ABSTRACT
Employees of medical organizations are one of the risk groups for infection with a new coronavirus infection (COVID-19), including with the development of severe clinical forms. The aim of the study was to analyze the clinical manifestations of a new coronavirus infection in medical workers with the determination of laboratory markers for the development of severe COVID-19. Material and methods. The study included 186 medical workers who had COVID-19 in 2020. In 67 people (observation group), the disease occurred in the form of pneumonia, in 119 people (comparison group) - acute respiratory infection caused by SARS-CoV-2. In the acute period of the disease, a laboratory examination was carried out: a general clinical blood test, CD-typing of lymphocyte subpopulations, assessment of biochemical parameters, determination of parameters of the hemostasis system and cytokine levels. Using the binary logistic regression method, we have built multifactor models. To determine the threshold values of the indicators, we used ROC analysis. Statistical processing of materials was carried out using Microsoft Office 2016 and IBM SPSS Statistics (version 26). The differences were considered statistically significant at p<0.05. Results and discussion. The most frequent clinical manifestations of COVID-19 were: weakness, fever, myalgia, arthralgia, difficulty in nasal breathing, serous-mucous discharge from the nose, sore throat, cough, feeling of "tightness" in the chest, shortness of breath, headache, pain in the eyeballs, dizziness, anosmia, ageusia and dyspeptic manifestations in the form of diarrhea, nausea or vomiting. Markers associated with the development of severe pneumonia associated with COVID-19 have been identified. Threshold values of laboratory parameters for predicting the severe course of COVID-19 were determined: the number of platelets (less than 239x109/l), lymphocytes (less than 1.955x109/l), cytotoxic T-lymphocytes (less than 0.455x109/l), T-helper cells (less than 0.855x109/l), NK-cells (less than 0.205x109/l), ESR (more than 11.5 mm/h), LDH (more than 196 units/l), total protein (less than 71.55 g/l), D-dimer (more than 0.325 mcg/ml), CRP (more than 4.17 mg/l), IL-6 (more than 3.63 pg/l). Conclusion. The data obtained make it possible to predict the possibility of developing a severe variant of the COVID-19 course.Copyright © 2022 Infectious Diseases: News, Opinions, Training. All rights reserved.
ABSTRACT
Vaccines based on recombinant mRNA technology helped to control the pandemic caused by the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). Clinical trials for showed that these vaccines are safe and effective and promote a strong type 1 driven T cell response. Yet, several reports claimed that SARS-CoV-2 mRNA vaccination might favor the onset, worsening or the reactivation of autoimmune disorders like pemphigus and bullous pemphigoid. However, no study demonstrated a direct immunological link between mRNA vaccination and disease appearance/worsening. We aimed to analyze the immunological and clinical effects exerted by mRNA booster vaccinations for SARS-CoV-2 in a cohort of patients with pemphigus (n=9), bullous pemphigoid (n=4) and in healthy individuals (n=5). Patients and healthy individuals were monitored at baseline, and after two and four weeks of mRNA vaccination. We assessed the clinical disease status, antibodies against the SARS-CoV-2 spike protein, antibody levels for BP180/230, DSG1/3 and tetanustoxoid. We also determined the distribution of peripheral T helper / T follicular cell subsets, intracellular cytokine production of T cells and cytokine serum levels. Our results show that booster vaccination increased anti spike protein IgG, while tetanustoxoid igC and skin-specific autoantibody titers were not or minimally affected. We observed an increase in Th1/Th17.1 cells, together with an increase in the intracellular production of IFN-gamma, IL-4 and IL-21 in peripheral T cells of pemphigus patients. Importantly, clinical activity in both remittent patients and in patients with active disease remained stable. In summary, vaccination with mRNA vaccines induced a specific activation of the humoral system with production of protective antibodies against the Sars-CoV-2 spike protein without affecting autoimmune disease activity in patients with pemphigus and bullous pemphigoid.Copyright © 2023
ABSTRACT
Organ transplant recipients show weaker immune responses to vaccines than immunocompetent individuals, which may be related to the repertoire of HLAbound vaccine antigens presented to T lymphocytes. The HLA evolutionary divergence (HED) metric, which quantifies pairwise allele divergence at each HLA locus, provides a primary measure of the breadth of the immunopeptidome. We recently showed that high class I HED of the donor is a strong and independent driver of allograft rejection in a large cohort of liver transplant recipients. Here, in the same cohort, we explored the relation between HED, the size of the predicted immunopeptidome derived from vaccine antigens, and the quality of vaccine responses. We analyzed humoral response to the SARS-CoV-2 BNT162b2 vaccine (n = 310 patients;undetectable anti-spike IgG titers considered as no response, <=250 BAU/mL as moderate and >250 BAU/mL as strong response) and Hepatitis B virus (HBV) vaccine (n = 424 patients;anti-HBs IgG <10 mIU/mL considered as no response, 10-100 mIU/mL as moderate and >=100 mIU/mL as strong response). HED at HLA-A, -B, -C, -DRB1, -DQA1 and -DQB1 loci were measured using the Grantham distance. NetMHCIIpan-4.0 was used to predict the binding to HLA-DQ molecules of all possible 15mer peptides derived from the Spike and HBS sequences. For each vaccine, HED at the DQB1 locus, but not at the other loci, was significantly higher in responders than in non-responders (p = 0.0003), independent of response-associated covariates (age, time since transplant, immunosuppression). Moreover, for both vaccines, there was a strong relationship between DQB1 HED, the diversity of the immunopeptidome and the quality of the vaccine response. In conclusion, DQB1 HED is a critical determinant of humoral response to vaccines in liver transplant recipients. This metric could guide the design of future vaccines as it predicts the magnitude of the repertoire of vaccine-derived peptides presented to CD4 helper T cells.
ABSTRACT
Current review presents a brief overview of the immune system dysregulation during acute COVID-19 and illustrates the main alterations in peripheral blood CD4+ T-cell (Th) subsets as well as related target cells. Effects of dendritic cell dysfunction induced by SARS-CoV-2 exhibited decreased expression of cell-surface HLA-DR, CCR7 as well as co-stimulatory molecules CD80 and CD86, suggesting reduced antigen presentation, migratory and activation capacities of peripheral blood dendritic cells. SARS-CoV-2-specific Th cells could be detected as early as days 2-4 post-symptom onset, whereas the prolonged lack of SARS-CoV-2-specific Th cells was associated with severe and/or poor COVID-19 outcome. Firstly, in acute COVID-19 the frequency of Th1 cell was comparable with control levels, but several studies have reported about upregulated inhibitory immune checkpoint receptors and exhaustion-associated molecules (TIM3, PD-1, BTLA, TIGIT etc.) on circulating CD8+ T-cells and NK-cells, whereas the macrophage count was increased in bronchoalveolar lavage (BAL) samples. Next, type 2 immune responses are mediated mainly by Th2 cells, and several studies have revealed a skewing towards dominance of Th2 cell subset in peripheral blood samples from patients with acute COVID-19. Furthermore, the decrease of circulating main Th2 target cells - basophiles and eosinophils - were associated with severe COVID-19, whereas the lung tissue was enriched with mast cells and relevant mediators released during degranulation. Moreover, the frequency of peripheral blood Th17 cells was closely linked to COVID-19 severity, so that low level of Th17 cells was observed in patients with severe COVID-19, but in BAL the relative number of Th17 cells as well as the concentrations of relevant effector cytokines were dramatically increased. It was shown that severe COVID-19 patients vs. healthy control had higher relative numbers of neutrophils if compared, and the majority of patients with COVID-19 had increased frequency and absolute number of immature neutrophils with altered ROS production. Finally, the frequency of Tfh cells was decreased during acute COVID-19 infection. Elevated count of activated Tfh were found as well as the alterations in Tfh cell subsets characterized by decreased "regulatory" Tfh1 cell and increased "pro-inflammatory" Tfh2 as well as Tfh17 cell subsets were revealed. Descriptions of peripheral blood B cells during an acute SARS-CoV-2 infection werev reported as relative B cell lymphopenia with decreased frequency of "naive" and memory B cell subsets, as well as increased level of CD27hiCD38hiCD24- plasma cell precursors and atypical CD21low B cells. Thus, the emerging evidence suggests that functional alterations occur in all Th cell subsets being linked with loss-of-functions of main Th cell subsets target cells. Furthermore, recovered individuals could suffer from long-term immune dysregulation and other persistent symptoms lasting for many months even after SARS-CoV-2 elimination, a condition referred to as post-acute COVID-19 syndrome.Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
Introduction: Persistence of SARS-Cov-2 leads to immunosuppression and lack of viral control. Better understanding of the immune response throughout the course of evolution is important for a better patient management. Method(s): Prospective observational longitudinal study of 91 hospitalised patients with different degrees of severity (moderate, severe, critical). In 72 we obtained >=2 blood samples and classified them into viral phase (1-9 days after clinical onset), early inflammatory (10-16), and late inflammatory (>17). We included clinical data, immune cell counts, proinflammatory cytokine levels, serum inflammatory markers, and tissue damage. Result(s): We observed higher serum IL-6 levels in the more severe groups, from the first sample. In inflammatory phases, we found a significant decrease in IL-6 and LDH in moderate, severe and survivors, and high persistence in critical and deceased patients. The biphasic behavior of IL-6 described, first neutrophil recruitment, epithelial and endothelial damage and then, after achieving viral control, CD4 differentiation, Th cells response and potentiation of Ac response, could explain these differences between those who do not achieve viral control (critical, deceased) and those who do. Conclusion(s): - IL-6 levels at 10-16 days may indicate whether or not viral control is achieved and whether there may be progression to critical stage/death.
ABSTRACT
The proceedings contain 14 papers. The topics discussed include: MOG-positive anti-NMDA receptor encephalitis with no demyelinating lesions: two case reports;safety and tolerability of rozanolixizumab in the randomized phase 3 MycarinG study;Outcomes from RAISE: A randomized, phase 3 trial of zilucoplan in generalized myasthenia gravis;efficacy and safety of zilucoplan in myasthenia gravis: responder analysis from the randomized Phase 3 RAISE trial;distinct effects among calcium-binding proteins for microglia to produce chemokines associated with the clinical severity of ALS;astroglial connexin 43 is a novel therapeutic target for a chronic multiple sclerosis model;targeting lymphocytes in SPMS: Th cell populations as a biomarker to predict the efficacy of Siponimod;CSF lysophospholipids as a novel biomarker in relapsing-remitting multiple sclerosis;the immune response to SARS-COV-2 MRNA vaccines in siponimod-treated patients with secondary progressive multiple sclerosis;patient characteristics of siponimod-treated SPMS patients in Japan: interim results from post-marketing surveillance;and efficacy of ravulizumab across sex and age subgroups of patients with generalized myasthenia gravis: a post hoc analysis of the CHAMPION MG study.
ABSTRACT
Current review presents a brief overview of the immune system dysregulation during acute COVID-19 and illustrates the main alterations in peripheral blood CD4+ T-cell (Th) subsets as well as related target cells. Effects of dendritic cell dysfunction induced by SARS-CoV-2 exhibited decreased expression of cell-surface HLA-DR, CCR7 as well as co-stimulatory molecules CD80 and CD86, suggesting reduced antigen presentation, migratory and activation capacities of peripheral blood dendritic cells. SARS-CoV-2-specific Th cells could be detected as early as days 2–4 post-symptom onset, whereas the prolonged lack of SARS-CoV-2-specific Th cells was associated with severe and/or poor COVID-19 outcome. Firstly, in acute COVID-19 the frequency of Th1 cell was comparable with control levels, but several studies have reported about upregulated inhibitory immune checkpoint receptors and exhaustion-associated molecules (TIM3, PD-1, BTLA, TIGIT etc.) on circulating CD8+ T-cells and NK-cells, whereas the macrophage count was increased in bronchoalveolar lavage (BAL) samples. Next, type 2 immune responses are mediated mainly by Th2 cells, and several studies have revealed a skewing towards dominance of Th2 cell subset in peripheral blood samples from patients with acute COVID-19. Furthermore, the decrease of circulating main Th2 target cells — basophiles and eosinophils — were associated with severe COVID-19, whereas the lung tissue was enriched with mast cells and relevant mediators released during degranulation. Moreover, the frequency of peripheral blood Th17 cells was closely linked to COVID-19 severity, so that low level of Th17 cells was observed in patients with severe COVID-19, but in BAL the relative number of Th17 cells as well as the concentrations of relevant effector cytokines were dramatically increased. It was shown that severe COVID-19 patients vs. healthy control had higher relative numbers of neutrophils if compared, and the majority of patients with COVID-19 had increased frequency and absolute number of immature neutrophils with altered ROS production. Finally, the frequency of Tfh cells was decreased during acute COVID-19 infection. Elevated count of activated Tfh were found as well as the alterations in Tfh cell subsets characterized by decreased "regulatory” Tfh1 cell and increased "pro-inflammatory” Tfh2 as well as Tfh17 cell subsets were revealed. Descriptions of peripheral blood B cells during an acute SARS-CoV-2 infection werev reported as relative B cell lymphopenia with decreased frequency of "naïve” and memory B cell subsets, as well as increased level of CD27hiCD38hiCD24– plasma cell precursors and atypical CD21low B cells. Thus, the emerging evidence suggests that functional alterations occur in all Th cell subsets being linked with loss-of-functions of main Th cell subsets target cells. Furthermore, recovered individuals could suffer from long-term immune dysregulation and other persistent symptoms lasting for many months even after SARS-CoV-2 elimination, a condition referred to as post-acute COVID-19 syndrome.
ABSTRACT
To date, there is no consensus explaining the relationship between varying concentrations of IFNgamma and the severity of infection caused by SARS-CoV-2. The aim of this article was to analyze and formulate conclusions from the selected studies and publications, which, in sum, provide a potentially reasonable view on the role of IFNgamma in COVID-19 pathogenesis. This article highlights current data on the immunological role of IFNgamma which affects differentiation of naive T helper cells, acting as a polarizing factor. It activates the major histocompatibility complex (MHC) class I and II, by increasing the expression of MHC I/II subunits, inhibiting replication of the viral particles by initiating activation of interferon-stimulated genes followed by subsequent synthesis of antiviral proteins. Moreover, IFNgamma activates the production of cytokines by T cells, enhancing cytotoxic activity of the T killers. IFNgamma exerts immunostimulatory and immunomodulatory effects via STAT1, SOCS1 and PIAS genes, thus regulating activation of the JAK-STAT signaling pathway. A number of studies were considered where the patterns of changes in serum IFNgamma concentration were examined in viral infections and SARS-CoV-2. We performed a systemic analysis of the results of studies that showed a relationship between high concentrations of IFNgamma and COVID-19 severity. In a number of studies, the significantly high levels of IFNgamma in COVID-19 patients were often associated with a poor outcome of the disease. The median values of the IFNgamma concentration in severe COVID-19 were found to be significantly higher compared to the results obtained in the cases of moderate severity. It shows an increase, in parallel with viral load in the nasopharyngeal samples upon worsening of the clinical condition. Based on the data on the decreased IFNgamma concentrations in convalescent patients, the mechanism of antagonism between IFNgamma and IL-4 is considered, where the decreases serum concentrations of IFNgamma along with increasing level of IL-4 may be an indirect proof of normal adaptive immune response with subsequent development of antibodies to SARS-CoV-2 and gradual elimination of the virus from the body. Moreover, the evidence is discussed that the patients harboring some parasitic infections (Toxoplasma gondii, Cryptosporidium, Blastocystis hominis, Giardia duodenalis, Entamoeba histolytica) with persistently elevated level of IFNgamma are at reduced risk for severe course of COVID-19. Copyright © 2022, SPb RAACI.
ABSTRACT
Currently, as the SARS-CoV-2 pandemic evolves, there has been increasingly more attention paid to building natural and vaccine-induced immunity against SARS-CoV-2 and related disease known as COVID-19. Widespread preventive vaccination plays an important role in effectively protecting people from viral infections and can reduce national economic costs. Purpose - to study peripheral blood cell subset composition and magnitude of humoral response in vaccinated Gam-COVID-Vac subjects. The prospective study included 352 patients, of which 194 (119 women and 75 men) underwent an immunogram study and assessed level of anti-SARS-CoV-2 antibodies. In patients, the study of the lymphocyte subset composition and estimation of anti-SARS-CoV-2 antibodies was carried out at two time points - prior to vaccination and 90 days after inoculated component 1 of the Gam-COVID-Vac vaccine. In general, vaccination was well tolerated by patients, with no serious adverse events after immunization. The reaction to the vaccine (fever, malaise, headache, local reactions) was short-term (1-2 days) and more often noted after inoculated vaccine component 2. Comparatively analyzed immunogram parameters in females before and after vaccination revealed increased relative level of T-lymphocytes (CD3+), T-helper cell subset (CD3+CD4+), increased absolute and relative level of activated CD3+CD25+ T-lymphocytes, but decreased absolute and relative level of natural killer (CD3-CD56+CD16+) and natural killer T-cell (CD3+CD56+CD16+) cell subsets as well as decreased CD147 receptor expression on T-lymphocytes. Similar patterns were also found while examining the immunogram in males exepting increased level of lymphocytes and lowered CD147 expression on both T- and B-lymphocytes. No changes in the parameters of the immune T-cell arm was found. The high efficacy of the vaccine was confirmed by development of SARS-CoV-2-specific class G antiviral antibodies in 97.5% and 92.3% of vaccinated females and males, respectively. The data obtained evidence that: 1) vaccination induces a specific humoral immune response determined three months post-vaccination, and 2) it caused no serious disturbances in the immune system functioning, which could be reflected in the peripheral blood lymphocyte subset composition. Thus, the data presented allow to conclude that Gam-COVID-Vac is effective vaccine against SARS-CoV-2 infection. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
Currently, as the SARS-CoV-2 pandemic evolves, there has been increasingly more attention paid to building natural and vaccine-induced immunity against SARS-CoV-2 and related disease known as COVID-19. Widespread preventive vaccination plays an important role in effectively protecting people from viral infections and can reduce national economic costs. Purpose - to study peripheral blood cell subset composition and magnitude of humoral response in vaccinated Gam-COVID-Vac subjects. The prospective study included 352 patients, of which 194 (119 women and 75 men) underwent an immunogram study and assessed level of anti-SARS-CoV-2 antibodies. In patients, the study of the lymphocyte subset composition and estimation of anti-SARS-CoV-2 antibodies was carried out at two time points - prior to vaccination and 90 days after inoculated component 1 of the Gam-COVID-Vac vaccine. In general, vaccination was well tolerated by patients, with no serious adverse events after immunization. The reaction to the vaccine (fever, malaise, headache, local reactions) was short-term (1-2 days) and more often noted after inoculated vaccine component 2. Comparatively analyzed immunogram parameters in females before and after vaccination revealed increased relative level of T-lymphocytes (CD3+), T-helper cell subset (CD3+CD4+), increased absolute and relative level of activated CD3+CD25+ T-lymphocytes, but decreased absolute and relative level of natural killer (CD3-CD56+CD16+) and natural killer T-cell (CD3+CD56+CD16+) cell subsets as well as decreased CD147 receptor expression on T-lymphocytes. Similar patterns were also found while examining the immunogram in males exepting increased level of lymphocytes and lowered CD147 expression on both T- and B-lymphocytes. No changes in the parameters of the immune T-cell arm was found. The high efficacy of the vaccine was confirmed by development of SARS-CoV-2-specific class G antiviral antibodies in 97.5% and 92.3% of vaccinated females and males, respectively. The data obtained evidence that: 1) vaccination induces a specific humoral immune response determined three months post-vaccination, and 2) it caused no serious disturbances in the immune system functioning, which could be reflected in the peripheral blood lymphocyte subset composition. Thus, the data presented allow to conclude that Gam-COVID-Vac is effective vaccine against SARS-CoV-2 infection. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
Background: Disease-modifying therapies (DMTs) in patients with multiple sclerosis (pwMS) are known to impact the cellular immune response to SARS-CoV-2 vaccines. In this study, we aim to elucidate a broader cytokine profile of involved T cells for various DMTs. Method(s): 131 pwMS on different DMTs vaccinated with SARSCoV- 2 mRNA vaccines were recruited for this prospective cohort. Blood was drawn post 2nd and 3rd dose. Using a cartridge based multiplex assay (ELLATM), interleukin (IL)-5, IL-10, IL-2, IL-4, IL-17A, IL-13, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were measured in blood stimulated with SARS-CoV-2 antigens (Ag) to evaluate T cell response. In comparison, SARS-CoV-2 spike antibodies were measured. mRNA vaccine non-responders were administered NVX-CoV2373 protein- based vaccine, and the corresponding immune responses were measured. Result(s): After two mRNA vaccines, IFN-gamma, and IL-2 responses were significant and comparable between patients treated with glatiramer acetate (GA) and those untreated (UT). There was also a lower but significant IL-4 and IL-5 response for GA and UT respectively. 100% of GA and UT patients had a positive antibody response (mean 4230 U/ml and 1774U/ml respectively). In ocrelizumab (OCR) patients, IFN-gamma and IL-2 responses were higher compared to GA and UT patients. Lower but significant IL-5, IL-4, and IL-13 responses were found. B cell immunity was much lower as only 32% showed a positive antibody response (mean 337 U/ml). For patients on sphingosine-1-phosphate receptor (S1PR) modulators, only 6.4% had a positive T cell response even after 3 doses. However, 87% had a positive B cell response (mean 725 U/ml). No relevant change in IL-17, IL-10, or TNF-alpha concentration was observed among the previously mentioned DMT groups despite TNF-alpha levels being elevated in all groups upon SARS-CoV2 Ag challenge. Similar patterns were also seen after the third mRNA dose. Conclusion(s): This study corroborates known data that the T helper cell type 1 response is the main T-cell response to SARS-CoV-2 mRNA vaccines with the highest response seen in OCR patients. A lower T helper cell type 2 response is observed and is variable depending on treatment modalities. This however is not the case for patients on S1PR modulators whose cellular responses were severely diminished.
ABSTRACT
Background: The highly contagious SARS-CoV-2 is mainly transmitted by respiratory droplets and aerosols. Consequently, people are required to wear masks and maintain a social distance to avoid spreading of the virus. Despite the success of the commercially available vaccines, the virus is still uncontained globally. Given the tropism of SARS-CoV-2, a mucosal immune reaction would help to reduce viral shedding and transmission locally. Only seven out of hundreds of ongoing clinical trials are testing the intranasal delivery of a vaccine against COVID-19. Methods: In the current study, we evaluated the immunogenicity of a traditional vaccine platform based on virus-like particles (VLPs) displaying RBD of SARS-CoV-2 for intranasal administration in a murine model. The candidate vaccine platform, CuMVTT -RBD, has been optimized to incorporate a universal T helper cell epitope derived from tetanus-toxin and is self-adjuvanted with TLR7/8 ligands. Results: CuMVTT-RBD vaccine elicited a strong systemic RBD- and spike- IgG and IgA antibodies of high avidity. Local immune response was assessed and our results demonstrate a strong mucosal antibody and plasma cell production in lung tissue. Furthermore, the induced systemic antibodies could efficiently recognize and neutralize different variants of concern (VOCs) of mutated SARS-CoV-2 RBDs. Conclusion: Our data demonstrate that intranasal administration of CuMVTT-RBD induces a protective systemic and local specific antibody response against SARS-CoV-2 and its VOCs.
ABSTRACT
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.
ABSTRACT
Current review presents a brief overview of the immune system dysregulation during acute COVID-19 and illustrates the main alterations in peripheral blood CD4+ T-cell (Th) subsets as well as related target cells. Effects of dendritic cell dysfunction induced by SARS-CoV-2 exhibited decreased expression of cell-surface HLA-DR, CCR7 as well as co-stimulatory molecules CD80 and CD86, suggesting reduced antigen presentation, migratory and activation capacities of peripheral blood dendritic cells. SARS-CoV-2-specific Th cells could be detected as early as days 2–4 post-symptom onset, whereas the prolonged lack of SARS-CoV-2-specific Th cells was associated with severe and/or poor COVID-19 outcome. Firstly, in acute COVID-19 the frequency of Th1 cell was comparable with control levels, but several studies have reported about upregulated inhibitory immune checkpoint receptors and exhaustion-associated molecules (TIM3, PD-1, BTLA, TIGIT etc.) on circulating CD8+ T-cells and NK-cells, whereas the macrophage count was increased in bronchoalveolar lavage (BAL) samples. Next, type 2 immune responses are mediated mainly by Th2 cells, and several studies have revealed a skewing towards dominance of Th2 cell subset in peripheral blood samples from patients with acute COVID-19. Furthermore, the decrease of circulating main Th2 target cells — basophiles and eosinophils — were associated with severe COVID-19, whereas the lung tissue was enriched with mast cells and relevant mediators released during degranulation. Moreover, the frequency of peripheral blood Th17 cells was closely linked to COVID-19 severity, so that low level of Th17 cells was observed in patients with severe COVID-19, but in BAL the relative number of Th17 cells as well as the concentrations of relevant effector cytokines were dramatically increased. It was shown that severe COVID-19 patients vs. healthy control had higher relative numbers of neutrophils if compared, and the majority of patients with COVID-19 had increased frequency and absolute number of immature neutrophils with altered ROS production. Finally, the frequency of Tfh cells was decreased during acute COVID-19 infection. Elevated count of activated Tfh were found as well as the alterations in Tfh cell subsets characterized by decreased “regulatory” Tfh1 cell and increased “pro-inflammatory” Tfh2 as well as Tfh17 cell subsets were revealed. Descriptions of peripheral blood B cells during an acute SARS-CoV-2 infection werev reported as relative B cell lymphopenia with decreased frequency of “naïve” and memory B cell subsets, as well as increased level of CD27hiCD38hiCD24– plasma cell precursors and atypical CD21low B cells. Thus, the emerging evidence suggests that functional alterations occur in all Th cell subsets being linked with loss-of-functions of main Th cell subsets target cells. Furthermore, recovered individuals could suffer from long-term immune dysregulation and other persistent symptoms lasting for many months even after SARS-CoV-2 elimination, a condition referred to as post-acute COVID-19 syndrome.
ABSTRACT
SARS-CoV-2 can cause a decrease in the number of lymphocytes and their functional activity. In patients with COVID-19, especially with a severe course of the disease, a decrease in the quantitative composition of the main populations of lymphocytes is recorded. These indicators do not recover for a long time after recovery. However, it is still not known how long the quantitative and qualitative changes in the composition of lymphocytes will last and whether the severity of the infection affects this process. The aim of our study was to assess the quantitative and qualitative composition of the main populations and subpopulations of lymphocytes in patients with a new coronavirus infection of varying severity. 65 patients with a new coronavirus infection were examined. The average age of the subjects was 47.3±14.5 years. The volunteers were divided into three groups according to the severity of the infection: asymptomatic (n = 21);moderate (n = 32);severe (n = 12). The relative and absolute number of T-lymphocytes (CD3+), T-helper cells (CD3+CD4+), cytotoxic lymphocytes (CD3+CD8+), natural killers (CD3–CD16+CD56+), TNK-lymphocytes (CD3+CD16–CD56+) and B-lymphocytes (CD45+CD19+) were determined. To calculate the percentage of lymphocytes, whole blood was lysed with OPTILYSE C solution (Beckman Coulter, USA) and stained with monoclonal antibodies CD3+-FITC/CD8+-ECD/CD4+PC5/CD16+CD56+PE and CD45+-Pacific Blue/CD19+-PC5 (Beckman Coulter, USA). Cytofluorometry was performed on a flow cytofluorometer “Navios™” (Beckman Coulter, USA). The results of our studies showed that there were no statistically significant changes in the relative and absolute number of immunocompetent cells in asymptomatic patients with a new coronavirus infection, compared with the control group. With an average severity of the disease, a decrease in the relative and absolute content of CD3+ and CD8+ lymphocytes was revealed, these indicators were restored to control values six months after recovery. In patients with severe infection, there was a decrease in the relative and absolute number of T cells and cytotoxic lymphocytes. These values remained significantly below normal for six months and returned to normal only seven to eight months after recovery. Also, the volunteers of this group were found to have a decrease in the number of natural killers and TNK cells. Thus, the data obtained by us indicate that pathological changes concerning the relative and absolute number of the main populations and subpopulations of lymphocytes in patients with COVID-19 depend on the severity of the disease. The number of T-lymphocytes, cytotoxic lymphocytes, natural killer cells, that is, populations of cells that play a crucial role in effective antiviral protection, has been reduced in those who have undergone a new coronavirus infection in moderate and severe form. This information can be useful for expanding methodological approaches to the diagnosis, treatment of a new coronavirus infection, as well as measures for the rehabilitation of those who have suffered it.
ABSTRACT
The new SARS-CoV-2 Omicron variant has more than 15 mutations in the receptor binding domain of the Spike protein enabling increased transmissibility and viral escape from antibodies in vaccinated individuals. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a super-spreader event had robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergent de novo T cell response to non-Spike antigens. Omicron SARS-CoV-2-infected individuals had significantly increased activated SARS-CoV-2 Wild type Spike-specific (vaccine) cytotoxic T cells, activated follicular helper (TFH) cells, functional T cell responses, boosted humoral responses, rapid release of Spike and RBD-specific IgG+ B cell plasmablasts and memory B cells into circulation. Omicron SARS-CoV-2 infected individuals had significantly induced de novo memory T cell responses to non-Spike viral antigens. This concerted T and B cell immunity may provide durable and broad immunity.
ABSTRACT
Introduction Over the last 20 months Sars-CoV-2 research revealed tremendous insights into the pathophysiology resulting in vaccines and first immunomodulatory therapies in an unprecedented short time [1]. However, the patient's individual clinical course is remarkably heterogenous and the effectivity of immunomo-dulatory therapies especially in critically ill patients is still very variable [2]. Therefore,a better understanding of the patients' individual immune response is needed [3]. Methods Unbiased machine learning grouped 323 Covid-19 patients treated at the Klinikum Rechts der Isar ICU into 3 different clusters. For this we queried the ICU electronic files and analyzed relevant clinical features (Fig. 1+2). To delineate biological differences within these clusters, we applied a 14 parameter flow cytometric panel to PBMCs from 27 of these CoV2 ICU patients. Flow data was analyzed using FlowJo and the FlowSOM package for unsupervised clustering (Fig. 3+4). Written informed consent was obtained from all patients and healthy controls. The study was approved by the local ethical review board (Az249/20 S-EB). Results Patients from cluster 1 had above ICU average respiratory function (Fig. 2), reduced liver function and received lower dose catecholamines. Immunologically these patients had significantly higher amount of CD3+CD4+ T helper cells (Fig. 5). Whilst B cell numbers were reduced, they were highly activated (HLA-DR-ordf). Activated monocytes produced high amounts of TNFa. Interestingly, proinflammatory CD14+ HLA-DRlow monocytes were not increased. Cluster 2 contains patients with renal impairment, an increased tendency for bacterial infection and elevated blood lactate levels. Cluster 3 is made up of long-term ICU patients with severely reduced respiratory function and high ECMO-dependency (Fig. 1). These patients had significantly increased ratios of activated innate immune cells. We have detected elevated levels of an interesting population of CD14+ HLA-DRlow monocytes, a well-established player of immune suppression [4], while cytotoxic T cells and B cells were found to be significantly reduced. Conclusion These data provided evidence that clinically defined endotypes of critically ill Covid-19 patients exhibit a distinct immune profile. The immunological differences support our theory that these endotypes might require personalized immunomodulatory therapies to restore the pro-regenerative cell function in ICU Covid-19 populations and improve patient outcome in the future.
ABSTRACT
Study objective - assessment of the humoral and cell-mediated immunity features in COVID-19 convalescents three months after their discharge from the hospital. Material and Methods - The study involved 78 COVID-19 convalescents who, depending on the profile of specific IgM and IgG antibodies to SARS-CoV-2, were divided into three groups. The control group consisted of 50 volunteers. Detection of IgM and IgG in blood serum was performed by ELISA. Determination of CRP concentration was conducted using the immunoturbidimetric assay. To determine the levels of IL-6, a sandwich version of the solid-phase ELISA was employed. Immunophenotyping of lymphocytes was performed via flow cytometry. Results - Of 78 COVID-19 convalescents three months after their discharge from the hospital, 30.8% of them had a profile of specific antibodies IgM(+)IgG(+), 37.2% had IgM(-)IgG(+), and 32.0% were characterized by IgM(-)IgG (-). COVID-19 convalescents with an IgM()IgG(-) profile had the highest levels of NK cells, T helper cells, B lymphocytes (p<0.001) and were characterized by hyperproduction of proinflammatory IL-6 (p<0.001). COVID-19 convalescents with an IgM(+)IgG(+) specific antibody profile were characterized by the highest levels of cytotoxic T lymphocytes (p<0.001). In a COVID-19 convalescent with an IgM(-)IgG(+) specific antibody profile, we observed an increase in the number of lymphocytes expressing late activation/apoptosis molecules (p<0.001). Conclusion - The collected data is of potential importance in clinical practice for developing a prognosis for epidemiological situation development, as well as for planning preventive measures to COVID-19.