of PD-1 and Tim-3 on monocytes, were assessed by flow cytometry before and after the therapy. Monocytes were isolated from peripheral blood, and subpopulations were divided according to the level of expression of CD14 and CD16. In patients with herpes, a reduced number of monocytes was observed in comparison with healthy donors. The relative number of PD-1-positive monocytes, the mean fluorescence intensity of PD-1 and Tim-3, and the number of double-positive cells were reduced in herpes patients in all three monocyte subpopulations examined. Three months after therapy, the response to the therapy was assessed; patients who did not have a single recurrence of herpes within 3 months were considered to respond. Responding patients had a lower initial content of double-positive cells among intermediate and non-classical monocytes. The decrease in the level of PD-1 and Tim-3 positive monocytes during herpesvirus infection revealed in the present study may indicate the involvement of monocytes deficient in the expression of checkpoint molecules in the pathogenesis of the disease.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}