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Background & Aim: Amniotic fluid (AF)-derived EVs are currently under investigation for use as anti-inflammatory therapeutics in COVID-19 and COVID-19 long haulers. The dysregulation of the immune response induced by SARS-COV-2 is a key driver of both acute COVID-19 induced lung injury and long term COVID-19 sequela. There is a clear need to identify therapeutics that suppress excessive inflammation and reduce immune cell exhaustion to improve patient short term and long-term outcomes. Amniotic fluid (AF)- derived extracellular vesicles (EVs) have previously been shown to deliver anti-inflammatory and immune-modulatory signals to diverse cellular targets. We aimed to test if AF-EVs carry immune-suppressive molecules and can suppress T-cell immune activation and exhaustion in vitro. Methods, Results & Conclusion(s): The AF-EV biologic tested was derived from AF collected from consenting donors during planned, fullterm cesarean sections. AF was centrifuged and filtered to remove cellular debris and create a product containing AF-EVs and soluble extracellular components. Fluorescent EXODOT analysis was performed to demonstrate the presence of EV markers CD9, CD81, ALIX, and immune suppressive molecule PD-L1. T-cell activation/exhaustion was induced in vitro by treating human peripheral blood mononuclear cells with activation agent PHA for 3 days with the addition of AF-EVs or saline control. Immune activation/exhaustion was measured by flow cytometry to determine the expression of PD-1 on CD3+ T-cells. The AF-EV biologic was characterized to contain EVs with positive expression of CD9, CD81, ALIX, and PL-L1. T-cell activation/exhaustion was upregulated in response to PHA and was significantly reduced by 8% in AF-EV treated T-cells compared to saline control (77.7% vs 85.7%, respectively P<0.05). These findings demonstrate that AF-EVs do express PD-L1, a surface marker that has previously been demonstrated to contribute to exosome-mediated immunosuppression. Furthermore, we confirmed in vitro that AF-EVs suppress T-cell activation/ exhaustion in the presence of a T-cell activation agent. COVID-19 long haulers have been described to have upregulated and pro-longed immune activation and T-cell exhaustion, marked by an increase in PD1+ T-cells. Therefore, this finding serves as a starting point for the development of a potential mechanism of action that may describe AF-EV's therapeutic effect in COVID-19 long hauler patients.Copyright © 2023 International Society for Cell & Gene Therapy
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The pathogenesis of severe coronavirus infection COVID-19 is associated with activation of immune system, cytokine storm, impaired blood clotting, microvascular thrombosis, organ ischemia and multiple organ dysfunction syndrome. The role of various lymphocyte subpopulations in COVID-19 is still debated. The aim of our study was to analyze the subpopulational profile of peripheral blood lymphocytes in COVID-19 patients as compared with healthy donors. The study included 20 COVID-19 patients (11 males and 9 females,) and 26 healthy donors. Average age of the patients was 52 and 56 years, respectively. Clinical examinations were performed by standard laboratory methods. Peripheral blood lymphocytes were isolated in the Ficoll gradient. The cells were stained with antibodies to specific antigens of main lymphocyte populations, endothelial cells, and apoptotic cell markers. The analysis was performed by flow cytometry. The results showed that all patients had elevated C-reactive protein (14- to 35-fold), ferritin (1.2- to 13-fold), D-dimers (1.2- to 90-fold). 55% of men had a decrease in the absolute number of lymphocytes, in women this index was at the low normal limit. Cytometric analysis showed that, among peripheral blood lymphocytes, the proportion of functional cells expressing the CD45 marker ranged from 2 to 12% in 70% of patients, as compared with 80-99% among the donors. The proportion of CD45+ lymphocytes significantly correlated with the level of hemoglobin, but not with the levels of inflammatory biochemical markers. Among the functional lymphocytes of patients, there was a decrease in the proportion of CD3+, CD4+, CD8+T cells, increased proportion of natural killer CD56+ and the apoptotic (AnnexinV+) cell contents, but the proportion of CD19 and HLA-DR+B cells was not changed. Analysis of the lymphocyte (LC) subpopulations that did not express CD45 marker showed that this fraction contained different lymphocyte subsets with reduced expression of CD4, CD8, CD19, CD56 etc. in the blood of patients and donors. Higher percentage of endothelial cells expressing CD62P marker made the difference between patients and donors. Laboratory determination of lymphocyte subsets in blood samples of COVID-19 patients does not reflect the real severity pattern of the disease, thus requiring studies of the CD45-expressing functional cell populations.Copyright © Svirshchevskaya E.V. et al., 2023 The article can be used under the Creative Commons Attribution 4.0 License.
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Assessment of viral load levels in various biological samples taken from the respiratory tract can be an indicator of an ongoing process of active viral replication and may be used to monitor severe respiratory viral infections. The study of the relationship between SARS-CoV-2 viral load and immunological laboratory parameters is an important step in the search for clinical markers of COVID-19. The aim of this research was to quantify viral load in patients with COVID-19 and to identify the relationship between viral load and changes in the parameters of the cellular component of the immune system. A laboratory examination was carried out on 74 patients diagnosed with COVID-19, they were divided into 3 groups based on the severity of the disease: mild, moderate, severe. Total viral load in clinical samples was determined by the number of SARS-CoV-2 RNA copies per 100 copies of the reference RNaseP gene. A comprehensive assessment of the cellular component of the immune system was performed using flow cytometry and direct monoclonal antibodies, and the IL-6, and C-reactive protein concentrations were determined. We revealed a relationship between the development of serious clinical conditions in the patients with COVID-19, and the levels of viral load. High levels of viral RNA in biological samples correlate with main indicators of the T cell component of the immune system associated with disease severity. In a subgroup of patients with an extremely high viral load, strong positive correlations were found between the relative numbers of cytotoxic lymphocytes (CD3+CD8+), activated T lymphocytes (CD3+HLA-DR+), as well as absolute and relative numbers of activated B lymphocytes and NK cells (CD3-CD25+). Laboratory monitoring of the cellular component of the immune system, along with the assessment of viral loads, should improve early assessment of clinical condition in the patients with COVID-19. Changes in expression levels of activation markers on immune cells can be potentially viewed as indicators of recovery during COVID-19.Copyright © Nikitin Yu.V. et al., 2023 The article can be used under the Creative Commons Attribution 4.0 License.
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A 66-year-old male with end-stage liver disease (ESLD) secondary to non-alcoholic fatty liver disease (NAFLD), complicated by hepatocellular carcinoma (HCC), underwent deceased donor liver transplantation from a Coronavirus disease 2019 (COVID-19) positive donor. He presented a month later with fever, diarrhea and pancytopenia which led to hospitalization. The hospital course was notable for respiratory failure, attributed to invasive aspergillosis, as well as a diffuse rash. A bone marrow biopsy revealed hypocellular marrow without specific findings. In the following days, laboratory parameters raised concern for secondary hemophagocytic lymphohistiocytosis (HLH). Clinical concern also grew for solid organ transplant graft-versus-host-disease (SOT-GVHD) based on repeat marrow biopsy with elevated donor-derived CD3+ T cells on chimerism. After, a multidisciplinary discussion, the patient was started on ruxolitinib, in addition to high dose steroids, to address both SOT-GVHD and secondary HLH. Patient developed symptoms concerning for hemorrhagic stroke and was transitioned to comfort care. Although GVHD has been studied extensively in hematopoietic stem cell transplant (HSCT) patients, it is a rare entity in SOT with a lack of guidelines for management. Additionally, whether COVID-19 may play a role in development of SOT-GVDH has not been explored.Copyright © 2023 The Authors
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Objective: To analyze the clinical features of patients with COVID-19 in Chongqing Municipality. Method(s): The clinical data, laboratory tests and chest imaging findings of 153 patients COVID-19 admitted in Chongqing Public Health Medical Center from January 26 to February 5, 2020 were retrospectively reviewed. According to the relevant diagnostic criteria, patients were divided into non-severe group (n=132) and severe group (n=21). The correlation between serum index changes and disease severity was analyzed. Result(s): The proportion of patients with underlying diabetes or chronic respiratory diseases in severe group was significantly higher than that in non-severe group (chi2=11.04 and 6.94, P<0.05). The proportion of symptom-free patients in non-severe group was significantly higher than that in severe group (chi2=4.09, P<0.05). The symptoms of fever, fatigue and muscle soreness in the severe group were more common than those in the non-severe group (chi2=4.40, 14.42 and 22.67, P<0.05). Among the concomitant symptoms, the proportion of cough and shortness of breath in the severe group was higher than that in the non-severe group (chi2=8.46 and 4.80, P<0.05). C-reactive protein and D-Dimer levels were higher in the severe group than those in the non-severe group (Z=-4.39 and -1.96, P<0.05), and the number of CD3+ T lymphocyte cells, CD4+ T lymphocyte cells and CD8+ T lymphocyte cells in the severe group was lower than that in the non-severe group (Z=27.25, 20.60 and 17.36, P<0.05). Compared with the non-severe group, both lungs and the right lung lower lobe were more susceptible to be involved(chi2=9.7123.61, P<0.05). Conclusion(s): There are significant differences in underlying diseases, clinical symptoms, imaging manifestations and laboratory findings between severe and non-severe patients with COVID-19.Copyright © 2020 by the Chinese Medical Association.
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Background: Belarus started developing a vaccine against SARS-CoV- 2 in 2021. The aim of the first stage of investigation was to evaluate the immunogenicity of the vaccine prototypes (VP) in vitro. Method(s): SARS-CoV- 2 strains (n = 7) were isolated using Vero E6 cells, inactivated with beta-propiolactone and purified. Antigens (Ag) were adsorbed on adjuvants: Al(OH)3 (Ag+AH group) or Al3PO4 (Ag+AP group). The single dose of VP (500 ul) was composed of 10 mug of Ag adsorbed on adjuvants (200 mug of Al3+). Blood samples from SARS-CoV- 2 recovered donors (n = 18) and healthy controls having no history of COVID-19 infection (n = 5) were used. Whole blood and Tag-it Violet labeled PBMCs were cultivated with VP, pure Ag, adjuvants (0.25-1 mug of Ag, 20 mug of Al3+ for probe) or pool of peptides, covering sequence of SARS-CoV- 2 N, S, M-proteins (PP), for 6 h and 7 days respectively. INF-gamma production and proliferation of CD3+ T-cells were assayed by FACS. Result(s): Counts of CD3+IFN-gamma+ T cells were 3.14(2.72-5.13)/ 1x105 CD3+ T cells in negative control (NC), and 12.73(10.09-33.95)/ 1x105 CD3+ T cells in specific positive control (PP) (n = 18, p < 0.0001), proving presence of antigen-specific T cells (ASCs) in donor blood. Samples were considered positive for VP and Ag immunogenicity when numbers of CD3+IFN-gamma+ T cells were 1.5 times greater compared with NC. Both VP types (Ag+AP, Ag+AH) and pure SARS-CoV- 2 isolates stimulated the production of INF-gamma by ASCs, responses ranged from 1 to 4 isolates of 7 studied per donor. Immunogenicity of Ag+AP, Ag+AH was confirmed by proliferation assay. Proliferation level was 1.07(0.97-2.38)% in Ag group with no differences from NC (n = 7, p > 0.5). Proliferation was significantly greater in VP groups compared with Ag: 2.47(1.65-2.68)% in Ag+AH, 4.03(2.56-4.61)% in Ag+AP (p = 0.009 and 0.002, respectively), stimulation of T cell was stronger by Ag+AP compared with Ag+AH (p = 0.009, M-U test). Pure adjuvants did not induce T cells response. There was no T-cell stimulation by Ag and VP in samples obtained from COVID-19 negative donors. Conclusion(s): The VP against SARS-CoV- 2 infection composed of inactivated virus adsorbed on Al(OH)3 and Al3PO4 adjuvants has immunogenic properties proven in two different immunological assays. VP stimulated activation and proliferation of ASCs in vitro suggesting this VP can be used for further preclinical in vivo evaluation.
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Objective: To analyze the risk factors of fatal outcome in patients with severe COVID-19. Method(s): The clinical characteristics of 107 patients with severe COVID-19 admitted in Renmin Hospital of Wuhan University from February 12 to March 12, 2020 were retrospectively analyzed. During the hospitalization 49 patients died (fatal group) and 58 patients survived (survival group). The clinical characteristics, baseline laboratory findings were analyzed using R and Python statistical software. The risk factors of fatal outcome in patients with severe COVID-19 were analyzed with multivariate logistic regression. Result(s): Univariate analysis showed that the two groups had statistically significant differences in age, clinical classification, dry cough, dyspnea and laboratory test indicators (P<0.05 or <0.01). The random forest model was used to rank the significance of the statistically significant variables in the univariate analysis, and the selected variables were included in the binary logistic regression model. After stepwise regression analysis, the patient's clinical type, age, neutrophil count, and the proportion of CD3 cells are independent risk factors for death in severe COVID-19 patients. Dry cough is an independent protective factor for the death of severe COVID-19 patients. Conclusion(s): COVID-19 patients with fatal outcome are more likely to have suppressed immune function, secondary infection and inflammatory factor storm. These factors may work together in severe patients, leading to intractable hypoxemia and multiple organ dysfunction and resulting in fatal outcome of patients. The study indicates that timely intervention and treatment measures against above factors may be effective to save the lives of patients with severe COVID-19.Copyright © 2020 by the Chinese Medical Association.
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Objective: To analyze the risk factors of fatal outcome in patients with severe COVID-19. Method(s): The clinical characteristics of 107 patients with severe COVID-19 admitted in Renmin Hospital of Wuhan University from February 12 to March 12, 2020 were retrospectively analyzed. During the hospitalization 49 patients died (fatal group) and 58 patients survived (survival group). The clinical characteristics, baseline laboratory findings were analyzed using R and Python statistical software. The risk factors of fatal outcome in patients with severe COVID-19 were analyzed with multivariate logistic regression. Result(s): Univariate analysis showed that the two groups had statistically significant differences in age, clinical classification, dry cough, dyspnea and laboratory test indicators (P<0.05 or <0.01). The random forest model was used to rank the significance of the statistically significant variables in the univariate analysis, and the selected variables were included in the binary logistic regression model. After stepwise regression analysis, the patient's clinical type, age, neutrophil count, and the proportion of CD3 cells are independent risk factors for death in severe COVID-19 patients. Dry cough is an independent protective factor for the death of severe COVID-19 patients. Conclusion(s): COVID-19 patients with fatal outcome are more likely to have suppressed immune function, secondary infection and inflammatory factor storm. These factors may work together in severe patients, leading to intractable hypoxemia and multiple organ dysfunction and resulting in fatal outcome of patients. The study indicates that timely intervention and treatment measures against above factors may be effective to save the lives of patients with severe COVID-19.Copyright © 2020 by the Chinese Medical Association.
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Objective To study the anti-coronavirus effect of Qingre Xiaoyanning Tablet (), and provide experimental basis for evaluating its prevention and treatment of coronavirus infection. Methods A total of 96 BALB/c mice with half male and half female were randomly divided into control group, model group, Lianhua Qingwen Capsules (, 0.546 g/kg) group and Qingre Xiaoyanning Tablet (8.72, 17.44, 34.89 g/kg) groups with 16 mice in each group. BALB/c mice were infected with ip cyclophosphamide combined with HCoV-229E coronavirus to establish a model of coronavirus infection. The therapeutic effect of Qingre Xiaoyanning Tablet was evaluated by body weight, lung index, viral load, hemagglutination titer and pathological changes in lung tissue of mice;Levels of interleukin-1beta (IL-1beta), IL-4, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and vascular cell adhesion molecule-1 (VCAM-1) in alveolar lavage fluid were detected by ELISA;The proportion of macrophages, lymphocytes (CD3+, CD4+) and NK cells in lung tissue was detected by flow cytometry;Western blotting was used to detect Toll like receptor 4 (TLR4), myeloid differentiation factor 88 (MYD88), inhibitor kappa B kinase-beta (IKK-beta), inhibitor kappa B (IkappaB) and p-IkappaB protein expressions in lung tissue. Results Compared with model group, Qingre Xiaoyanning Tablet significantly increased the body weight of virus infected mice (P < 0.05, 0.01), decreased lung index and hemagglutination titer (P < 0.01), improved lung disease (P < 0.05), and significantly inhibited viral mRNA expression (P < 0.01);TNF-alpha, IL-1 beta and VCAM-1 levels in alveolar lavage fluid were decreased (P < 0.05, 0.01), IFN-gamma level was increased (P < 0.05);The percentage of macrophages was significantly decreased (P < 0.05, 0.01), percentage of CD3+, CD4+ lymphocytes and NK cells was increased (P < 0.01);MYD88, TLR4, IkappaB and IKK-beta protein expressions in lung tissue were significantly down regulated (P < 0.05, 0.01). Conclusion Qingre Xiaoyanning Tablet can inhibit the replication of coronavirus in vivo, reduce inflammatory reaction, protect lung tissue, and has obvious anti-coronavirus effect in vivo. Its mechanism may be related to the regulation of TLR4/MyD88/IKK/IkappaB signal pathway and improving immunity.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.
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Objective: To analyze the clinical features of patients with COVID-19 in Chongqing Municipality. Method(s): The clinical data, laboratory tests and chest imaging findings of 153 patients COVID-19 admitted in Chongqing Public Health Medical Center from January 26 to February 5, 2020 were retrospectively reviewed. According to the relevant diagnostic criteria, patients were divided into non-severe group (n=132) and severe group (n=21). The correlation between serum index changes and disease severity was analyzed. Result(s): The proportion of patients with underlying diabetes or chronic respiratory diseases in severe group was significantly higher than that in non-severe group (chi2=11.04 and 6.94, P<0.05). The proportion of symptom-free patients in non-severe group was significantly higher than that in severe group (chi2=4.09, P<0.05). The symptoms of fever, fatigue and muscle soreness in the severe group were more common than those in the non-severe group (chi2=4.40, 14.42 and 22.67, P<0.05). Among the concomitant symptoms, the proportion of cough and shortness of breath in the severe group was higher than that in the non-severe group (chi2=8.46 and 4.80, P<0.05). C-reactive protein and D-Dimer levels were higher in the severe group than those in the non-severe group (Z=-4.39 and -1.96, P<0.05), and the number of CD3+ T lymphocyte cells, CD4+ T lymphocyte cells and CD8+ T lymphocyte cells in the severe group was lower than that in the non-severe group (Z=27.25, 20.60 and 17.36, P<0.05). Compared with the non-severe group, both lungs and the right lung lower lobe were more susceptible to be involved(chi2=9.7123.61, P<0.05). Conclusion(s): There are significant differences in underlying diseases, clinical symptoms, imaging manifestations and laboratory findings between severe and non-severe patients with COVID-19.Copyright © 2020 by the Chinese Medical Association.
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Background: Although many aspects of the COVID-19 disease have not yet been clarified, dysregulation of the immune system may play a crucial role in the progression of the disease. In this study, the lymphocyte subsets were evaluated in patients with different severities of COVID-19. Material(s) and Method(s): In this prospective study, the frequencies of peripheral lymphocyte subsets (CD3+, CD4+, and CD8+ T cells;CD19+ and CD20+ B cells;CD16+/CD56+ NK cells, and CD4+/CD25+/FOXP3+ regulatory T cells) were evaluated in 67 patients with confirmed COVID-19 on the first day of their admission. Result(s): The mean age of patients was 51.3 +/- 14.8 years. Thirty-two patients (47.8%) were classified as severe cases, and 11 (16.4%) were categorized as critical. The frequencies of blood lymphocytes, CD3+ cells, CD25+FOXP3+ T cells, and absolute count of CD3+ T cells, CD25+FOXP3+ T cells, CD4+ T cells, CD8+ T cells, and CD16+56+ lymphocytes were lower in more severe cases compared to the milder patients. The percentages of lymphocytes, T cells, and NK cells were significantly lower in the deceased patients. (p= 0.002 and p= 0.042, p=0.006, respectively). Conclusion(s): Findings of this cohort study demonstrated that the frequencies of CD4+, CD8+, CD25+FOXP3+ T cells, and NK cells differed in the severe cases of COVID-19. Moreover, lower frequency of T cells and NK cells could be predictors of mortality in these patients.Copyright © 2022, Shaheed Beheshti University of Medical Sciences and Health Services. All rights reserved.
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Background: Infectious diseases have posed a major threat to human survival for centu-ries and can devastate entire populations. Recently, the global outbreak of COVID-19 has increased exponentially, affecting more than 200 countries and millions of lives since the fall of 2019, largely due to the ineffectiveness of existing antiviral therapies. WHO announced it a public health emer-gency of international concern. A significant waiting period in antiviral therapy hindered by the rapid evolution of severe acute respiratory syndrome-coronavirus-2 aggravated the situation ensuing imposition of strict laws (e.g., communal dissociation, international travel restrictions, and mainte-nance of hygiene) that would help in inhibiting further outspread of COVID-19. Ayurveda system of medicine offers a holistic approach to the COVID-19 pandemic. Objective(s): This review aims to highlight the potential of medicinal herbs and Ayurvedic drugs as the remedial approach for viral diseases, such as COVID-19. Method(s): We reviewed the literature from journal publication websites and electronic databases, such as Bentham, Science Direct, Pub Med, Scopus, USFDA, etc. Result(s): The drugs used in the traditional system of medicine have the potential to prevent and cure the infected patient. Ayurvedic therapies are known for regulating immunity and rejuvenation properties that behold much promise in the management of COVID-19 disease. Government of India, Ministry of AYUSH recommends some precautionary fitness measures and an increase in immunity with special reference to respiratory health. Conclusion(s): While there is no medication for COVID-19 as of now, taking preventive measures and boosting body immunity is highly recommended. A number of medicinal plants that play an im-portant role in revitalizing the immune system are easily accessible in home remedies.Copyright © 2023 Bentham Science Publishers.
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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.
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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.
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Overlap between the histopathologic changes of acute rejection and viral myocarditis presents a diagnostic dilemma. A 34 year-old female with a past medical history of postpartum cardiomyopathy and subsequent orthotopic heart transplant in December 2019, presented for routine surveillance heart biopsy seven months post-transplant. Her AlloMap was elevated and AlloSure was uptrending, concerning for rejection. Ten days prior to presentation, she tested positive for COVID-19 via polymerase chain reaction (PCR) testing. Her symptoms were fatigue and mild headache for two weeks prior to diagnosis. She did not seek medical attention for her symptoms and received no COVID-19 specific treatment. Endomyocardial biopsy showed grade 2R acute cellular rejection. Her echocardiogram was unchanged with normal left ventricular ejection fraction and right ventricular function. SARS-CoV-2 levels were measured by PCR of ribonucleic acid (RNA) isolated from the biopsy specimen and were undetectable. The patient was treated with two short courses of high dose prednisone which eventually abated her transplant rejection. The patient remained positive on PCR testing for COVID-19 for the next six months. Chest x-ray and computed tomography for follow up after COVID-19 infection showed no evidence of pulmonary fibrosis or superinfection considering ongoing immunosuppression for rejection. Our patient illustrates a case of concomitant COVID-19 infection and presumed transplant rejection, raising the question of whether the findings seen on immunohistochemistry were truly rejection or instead an elevated immune response due to COVID-19 infection. Given that our patient had a predominance of CD3+ T cells and less CD68+ macrophages (the former being more prominent in acute cellular rejection and the latter being more prominent in COVID-19 myocarditis), we are inclined to believe the former. (Figure Presented).
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SESSION TITLE: Systemic Diseases with Deceptive Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Amyloidosis of the respiratory tract is rare. We present a case of tracheobronchial amyloid presenting as multifactorial cough with syncope. CASE PRESENTATION: The patient is a 65-year-old man with history of hypertension, hyperlipidemia, and allergic rhinitis who presented to the ED after a syncopal event. Two weeks prior, he had a new-onset myalgias and severe persistent cough, not resolving with over-the-counter medications. During a coughing paroxysm, he experienced a brief loss of consciousness. On arrival, his vital signs and physical exam were within normal limits except for Mallampati II, BM of 38.8 kg/m2. Basic laboratory testing was also unremarkable except for troponin T of 251 nl/dL and NT-ProBNP of 1181 pg/mL. NP swab for Sars-CoV-19 (PCR), Influenza A and B were not detected. CT of the chest revealed an area of circumferential mural soft tissue thickening in the left lower lobe bronchi. Cardiac MRI showed an area of subepicardial delayed enhancement, suggestive of myocardial inflammation or edema. Flexible bronchoscopy confirmed that the left lower lobe bronchus and proximal subsegmental bronchi had an infiltrative process with a friable, erythematous irregular mucosal surface. Forceps biopsy sampling and staining with Congo red, sulfate Alcian blue and Trichome stain were positive for amyloid deposits. Immunostain revealed predominantly CD3 positive T-Cells. Mass spectometry showed AL (lamda)-type amyloid deposition. GMS and AFB stains were negative. Telemetry showed 2-3 second pauses, correlated with episodes of cough. DISCUSSION: Amyloidosis is a disorder caused by misfolding of proteins and fibril accumulation in the extracellular space. It can present as a diffuse or localized process to one organ system. Several patterns of lung involvement have been described: nodular pulmonary, diffuse alveolar-septal, cystic, pleural, and tracheobronchial amyloidosis. Tracheobronchial amyloidosis is usually limited and not associated with systemic disease or hematologic malignancy. It can be asymptomatic, or can present with cough, dyspnea or signs of obstruction, including postobstructive pneumonia. Congo Red stained samples reveal green birefringence under polarized light microscopy. Further analysis of proteins usually reveals localized immunoglobulin light chains (AL). Cough syncope is due to increased intrathoracic pressure, decreased venous return and cardiac output, stimulation of baroreceptors, decreased chronotropic response, arterial hypotension and decreased cerebral perfusion. Our patient presented with multifactorial cough (possible viral infection, upper airway cough syndrome, amyloidosis) causing sinus pauses and syncope, on underlying myocarditis. CONCLUSIONS: Amyloid infiltration of the respiratory system is rare, but it should be considered in the differential diagnosis of airway disorders, nodular or cystic lung diseases, and pleural processes. Reference #1: Milani P, Basset M, Russo F, et al. The lung in amyloidosis. Eur Respir Rev 2017;26: 170046 [https://doi.org/10.1183/16000617.0046-2017]. Reference #2: Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996 Feb 15;124(4):407-13. doi: 10.7326/0003-4819-124-4-199602150-00004 Reference #3: Dicpinigaitis PV, Lim L, Farmakidis C. Cough syncope. Respir Med. 2014 Feb;108(2):244-51. doi: 10.1016/j.rmed.2013.10.020. Epub 2013 Nov 5. PMID: 24238768. DISCLOSURES: No relevant relationships by Amarilys Alarcon-Calderon No relevant relationships by Ashokakumar Patel
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The proceedings contain 6 papers. The topics discussed include: a year in the public life of covid-19 and vitamin d: representation in UK news and social media and implications for future health communications;α-linolenic acid metabolism in human CD3+ T cells is dependent on n-6/n-3 ratio and age;associations and effects of anthropometric and body composition parameters on cancer-related fatigue in breast cancer survivors during adjuvant endocrine therapy;improving inpatient assessment of nutritional status using the malnutrition universal screening tool (MUST);dietary supplements, daily nutrient intake, and health-related quality of life among people with myalgic encephalomyelitis/chronic fatigue syndrome;and effect of chia seed (Salvia hispanica L.) consumption on adiposity parameters in rats exposed to cafeteria diet.
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Background: COVID19 and its etiological agent SARS-COV2 may cause a wide spectrum of clinical disease ranging from asymptomatic infection to severe disease and death. Clinical severity of disease has been linked to the variable immune responses to the virus. Identification of markers that distinguish clinically mild from severe disease may be of benefit in predicting disease severity. Design: Analysis of T cells (CD3), three subsets of macrophages (CD11b, CD163, and CD206), PDL1 and viral load in nasopharyngeal swabs of 20 people that were reverse transcriptase polymerase chain reaction positive with mild disease and 20 reverse transcriptase polymerase chain reaction negative controls versus the same variables in 20 lungs from people who died with COVID-19 versus normal aged matched controls was performed. The fatal COVID-19 lung data were stratified into the lung sections with high viral load versus lung sections, often from the same person, where viral involvement was not evident by in situ hybridization. Results: There was a 20X fold increase in the percentage of CD3+ cells in the viral positive nasopharyngeal swabs versus the controls whereas no change was noted in the CD3 count in the lungs of fatal COVID-19 with high viral load. The percentage of cells positive for the macrophage marker CD163 and for PDL1 were equivalent in the mild versus fatal disease samples. There was a significant increase in the number of cells expressing CD11b and CD206 in the fatal lungs with virus compared to the normal lungs;however, these increases were significantly higher in the nasopharyngeal swabs with mild infection. In the fatal COVID-19 lungs without detectable virus, the PDL1, CD11b and CD206 counts were very low, indicating that even in fatal disease the virus was inducing this immune response. Surprisingly, viral load was equivalent in mild versus fatal disease. Conclusions: It is concluded that markedly increased counts of CD3 T cells as well as CD11b and CD206 macrophages can differentiate mild versus fatal COVID-19 which may provide a way to predict clinical outcome by analyzing viral nasopharyngeal swabs for the T cell and macrophage response.
ABSTRACT
Background: SARS-CoV-2 causes diffuse alveolar damage, lymphocyte infiltration in the lungs and a cytokine storm. In this study we examined inflammatory cell infiltrates in the lungs of patients with COVID-19. Design: Eighteen COVID-19 autopsy cases (COVID group), 9 non-COVID cases with diffuse alveolar damage (DAD, non-COVID group), and eleven controls without lung diseases were included. Immunostainings for CD3, CD4, CD8, CD68 and broad-spectrum keratins were performed. Results: The average age of COVID-19 patients was 64.4±2.1 years. The most common co-morbidities were hypertension (12/17, 70.6%), diabetes mellitus (9/17, 52.9%) and chronic kidney disease (3/17, 17.6%). The survival duration of 17 patients with available clinical information was 21.2 ± 3.4 days (range 7-53 days) after onset of symptoms. Patients younger than 67 years old (namely young patients thereafter, N=9) survived 26.4 ± 5.9 days after onset of symptoms, which was significantly longer than those greater than 67 years old (namely older patients thereafter, 15.2 ± 1.4 days, N=8, P<0.05). The younger patients had significantly lower platelet counts (107.7 ± 33.2 x 109/L, N=8) than the older ones (224.6 ± 42.4 x 109/L, N=8, P<0.05). Conversely, the younger patients had much higher absolute lymphocyte counts (1.5 ± 0.4 x 109/L, N=7) than the older ones (0.7 ± 0.1 x 109/L, N=8, P<0.05). Interestingly, the patients with low platelet counts (<100 x 109/L) survived longer than those with higher platelet counts (P<0.05). Patients with high troponin levels (>0.2 ng/ml) had shorter survival duration after onset of symptoms (16.8 ± 1.9 days) than those with low troponin levels (30.8 ± 8.0 days, P<0.05). Patients with macrophages >130/HPF, CD3+ T cells >145/HPF, CD8+ T cells <30/HPF and CD8+/CD4+ ratio<1 had a shorter survival time compared to those with macrophages <130/HPF, CD3+ T cells <145/HPF, CD8+ T cells >30/HPF and CD8+/CD4+ ratio>1, respectively. Conclusions: Patients' age > 67 years, blood troponin levels >0.2 ng/ml, platelet count >100 x 109/L, lung macrophages >130/HPF, CD3+ T cells >145/HPF, CD8+ T cells <30/HPF, and CD8/CD4 ratio <1 were associated with shorter survival duration after onset of symptoms.